Dietary phytonutrients as alternatives -to-antibiotics in ... · hormonal messengers. Hormesis: is...
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Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals: Mode of action in modulating cross-talks among immunity, disease resistance and gut microbiota LILLEHOJ, HYUN ANIMAL BIOSCIENCES AND BIOTECHNOLOGY LABORATORY BELTSVILLE AGRICULTURAL RESEARCH CENTER, U.S. DEPARTMENT OF AGRICULTURE, AGRICULTURAL RESEARCH SERVICE BELTSVILLE, MD, USA 2 nd International Symposium on Alternatives to Antibiotics, OIE, Paris, France,12-15 December 2016
Transcript of Dietary phytonutrients as alternatives -to-antibiotics in ... · hormonal messengers. Hormesis: is...
Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiotaL I L L E H O J H Y U NA N I M A L B I O S C I E N C E S A N D B I O T E C H N O L O G Y L A B O R A T O R YB E LT S V I L L E A G R I C U LT U R A L R E S E A R C H C E N T E R U S D E PA R T M E N T O F A G R I C U LT U R E A G R I C U LT U R A L R E S E A R C H S E R V I C EB E LT S V I L L E M D U S A
2nd International Symposium on Alternatives to Antibiotics OIE Paris France12-15 December 2016
2nd International Symposium on Alternatives to Antibiotics OIE Paris France12-15 December 2016
Consumers want a food system that assures food is safe affordable healthful and sustainable
Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
Signs of poor gut health
Dibner J 2010 Int Coccidiosis Conf 10 Guangdong China
AntibioticsDiet
DrugsDiseaseStress
Furness JB 2013 Nature Reviews GastroenterologyHepatology
Bischoff BMC Medicine 2011 924
Why do we want healthy gut
Structural Intestinal Integrity-Effective Digestion and
Absorption of Food
Balanced and Stable Intestinal Microbiota
Balanced Immune Response-Absence of GI Illness
Dysbiosis and subclinical enteritis
Inflammation and acute phase immune response
Oxidative and osmotic dysfunction
Gut barrier dysfunction
Impaired nutrient synthesis (vitamins minerals SCFA)impaired energy metabolism
Low-level effect of antibiotic growth promoters on body weight gains in broilers
(Oh ST and Lillehoj HS 2017)
Mechanisms of Antibiotic Growth Promoters (AGP)
1 Anti-microbial2 Reduce subclinical infections3 Reduce microbial use of nutrients4 Reduce growth-depressing microbial metabolites5 Enhance uptake of nutrients due to histologically thinner gut
in antibiotic-treated animals6 Reduce pro-inflammatory cytokineschemokines7 In germ-free mice antibiotics increase in adiposity8 In human newborns antibiotics is associated with obesity
AGP
Competitive exclusionEnteric pathogen
Mucosal protectionInnate and adaptive immunity
Energy efficiency
Maintenance
Beneficial effects of antibiotic alternatives
Affect GI mucosa
Stimulates enzyme secretion
Improve microbial flora
Nutrient digestion
GrowthReproduction
Report of the meeting of the OIE AD HOC Group on prioritization of diseases for which vaccines could reduce antimicrobial use in animals Paris April 21-23 2015
Bacitracin GP NE CO
Virginiamycin GP NE
Coccidiosis and Necrotic Enteritis
Lillehoj HS 2015 Avian Coccidiosis as a prototype intestinal diseases In Intestinal Health Key to maximize growth performance in livestock edited by Theo Niewold Wagenigen Academic The Netherlands Pp 71-116
Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology 45313-316
Antibiotic alternatives-Mechanisms
Gadde U Lillehoj H 2017 Antibiotic Alternatives- A Review Animal Health Research Reviews In press
Essential oils key in fight against antibiotic useFeb 4 2016 1227 1
Essential oils are a key solution to an alternative for antibiotic growth promoters (AGPs) this was shown by research carried out by US food giant Cargill But what do essential oils achieve that other non-medicated feed additives donrsquot
Carbohydrate = 250 gramsProtein =100 gramsFat = 60 gramPhytonutrients =15 grams
Walsh et al 2007
ncbinlmnihgovPubmed
Function of Phytochemicals
1 Anti-oxidants carotenoids polyphenols2 Stimulates innate immunity3 Enhance adaptive (memory) immunity tumeric4 Stimulate enzymes Indole from cabbage5 Anti-bacterial allicin from garlic6 Promote beneficial bacterial growth7 Hormonal activity isoflavones from soy8 Physically block pathogen binding Proanthocyanidins9 Serve as signal transduction agents 10 Epigenetic regulation (Isoflavone tumeric)
Phytonutrientsphytochemicals Broad name for a wide variety of compounds produced by plants found in fruits vegetables beans grains and other plants
Furness 2016
Phytochemicals act on receptors on entero-endocrine cells to release hormonal messengers
Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
Son T Camandola S and Mattson M 2008 Hormetic dietary phytochemicals Neuromolecular Med 2008 10236-246
Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
Li Lillehoj et al 2010 Avian Pathology 39255 Li Lillehoj et al 2010 Avian Pathology 39247 Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology In press
Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
19
Kim DK Lillehoj HS 2014 Transcriptional profiles of host-pathogen responses to necrotic enteritis and differential regulation of immune genes in two inbreed chicken lines showing disparate disease susceptibility PLoS ONE 9(12)e114960
Avian Coccidiosis
Coccidiosis are ubiquitous they are present wherever chickens arereared (traditional industrial label or organicbio farms) Nine speciesof Eimeria have been described in chicken
Balance of Th17 and Treg cells in Coccidiosis
Th17 and Treg cells have opposite actions on intestinal immunity
Treg cells suppress a variety of physiological and
pathological immune responses in the intestine
Th17 cells play a key role in intestinal inflammation
through induction of pro-inflammatory cytokines
Dendritic cells (APC) present the antigen to the T cells
Naiumlve CD4+ T cells differentiate into either Th17 or Treg
once in contact with dendritic cells
In gut immune systemhellip
IL-17 as a potential therapeutic target of coccidiosisIL-17
bull is pro-inflammatory cytokine produced by Th17 cells
bull induces various pro-inflammatory cytokines and
mediates inflammatory response
Administration of IL-17A neutralizing antibody induce
- Enhanced weight gain
- Reduced oocyst shedding
- Increased heterophil infiltration
- Reduction of cecal lesion
- Inhibition of E tenella schizont and merozoite development
Del Cacho et al 2014 Zhang et al 2013
Kim WH Jeong J Park AR Yim D Kim S Chang HH Yang SH Kim DH Lillehoj HS Min W 2014 Downregulation of chicken interleukin-17 receptor A during Eimeria infection Infect Immun 82(9)3845-54
Flow diagram for screening immunoactive phytochemicals
Disease challenge
Macrophage activation
Lymphocyte stimulation
Cytokine Tumor cytotoxicity Direct killing of pathogens
Select synergistic plants
Nutrigenomics
In vitro screening
In vivo feeding trial
Randomized Performance analysis in commercial broilers
In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
5 ppmcarvacrol
3 ppmcinnamaldehyde
2 ppmCapsicum oleor
23
246
625198
3126
48
156
31
Primary infectionE Maxima
Secondary infectionE Maxima
Up regulated Down regulated
Kim DK Lillehoj HS Lee S H Jang S and Bravo D 2010 High-Throughput Gene Expression Analysis of Intraepithelial Lymphocytes Following dietary Carvacrol Cinnamaldehyde or Capsicum Oleoresin Poultry Science 8968-81Kim DK Lillehoj HS Min WG Kim CH Hong YH and Lillehoj EP 2011 PlosOne V6e27712
NUTRIGENOMICS to identify 3 phytonutrient combination that reduced negative effects of avian coccidiosis
From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
Phytochemical doses that we used were not cytotoxic to pathogens
Dietary effects of phytonutrients on coccidiosis
Lee S H Kim Duk Kyung Bravo D Lillehoj HS 2010 Journal Poultry Science 4789-95
Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokinetranscripts and mitigated gut damage due to necrotic enteritis
Lee SH et al Lillehoj HS Bravo DM 2013 Dietary supplementation of young broiler chickens with Capsicum and turmeric oleoresins increases resistance to necrotic enteritis Br J Nutr110(5)840-7
IL-8
LITAF
TL1A
IL-17
IL-17F
Garlic effects in vitro
Kim DK Lillehoj HS Lee SH Lillehoj EP Bravo D 2013 Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites Br J Nutr 109(1)76-88
a
b
a
460
480
500
520
540
560
580
600
Non-infected Control Garlicon 40
Control E acervulina infected
Body
wei
ght
gai
n (
g)
BW gain
a
b
00
05
10
15
20
25
30
Control Garlicon 40
Oocy
sts
(X10
8 )
Oocysts
b
a
0
02
04
06
08
1
Control Garlicon 40
Ab r
esponse
to p
rofilin
(O
D
450n
m)
Ab-Profilin
In vivo dietary effects of Garlic
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
2nd International Symposium on Alternatives to Antibiotics OIE Paris France12-15 December 2016
Consumers want a food system that assures food is safe affordable healthful and sustainable
Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
Signs of poor gut health
Dibner J 2010 Int Coccidiosis Conf 10 Guangdong China
AntibioticsDiet
DrugsDiseaseStress
Furness JB 2013 Nature Reviews GastroenterologyHepatology
Bischoff BMC Medicine 2011 924
Why do we want healthy gut
Structural Intestinal Integrity-Effective Digestion and
Absorption of Food
Balanced and Stable Intestinal Microbiota
Balanced Immune Response-Absence of GI Illness
Dysbiosis and subclinical enteritis
Inflammation and acute phase immune response
Oxidative and osmotic dysfunction
Gut barrier dysfunction
Impaired nutrient synthesis (vitamins minerals SCFA)impaired energy metabolism
Low-level effect of antibiotic growth promoters on body weight gains in broilers
(Oh ST and Lillehoj HS 2017)
Mechanisms of Antibiotic Growth Promoters (AGP)
1 Anti-microbial2 Reduce subclinical infections3 Reduce microbial use of nutrients4 Reduce growth-depressing microbial metabolites5 Enhance uptake of nutrients due to histologically thinner gut
in antibiotic-treated animals6 Reduce pro-inflammatory cytokineschemokines7 In germ-free mice antibiotics increase in adiposity8 In human newborns antibiotics is associated with obesity
AGP
Competitive exclusionEnteric pathogen
Mucosal protectionInnate and adaptive immunity
Energy efficiency
Maintenance
Beneficial effects of antibiotic alternatives
Affect GI mucosa
Stimulates enzyme secretion
Improve microbial flora
Nutrient digestion
GrowthReproduction
Report of the meeting of the OIE AD HOC Group on prioritization of diseases for which vaccines could reduce antimicrobial use in animals Paris April 21-23 2015
Bacitracin GP NE CO
Virginiamycin GP NE
Coccidiosis and Necrotic Enteritis
Lillehoj HS 2015 Avian Coccidiosis as a prototype intestinal diseases In Intestinal Health Key to maximize growth performance in livestock edited by Theo Niewold Wagenigen Academic The Netherlands Pp 71-116
Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology 45313-316
Antibiotic alternatives-Mechanisms
Gadde U Lillehoj H 2017 Antibiotic Alternatives- A Review Animal Health Research Reviews In press
Essential oils key in fight against antibiotic useFeb 4 2016 1227 1
Essential oils are a key solution to an alternative for antibiotic growth promoters (AGPs) this was shown by research carried out by US food giant Cargill But what do essential oils achieve that other non-medicated feed additives donrsquot
Carbohydrate = 250 gramsProtein =100 gramsFat = 60 gramPhytonutrients =15 grams
Walsh et al 2007
ncbinlmnihgovPubmed
Function of Phytochemicals
1 Anti-oxidants carotenoids polyphenols2 Stimulates innate immunity3 Enhance adaptive (memory) immunity tumeric4 Stimulate enzymes Indole from cabbage5 Anti-bacterial allicin from garlic6 Promote beneficial bacterial growth7 Hormonal activity isoflavones from soy8 Physically block pathogen binding Proanthocyanidins9 Serve as signal transduction agents 10 Epigenetic regulation (Isoflavone tumeric)
Phytonutrientsphytochemicals Broad name for a wide variety of compounds produced by plants found in fruits vegetables beans grains and other plants
Furness 2016
Phytochemicals act on receptors on entero-endocrine cells to release hormonal messengers
Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
Son T Camandola S and Mattson M 2008 Hormetic dietary phytochemicals Neuromolecular Med 2008 10236-246
Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
Li Lillehoj et al 2010 Avian Pathology 39255 Li Lillehoj et al 2010 Avian Pathology 39247 Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology In press
Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
19
Kim DK Lillehoj HS 2014 Transcriptional profiles of host-pathogen responses to necrotic enteritis and differential regulation of immune genes in two inbreed chicken lines showing disparate disease susceptibility PLoS ONE 9(12)e114960
Avian Coccidiosis
Coccidiosis are ubiquitous they are present wherever chickens arereared (traditional industrial label or organicbio farms) Nine speciesof Eimeria have been described in chicken
Balance of Th17 and Treg cells in Coccidiosis
Th17 and Treg cells have opposite actions on intestinal immunity
Treg cells suppress a variety of physiological and
pathological immune responses in the intestine
Th17 cells play a key role in intestinal inflammation
through induction of pro-inflammatory cytokines
Dendritic cells (APC) present the antigen to the T cells
Naiumlve CD4+ T cells differentiate into either Th17 or Treg
once in contact with dendritic cells
In gut immune systemhellip
IL-17 as a potential therapeutic target of coccidiosisIL-17
bull is pro-inflammatory cytokine produced by Th17 cells
bull induces various pro-inflammatory cytokines and
mediates inflammatory response
Administration of IL-17A neutralizing antibody induce
- Enhanced weight gain
- Reduced oocyst shedding
- Increased heterophil infiltration
- Reduction of cecal lesion
- Inhibition of E tenella schizont and merozoite development
Del Cacho et al 2014 Zhang et al 2013
Kim WH Jeong J Park AR Yim D Kim S Chang HH Yang SH Kim DH Lillehoj HS Min W 2014 Downregulation of chicken interleukin-17 receptor A during Eimeria infection Infect Immun 82(9)3845-54
Flow diagram for screening immunoactive phytochemicals
Disease challenge
Macrophage activation
Lymphocyte stimulation
Cytokine Tumor cytotoxicity Direct killing of pathogens
Select synergistic plants
Nutrigenomics
In vitro screening
In vivo feeding trial
Randomized Performance analysis in commercial broilers
In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
5 ppmcarvacrol
3 ppmcinnamaldehyde
2 ppmCapsicum oleor
23
246
625198
3126
48
156
31
Primary infectionE Maxima
Secondary infectionE Maxima
Up regulated Down regulated
Kim DK Lillehoj HS Lee S H Jang S and Bravo D 2010 High-Throughput Gene Expression Analysis of Intraepithelial Lymphocytes Following dietary Carvacrol Cinnamaldehyde or Capsicum Oleoresin Poultry Science 8968-81Kim DK Lillehoj HS Min WG Kim CH Hong YH and Lillehoj EP 2011 PlosOne V6e27712
NUTRIGENOMICS to identify 3 phytonutrient combination that reduced negative effects of avian coccidiosis
From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
Phytochemical doses that we used were not cytotoxic to pathogens
Dietary effects of phytonutrients on coccidiosis
Lee S H Kim Duk Kyung Bravo D Lillehoj HS 2010 Journal Poultry Science 4789-95
Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokinetranscripts and mitigated gut damage due to necrotic enteritis
Lee SH et al Lillehoj HS Bravo DM 2013 Dietary supplementation of young broiler chickens with Capsicum and turmeric oleoresins increases resistance to necrotic enteritis Br J Nutr110(5)840-7
IL-8
LITAF
TL1A
IL-17
IL-17F
Garlic effects in vitro
Kim DK Lillehoj HS Lee SH Lillehoj EP Bravo D 2013 Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites Br J Nutr 109(1)76-88
a
b
a
460
480
500
520
540
560
580
600
Non-infected Control Garlicon 40
Control E acervulina infected
Body
wei
ght
gai
n (
g)
BW gain
a
b
00
05
10
15
20
25
30
Control Garlicon 40
Oocy
sts
(X10
8 )
Oocysts
b
a
0
02
04
06
08
1
Control Garlicon 40
Ab r
esponse
to p
rofilin
(O
D
450n
m)
Ab-Profilin
In vivo dietary effects of Garlic
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
Consumers want a food system that assures food is safe affordable healthful and sustainable
Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
Signs of poor gut health
Dibner J 2010 Int Coccidiosis Conf 10 Guangdong China
AntibioticsDiet
DrugsDiseaseStress
Furness JB 2013 Nature Reviews GastroenterologyHepatology
Bischoff BMC Medicine 2011 924
Why do we want healthy gut
Structural Intestinal Integrity-Effective Digestion and
Absorption of Food
Balanced and Stable Intestinal Microbiota
Balanced Immune Response-Absence of GI Illness
Dysbiosis and subclinical enteritis
Inflammation and acute phase immune response
Oxidative and osmotic dysfunction
Gut barrier dysfunction
Impaired nutrient synthesis (vitamins minerals SCFA)impaired energy metabolism
Low-level effect of antibiotic growth promoters on body weight gains in broilers
(Oh ST and Lillehoj HS 2017)
Mechanisms of Antibiotic Growth Promoters (AGP)
1 Anti-microbial2 Reduce subclinical infections3 Reduce microbial use of nutrients4 Reduce growth-depressing microbial metabolites5 Enhance uptake of nutrients due to histologically thinner gut
in antibiotic-treated animals6 Reduce pro-inflammatory cytokineschemokines7 In germ-free mice antibiotics increase in adiposity8 In human newborns antibiotics is associated with obesity
AGP
Competitive exclusionEnteric pathogen
Mucosal protectionInnate and adaptive immunity
Energy efficiency
Maintenance
Beneficial effects of antibiotic alternatives
Affect GI mucosa
Stimulates enzyme secretion
Improve microbial flora
Nutrient digestion
GrowthReproduction
Report of the meeting of the OIE AD HOC Group on prioritization of diseases for which vaccines could reduce antimicrobial use in animals Paris April 21-23 2015
Bacitracin GP NE CO
Virginiamycin GP NE
Coccidiosis and Necrotic Enteritis
Lillehoj HS 2015 Avian Coccidiosis as a prototype intestinal diseases In Intestinal Health Key to maximize growth performance in livestock edited by Theo Niewold Wagenigen Academic The Netherlands Pp 71-116
Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology 45313-316
Antibiotic alternatives-Mechanisms
Gadde U Lillehoj H 2017 Antibiotic Alternatives- A Review Animal Health Research Reviews In press
Essential oils key in fight against antibiotic useFeb 4 2016 1227 1
Essential oils are a key solution to an alternative for antibiotic growth promoters (AGPs) this was shown by research carried out by US food giant Cargill But what do essential oils achieve that other non-medicated feed additives donrsquot
Carbohydrate = 250 gramsProtein =100 gramsFat = 60 gramPhytonutrients =15 grams
Walsh et al 2007
ncbinlmnihgovPubmed
Function of Phytochemicals
1 Anti-oxidants carotenoids polyphenols2 Stimulates innate immunity3 Enhance adaptive (memory) immunity tumeric4 Stimulate enzymes Indole from cabbage5 Anti-bacterial allicin from garlic6 Promote beneficial bacterial growth7 Hormonal activity isoflavones from soy8 Physically block pathogen binding Proanthocyanidins9 Serve as signal transduction agents 10 Epigenetic regulation (Isoflavone tumeric)
Phytonutrientsphytochemicals Broad name for a wide variety of compounds produced by plants found in fruits vegetables beans grains and other plants
Furness 2016
Phytochemicals act on receptors on entero-endocrine cells to release hormonal messengers
Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
Son T Camandola S and Mattson M 2008 Hormetic dietary phytochemicals Neuromolecular Med 2008 10236-246
Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
Li Lillehoj et al 2010 Avian Pathology 39255 Li Lillehoj et al 2010 Avian Pathology 39247 Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology In press
Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
19
Kim DK Lillehoj HS 2014 Transcriptional profiles of host-pathogen responses to necrotic enteritis and differential regulation of immune genes in two inbreed chicken lines showing disparate disease susceptibility PLoS ONE 9(12)e114960
Avian Coccidiosis
Coccidiosis are ubiquitous they are present wherever chickens arereared (traditional industrial label or organicbio farms) Nine speciesof Eimeria have been described in chicken
Balance of Th17 and Treg cells in Coccidiosis
Th17 and Treg cells have opposite actions on intestinal immunity
Treg cells suppress a variety of physiological and
pathological immune responses in the intestine
Th17 cells play a key role in intestinal inflammation
through induction of pro-inflammatory cytokines
Dendritic cells (APC) present the antigen to the T cells
Naiumlve CD4+ T cells differentiate into either Th17 or Treg
once in contact with dendritic cells
In gut immune systemhellip
IL-17 as a potential therapeutic target of coccidiosisIL-17
bull is pro-inflammatory cytokine produced by Th17 cells
bull induces various pro-inflammatory cytokines and
mediates inflammatory response
Administration of IL-17A neutralizing antibody induce
- Enhanced weight gain
- Reduced oocyst shedding
- Increased heterophil infiltration
- Reduction of cecal lesion
- Inhibition of E tenella schizont and merozoite development
Del Cacho et al 2014 Zhang et al 2013
Kim WH Jeong J Park AR Yim D Kim S Chang HH Yang SH Kim DH Lillehoj HS Min W 2014 Downregulation of chicken interleukin-17 receptor A during Eimeria infection Infect Immun 82(9)3845-54
Flow diagram for screening immunoactive phytochemicals
Disease challenge
Macrophage activation
Lymphocyte stimulation
Cytokine Tumor cytotoxicity Direct killing of pathogens
Select synergistic plants
Nutrigenomics
In vitro screening
In vivo feeding trial
Randomized Performance analysis in commercial broilers
In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
5 ppmcarvacrol
3 ppmcinnamaldehyde
2 ppmCapsicum oleor
23
246
625198
3126
48
156
31
Primary infectionE Maxima
Secondary infectionE Maxima
Up regulated Down regulated
Kim DK Lillehoj HS Lee S H Jang S and Bravo D 2010 High-Throughput Gene Expression Analysis of Intraepithelial Lymphocytes Following dietary Carvacrol Cinnamaldehyde or Capsicum Oleoresin Poultry Science 8968-81Kim DK Lillehoj HS Min WG Kim CH Hong YH and Lillehoj EP 2011 PlosOne V6e27712
NUTRIGENOMICS to identify 3 phytonutrient combination that reduced negative effects of avian coccidiosis
From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
Phytochemical doses that we used were not cytotoxic to pathogens
Dietary effects of phytonutrients on coccidiosis
Lee S H Kim Duk Kyung Bravo D Lillehoj HS 2010 Journal Poultry Science 4789-95
Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokinetranscripts and mitigated gut damage due to necrotic enteritis
Lee SH et al Lillehoj HS Bravo DM 2013 Dietary supplementation of young broiler chickens with Capsicum and turmeric oleoresins increases resistance to necrotic enteritis Br J Nutr110(5)840-7
IL-8
LITAF
TL1A
IL-17
IL-17F
Garlic effects in vitro
Kim DK Lillehoj HS Lee SH Lillehoj EP Bravo D 2013 Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites Br J Nutr 109(1)76-88
a
b
a
460
480
500
520
540
560
580
600
Non-infected Control Garlicon 40
Control E acervulina infected
Body
wei
ght
gai
n (
g)
BW gain
a
b
00
05
10
15
20
25
30
Control Garlicon 40
Oocy
sts
(X10
8 )
Oocysts
b
a
0
02
04
06
08
1
Control Garlicon 40
Ab r
esponse
to p
rofilin
(O
D
450n
m)
Ab-Profilin
In vivo dietary effects of Garlic
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
Signs of poor gut health
Dibner J 2010 Int Coccidiosis Conf 10 Guangdong China
AntibioticsDiet
DrugsDiseaseStress
Furness JB 2013 Nature Reviews GastroenterologyHepatology
Bischoff BMC Medicine 2011 924
Why do we want healthy gut
Structural Intestinal Integrity-Effective Digestion and
Absorption of Food
Balanced and Stable Intestinal Microbiota
Balanced Immune Response-Absence of GI Illness
Dysbiosis and subclinical enteritis
Inflammation and acute phase immune response
Oxidative and osmotic dysfunction
Gut barrier dysfunction
Impaired nutrient synthesis (vitamins minerals SCFA)impaired energy metabolism
Low-level effect of antibiotic growth promoters on body weight gains in broilers
(Oh ST and Lillehoj HS 2017)
Mechanisms of Antibiotic Growth Promoters (AGP)
1 Anti-microbial2 Reduce subclinical infections3 Reduce microbial use of nutrients4 Reduce growth-depressing microbial metabolites5 Enhance uptake of nutrients due to histologically thinner gut
in antibiotic-treated animals6 Reduce pro-inflammatory cytokineschemokines7 In germ-free mice antibiotics increase in adiposity8 In human newborns antibiotics is associated with obesity
AGP
Competitive exclusionEnteric pathogen
Mucosal protectionInnate and adaptive immunity
Energy efficiency
Maintenance
Beneficial effects of antibiotic alternatives
Affect GI mucosa
Stimulates enzyme secretion
Improve microbial flora
Nutrient digestion
GrowthReproduction
Report of the meeting of the OIE AD HOC Group on prioritization of diseases for which vaccines could reduce antimicrobial use in animals Paris April 21-23 2015
Bacitracin GP NE CO
Virginiamycin GP NE
Coccidiosis and Necrotic Enteritis
Lillehoj HS 2015 Avian Coccidiosis as a prototype intestinal diseases In Intestinal Health Key to maximize growth performance in livestock edited by Theo Niewold Wagenigen Academic The Netherlands Pp 71-116
Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology 45313-316
Antibiotic alternatives-Mechanisms
Gadde U Lillehoj H 2017 Antibiotic Alternatives- A Review Animal Health Research Reviews In press
Essential oils key in fight against antibiotic useFeb 4 2016 1227 1
Essential oils are a key solution to an alternative for antibiotic growth promoters (AGPs) this was shown by research carried out by US food giant Cargill But what do essential oils achieve that other non-medicated feed additives donrsquot
Carbohydrate = 250 gramsProtein =100 gramsFat = 60 gramPhytonutrients =15 grams
Walsh et al 2007
ncbinlmnihgovPubmed
Function of Phytochemicals
1 Anti-oxidants carotenoids polyphenols2 Stimulates innate immunity3 Enhance adaptive (memory) immunity tumeric4 Stimulate enzymes Indole from cabbage5 Anti-bacterial allicin from garlic6 Promote beneficial bacterial growth7 Hormonal activity isoflavones from soy8 Physically block pathogen binding Proanthocyanidins9 Serve as signal transduction agents 10 Epigenetic regulation (Isoflavone tumeric)
Phytonutrientsphytochemicals Broad name for a wide variety of compounds produced by plants found in fruits vegetables beans grains and other plants
Furness 2016
Phytochemicals act on receptors on entero-endocrine cells to release hormonal messengers
Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
Son T Camandola S and Mattson M 2008 Hormetic dietary phytochemicals Neuromolecular Med 2008 10236-246
Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
Li Lillehoj et al 2010 Avian Pathology 39255 Li Lillehoj et al 2010 Avian Pathology 39247 Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology In press
Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
19
Kim DK Lillehoj HS 2014 Transcriptional profiles of host-pathogen responses to necrotic enteritis and differential regulation of immune genes in two inbreed chicken lines showing disparate disease susceptibility PLoS ONE 9(12)e114960
Avian Coccidiosis
Coccidiosis are ubiquitous they are present wherever chickens arereared (traditional industrial label or organicbio farms) Nine speciesof Eimeria have been described in chicken
Balance of Th17 and Treg cells in Coccidiosis
Th17 and Treg cells have opposite actions on intestinal immunity
Treg cells suppress a variety of physiological and
pathological immune responses in the intestine
Th17 cells play a key role in intestinal inflammation
through induction of pro-inflammatory cytokines
Dendritic cells (APC) present the antigen to the T cells
Naiumlve CD4+ T cells differentiate into either Th17 or Treg
once in contact with dendritic cells
In gut immune systemhellip
IL-17 as a potential therapeutic target of coccidiosisIL-17
bull is pro-inflammatory cytokine produced by Th17 cells
bull induces various pro-inflammatory cytokines and
mediates inflammatory response
Administration of IL-17A neutralizing antibody induce
- Enhanced weight gain
- Reduced oocyst shedding
- Increased heterophil infiltration
- Reduction of cecal lesion
- Inhibition of E tenella schizont and merozoite development
Del Cacho et al 2014 Zhang et al 2013
Kim WH Jeong J Park AR Yim D Kim S Chang HH Yang SH Kim DH Lillehoj HS Min W 2014 Downregulation of chicken interleukin-17 receptor A during Eimeria infection Infect Immun 82(9)3845-54
Flow diagram for screening immunoactive phytochemicals
Disease challenge
Macrophage activation
Lymphocyte stimulation
Cytokine Tumor cytotoxicity Direct killing of pathogens
Select synergistic plants
Nutrigenomics
In vitro screening
In vivo feeding trial
Randomized Performance analysis in commercial broilers
In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
5 ppmcarvacrol
3 ppmcinnamaldehyde
2 ppmCapsicum oleor
23
246
625198
3126
48
156
31
Primary infectionE Maxima
Secondary infectionE Maxima
Up regulated Down regulated
Kim DK Lillehoj HS Lee S H Jang S and Bravo D 2010 High-Throughput Gene Expression Analysis of Intraepithelial Lymphocytes Following dietary Carvacrol Cinnamaldehyde or Capsicum Oleoresin Poultry Science 8968-81Kim DK Lillehoj HS Min WG Kim CH Hong YH and Lillehoj EP 2011 PlosOne V6e27712
NUTRIGENOMICS to identify 3 phytonutrient combination that reduced negative effects of avian coccidiosis
From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
Phytochemical doses that we used were not cytotoxic to pathogens
Dietary effects of phytonutrients on coccidiosis
Lee S H Kim Duk Kyung Bravo D Lillehoj HS 2010 Journal Poultry Science 4789-95
Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokinetranscripts and mitigated gut damage due to necrotic enteritis
Lee SH et al Lillehoj HS Bravo DM 2013 Dietary supplementation of young broiler chickens with Capsicum and turmeric oleoresins increases resistance to necrotic enteritis Br J Nutr110(5)840-7
IL-8
LITAF
TL1A
IL-17
IL-17F
Garlic effects in vitro
Kim DK Lillehoj HS Lee SH Lillehoj EP Bravo D 2013 Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites Br J Nutr 109(1)76-88
a
b
a
460
480
500
520
540
560
580
600
Non-infected Control Garlicon 40
Control E acervulina infected
Body
wei
ght
gai
n (
g)
BW gain
a
b
00
05
10
15
20
25
30
Control Garlicon 40
Oocy
sts
(X10
8 )
Oocysts
b
a
0
02
04
06
08
1
Control Garlicon 40
Ab r
esponse
to p
rofilin
(O
D
450n
m)
Ab-Profilin
In vivo dietary effects of Garlic
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
Signs of poor gut health
Dibner J 2010 Int Coccidiosis Conf 10 Guangdong China
AntibioticsDiet
DrugsDiseaseStress
Furness JB 2013 Nature Reviews GastroenterologyHepatology
Bischoff BMC Medicine 2011 924
Why do we want healthy gut
Structural Intestinal Integrity-Effective Digestion and
Absorption of Food
Balanced and Stable Intestinal Microbiota
Balanced Immune Response-Absence of GI Illness
Dysbiosis and subclinical enteritis
Inflammation and acute phase immune response
Oxidative and osmotic dysfunction
Gut barrier dysfunction
Impaired nutrient synthesis (vitamins minerals SCFA)impaired energy metabolism
Low-level effect of antibiotic growth promoters on body weight gains in broilers
(Oh ST and Lillehoj HS 2017)
Mechanisms of Antibiotic Growth Promoters (AGP)
1 Anti-microbial2 Reduce subclinical infections3 Reduce microbial use of nutrients4 Reduce growth-depressing microbial metabolites5 Enhance uptake of nutrients due to histologically thinner gut
in antibiotic-treated animals6 Reduce pro-inflammatory cytokineschemokines7 In germ-free mice antibiotics increase in adiposity8 In human newborns antibiotics is associated with obesity
AGP
Competitive exclusionEnteric pathogen
Mucosal protectionInnate and adaptive immunity
Energy efficiency
Maintenance
Beneficial effects of antibiotic alternatives
Affect GI mucosa
Stimulates enzyme secretion
Improve microbial flora
Nutrient digestion
GrowthReproduction
Report of the meeting of the OIE AD HOC Group on prioritization of diseases for which vaccines could reduce antimicrobial use in animals Paris April 21-23 2015
Bacitracin GP NE CO
Virginiamycin GP NE
Coccidiosis and Necrotic Enteritis
Lillehoj HS 2015 Avian Coccidiosis as a prototype intestinal diseases In Intestinal Health Key to maximize growth performance in livestock edited by Theo Niewold Wagenigen Academic The Netherlands Pp 71-116
Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology 45313-316
Antibiotic alternatives-Mechanisms
Gadde U Lillehoj H 2017 Antibiotic Alternatives- A Review Animal Health Research Reviews In press
Essential oils key in fight against antibiotic useFeb 4 2016 1227 1
Essential oils are a key solution to an alternative for antibiotic growth promoters (AGPs) this was shown by research carried out by US food giant Cargill But what do essential oils achieve that other non-medicated feed additives donrsquot
Carbohydrate = 250 gramsProtein =100 gramsFat = 60 gramPhytonutrients =15 grams
Walsh et al 2007
ncbinlmnihgovPubmed
Function of Phytochemicals
1 Anti-oxidants carotenoids polyphenols2 Stimulates innate immunity3 Enhance adaptive (memory) immunity tumeric4 Stimulate enzymes Indole from cabbage5 Anti-bacterial allicin from garlic6 Promote beneficial bacterial growth7 Hormonal activity isoflavones from soy8 Physically block pathogen binding Proanthocyanidins9 Serve as signal transduction agents 10 Epigenetic regulation (Isoflavone tumeric)
Phytonutrientsphytochemicals Broad name for a wide variety of compounds produced by plants found in fruits vegetables beans grains and other plants
Furness 2016
Phytochemicals act on receptors on entero-endocrine cells to release hormonal messengers
Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
Son T Camandola S and Mattson M 2008 Hormetic dietary phytochemicals Neuromolecular Med 2008 10236-246
Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
Li Lillehoj et al 2010 Avian Pathology 39255 Li Lillehoj et al 2010 Avian Pathology 39247 Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology In press
Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
19
Kim DK Lillehoj HS 2014 Transcriptional profiles of host-pathogen responses to necrotic enteritis and differential regulation of immune genes in two inbreed chicken lines showing disparate disease susceptibility PLoS ONE 9(12)e114960
Avian Coccidiosis
Coccidiosis are ubiquitous they are present wherever chickens arereared (traditional industrial label or organicbio farms) Nine speciesof Eimeria have been described in chicken
Balance of Th17 and Treg cells in Coccidiosis
Th17 and Treg cells have opposite actions on intestinal immunity
Treg cells suppress a variety of physiological and
pathological immune responses in the intestine
Th17 cells play a key role in intestinal inflammation
through induction of pro-inflammatory cytokines
Dendritic cells (APC) present the antigen to the T cells
Naiumlve CD4+ T cells differentiate into either Th17 or Treg
once in contact with dendritic cells
In gut immune systemhellip
IL-17 as a potential therapeutic target of coccidiosisIL-17
bull is pro-inflammatory cytokine produced by Th17 cells
bull induces various pro-inflammatory cytokines and
mediates inflammatory response
Administration of IL-17A neutralizing antibody induce
- Enhanced weight gain
- Reduced oocyst shedding
- Increased heterophil infiltration
- Reduction of cecal lesion
- Inhibition of E tenella schizont and merozoite development
Del Cacho et al 2014 Zhang et al 2013
Kim WH Jeong J Park AR Yim D Kim S Chang HH Yang SH Kim DH Lillehoj HS Min W 2014 Downregulation of chicken interleukin-17 receptor A during Eimeria infection Infect Immun 82(9)3845-54
Flow diagram for screening immunoactive phytochemicals
Disease challenge
Macrophage activation
Lymphocyte stimulation
Cytokine Tumor cytotoxicity Direct killing of pathogens
Select synergistic plants
Nutrigenomics
In vitro screening
In vivo feeding trial
Randomized Performance analysis in commercial broilers
In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
5 ppmcarvacrol
3 ppmcinnamaldehyde
2 ppmCapsicum oleor
23
246
625198
3126
48
156
31
Primary infectionE Maxima
Secondary infectionE Maxima
Up regulated Down regulated
Kim DK Lillehoj HS Lee S H Jang S and Bravo D 2010 High-Throughput Gene Expression Analysis of Intraepithelial Lymphocytes Following dietary Carvacrol Cinnamaldehyde or Capsicum Oleoresin Poultry Science 8968-81Kim DK Lillehoj HS Min WG Kim CH Hong YH and Lillehoj EP 2011 PlosOne V6e27712
NUTRIGENOMICS to identify 3 phytonutrient combination that reduced negative effects of avian coccidiosis
From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
Phytochemical doses that we used were not cytotoxic to pathogens
Dietary effects of phytonutrients on coccidiosis
Lee S H Kim Duk Kyung Bravo D Lillehoj HS 2010 Journal Poultry Science 4789-95
Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokinetranscripts and mitigated gut damage due to necrotic enteritis
Lee SH et al Lillehoj HS Bravo DM 2013 Dietary supplementation of young broiler chickens with Capsicum and turmeric oleoresins increases resistance to necrotic enteritis Br J Nutr110(5)840-7
IL-8
LITAF
TL1A
IL-17
IL-17F
Garlic effects in vitro
Kim DK Lillehoj HS Lee SH Lillehoj EP Bravo D 2013 Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites Br J Nutr 109(1)76-88
a
b
a
460
480
500
520
540
560
580
600
Non-infected Control Garlicon 40
Control E acervulina infected
Body
wei
ght
gai
n (
g)
BW gain
a
b
00
05
10
15
20
25
30
Control Garlicon 40
Oocy
sts
(X10
8 )
Oocysts
b
a
0
02
04
06
08
1
Control Garlicon 40
Ab r
esponse
to p
rofilin
(O
D
450n
m)
Ab-Profilin
In vivo dietary effects of Garlic
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
AntibioticsDiet
DrugsDiseaseStress
Furness JB 2013 Nature Reviews GastroenterologyHepatology
Bischoff BMC Medicine 2011 924
Why do we want healthy gut
Structural Intestinal Integrity-Effective Digestion and
Absorption of Food
Balanced and Stable Intestinal Microbiota
Balanced Immune Response-Absence of GI Illness
Dysbiosis and subclinical enteritis
Inflammation and acute phase immune response
Oxidative and osmotic dysfunction
Gut barrier dysfunction
Impaired nutrient synthesis (vitamins minerals SCFA)impaired energy metabolism
Low-level effect of antibiotic growth promoters on body weight gains in broilers
(Oh ST and Lillehoj HS 2017)
Mechanisms of Antibiotic Growth Promoters (AGP)
1 Anti-microbial2 Reduce subclinical infections3 Reduce microbial use of nutrients4 Reduce growth-depressing microbial metabolites5 Enhance uptake of nutrients due to histologically thinner gut
in antibiotic-treated animals6 Reduce pro-inflammatory cytokineschemokines7 In germ-free mice antibiotics increase in adiposity8 In human newborns antibiotics is associated with obesity
AGP
Competitive exclusionEnteric pathogen
Mucosal protectionInnate and adaptive immunity
Energy efficiency
Maintenance
Beneficial effects of antibiotic alternatives
Affect GI mucosa
Stimulates enzyme secretion
Improve microbial flora
Nutrient digestion
GrowthReproduction
Report of the meeting of the OIE AD HOC Group on prioritization of diseases for which vaccines could reduce antimicrobial use in animals Paris April 21-23 2015
Bacitracin GP NE CO
Virginiamycin GP NE
Coccidiosis and Necrotic Enteritis
Lillehoj HS 2015 Avian Coccidiosis as a prototype intestinal diseases In Intestinal Health Key to maximize growth performance in livestock edited by Theo Niewold Wagenigen Academic The Netherlands Pp 71-116
Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology 45313-316
Antibiotic alternatives-Mechanisms
Gadde U Lillehoj H 2017 Antibiotic Alternatives- A Review Animal Health Research Reviews In press
Essential oils key in fight against antibiotic useFeb 4 2016 1227 1
Essential oils are a key solution to an alternative for antibiotic growth promoters (AGPs) this was shown by research carried out by US food giant Cargill But what do essential oils achieve that other non-medicated feed additives donrsquot
Carbohydrate = 250 gramsProtein =100 gramsFat = 60 gramPhytonutrients =15 grams
Walsh et al 2007
ncbinlmnihgovPubmed
Function of Phytochemicals
1 Anti-oxidants carotenoids polyphenols2 Stimulates innate immunity3 Enhance adaptive (memory) immunity tumeric4 Stimulate enzymes Indole from cabbage5 Anti-bacterial allicin from garlic6 Promote beneficial bacterial growth7 Hormonal activity isoflavones from soy8 Physically block pathogen binding Proanthocyanidins9 Serve as signal transduction agents 10 Epigenetic regulation (Isoflavone tumeric)
Phytonutrientsphytochemicals Broad name for a wide variety of compounds produced by plants found in fruits vegetables beans grains and other plants
Furness 2016
Phytochemicals act on receptors on entero-endocrine cells to release hormonal messengers
Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
Son T Camandola S and Mattson M 2008 Hormetic dietary phytochemicals Neuromolecular Med 2008 10236-246
Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
Li Lillehoj et al 2010 Avian Pathology 39255 Li Lillehoj et al 2010 Avian Pathology 39247 Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology In press
Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
19
Kim DK Lillehoj HS 2014 Transcriptional profiles of host-pathogen responses to necrotic enteritis and differential regulation of immune genes in two inbreed chicken lines showing disparate disease susceptibility PLoS ONE 9(12)e114960
Avian Coccidiosis
Coccidiosis are ubiquitous they are present wherever chickens arereared (traditional industrial label or organicbio farms) Nine speciesof Eimeria have been described in chicken
Balance of Th17 and Treg cells in Coccidiosis
Th17 and Treg cells have opposite actions on intestinal immunity
Treg cells suppress a variety of physiological and
pathological immune responses in the intestine
Th17 cells play a key role in intestinal inflammation
through induction of pro-inflammatory cytokines
Dendritic cells (APC) present the antigen to the T cells
Naiumlve CD4+ T cells differentiate into either Th17 or Treg
once in contact with dendritic cells
In gut immune systemhellip
IL-17 as a potential therapeutic target of coccidiosisIL-17
bull is pro-inflammatory cytokine produced by Th17 cells
bull induces various pro-inflammatory cytokines and
mediates inflammatory response
Administration of IL-17A neutralizing antibody induce
- Enhanced weight gain
- Reduced oocyst shedding
- Increased heterophil infiltration
- Reduction of cecal lesion
- Inhibition of E tenella schizont and merozoite development
Del Cacho et al 2014 Zhang et al 2013
Kim WH Jeong J Park AR Yim D Kim S Chang HH Yang SH Kim DH Lillehoj HS Min W 2014 Downregulation of chicken interleukin-17 receptor A during Eimeria infection Infect Immun 82(9)3845-54
Flow diagram for screening immunoactive phytochemicals
Disease challenge
Macrophage activation
Lymphocyte stimulation
Cytokine Tumor cytotoxicity Direct killing of pathogens
Select synergistic plants
Nutrigenomics
In vitro screening
In vivo feeding trial
Randomized Performance analysis in commercial broilers
In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
5 ppmcarvacrol
3 ppmcinnamaldehyde
2 ppmCapsicum oleor
23
246
625198
3126
48
156
31
Primary infectionE Maxima
Secondary infectionE Maxima
Up regulated Down regulated
Kim DK Lillehoj HS Lee S H Jang S and Bravo D 2010 High-Throughput Gene Expression Analysis of Intraepithelial Lymphocytes Following dietary Carvacrol Cinnamaldehyde or Capsicum Oleoresin Poultry Science 8968-81Kim DK Lillehoj HS Min WG Kim CH Hong YH and Lillehoj EP 2011 PlosOne V6e27712
NUTRIGENOMICS to identify 3 phytonutrient combination that reduced negative effects of avian coccidiosis
From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
Phytochemical doses that we used were not cytotoxic to pathogens
Dietary effects of phytonutrients on coccidiosis
Lee S H Kim Duk Kyung Bravo D Lillehoj HS 2010 Journal Poultry Science 4789-95
Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokinetranscripts and mitigated gut damage due to necrotic enteritis
Lee SH et al Lillehoj HS Bravo DM 2013 Dietary supplementation of young broiler chickens with Capsicum and turmeric oleoresins increases resistance to necrotic enteritis Br J Nutr110(5)840-7
IL-8
LITAF
TL1A
IL-17
IL-17F
Garlic effects in vitro
Kim DK Lillehoj HS Lee SH Lillehoj EP Bravo D 2013 Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites Br J Nutr 109(1)76-88
a
b
a
460
480
500
520
540
560
580
600
Non-infected Control Garlicon 40
Control E acervulina infected
Body
wei
ght
gai
n (
g)
BW gain
a
b
00
05
10
15
20
25
30
Control Garlicon 40
Oocy
sts
(X10
8 )
Oocysts
b
a
0
02
04
06
08
1
Control Garlicon 40
Ab r
esponse
to p
rofilin
(O
D
450n
m)
Ab-Profilin
In vivo dietary effects of Garlic
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
Bischoff BMC Medicine 2011 924
Why do we want healthy gut
Structural Intestinal Integrity-Effective Digestion and
Absorption of Food
Balanced and Stable Intestinal Microbiota
Balanced Immune Response-Absence of GI Illness
Dysbiosis and subclinical enteritis
Inflammation and acute phase immune response
Oxidative and osmotic dysfunction
Gut barrier dysfunction
Impaired nutrient synthesis (vitamins minerals SCFA)impaired energy metabolism
Low-level effect of antibiotic growth promoters on body weight gains in broilers
(Oh ST and Lillehoj HS 2017)
Mechanisms of Antibiotic Growth Promoters (AGP)
1 Anti-microbial2 Reduce subclinical infections3 Reduce microbial use of nutrients4 Reduce growth-depressing microbial metabolites5 Enhance uptake of nutrients due to histologically thinner gut
in antibiotic-treated animals6 Reduce pro-inflammatory cytokineschemokines7 In germ-free mice antibiotics increase in adiposity8 In human newborns antibiotics is associated with obesity
AGP
Competitive exclusionEnteric pathogen
Mucosal protectionInnate and adaptive immunity
Energy efficiency
Maintenance
Beneficial effects of antibiotic alternatives
Affect GI mucosa
Stimulates enzyme secretion
Improve microbial flora
Nutrient digestion
GrowthReproduction
Report of the meeting of the OIE AD HOC Group on prioritization of diseases for which vaccines could reduce antimicrobial use in animals Paris April 21-23 2015
Bacitracin GP NE CO
Virginiamycin GP NE
Coccidiosis and Necrotic Enteritis
Lillehoj HS 2015 Avian Coccidiosis as a prototype intestinal diseases In Intestinal Health Key to maximize growth performance in livestock edited by Theo Niewold Wagenigen Academic The Netherlands Pp 71-116
Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology 45313-316
Antibiotic alternatives-Mechanisms
Gadde U Lillehoj H 2017 Antibiotic Alternatives- A Review Animal Health Research Reviews In press
Essential oils key in fight against antibiotic useFeb 4 2016 1227 1
Essential oils are a key solution to an alternative for antibiotic growth promoters (AGPs) this was shown by research carried out by US food giant Cargill But what do essential oils achieve that other non-medicated feed additives donrsquot
Carbohydrate = 250 gramsProtein =100 gramsFat = 60 gramPhytonutrients =15 grams
Walsh et al 2007
ncbinlmnihgovPubmed
Function of Phytochemicals
1 Anti-oxidants carotenoids polyphenols2 Stimulates innate immunity3 Enhance adaptive (memory) immunity tumeric4 Stimulate enzymes Indole from cabbage5 Anti-bacterial allicin from garlic6 Promote beneficial bacterial growth7 Hormonal activity isoflavones from soy8 Physically block pathogen binding Proanthocyanidins9 Serve as signal transduction agents 10 Epigenetic regulation (Isoflavone tumeric)
Phytonutrientsphytochemicals Broad name for a wide variety of compounds produced by plants found in fruits vegetables beans grains and other plants
Furness 2016
Phytochemicals act on receptors on entero-endocrine cells to release hormonal messengers
Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
Son T Camandola S and Mattson M 2008 Hormetic dietary phytochemicals Neuromolecular Med 2008 10236-246
Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
Li Lillehoj et al 2010 Avian Pathology 39255 Li Lillehoj et al 2010 Avian Pathology 39247 Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology In press
Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
19
Kim DK Lillehoj HS 2014 Transcriptional profiles of host-pathogen responses to necrotic enteritis and differential regulation of immune genes in two inbreed chicken lines showing disparate disease susceptibility PLoS ONE 9(12)e114960
Avian Coccidiosis
Coccidiosis are ubiquitous they are present wherever chickens arereared (traditional industrial label or organicbio farms) Nine speciesof Eimeria have been described in chicken
Balance of Th17 and Treg cells in Coccidiosis
Th17 and Treg cells have opposite actions on intestinal immunity
Treg cells suppress a variety of physiological and
pathological immune responses in the intestine
Th17 cells play a key role in intestinal inflammation
through induction of pro-inflammatory cytokines
Dendritic cells (APC) present the antigen to the T cells
Naiumlve CD4+ T cells differentiate into either Th17 or Treg
once in contact with dendritic cells
In gut immune systemhellip
IL-17 as a potential therapeutic target of coccidiosisIL-17
bull is pro-inflammatory cytokine produced by Th17 cells
bull induces various pro-inflammatory cytokines and
mediates inflammatory response
Administration of IL-17A neutralizing antibody induce
- Enhanced weight gain
- Reduced oocyst shedding
- Increased heterophil infiltration
- Reduction of cecal lesion
- Inhibition of E tenella schizont and merozoite development
Del Cacho et al 2014 Zhang et al 2013
Kim WH Jeong J Park AR Yim D Kim S Chang HH Yang SH Kim DH Lillehoj HS Min W 2014 Downregulation of chicken interleukin-17 receptor A during Eimeria infection Infect Immun 82(9)3845-54
Flow diagram for screening immunoactive phytochemicals
Disease challenge
Macrophage activation
Lymphocyte stimulation
Cytokine Tumor cytotoxicity Direct killing of pathogens
Select synergistic plants
Nutrigenomics
In vitro screening
In vivo feeding trial
Randomized Performance analysis in commercial broilers
In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
5 ppmcarvacrol
3 ppmcinnamaldehyde
2 ppmCapsicum oleor
23
246
625198
3126
48
156
31
Primary infectionE Maxima
Secondary infectionE Maxima
Up regulated Down regulated
Kim DK Lillehoj HS Lee S H Jang S and Bravo D 2010 High-Throughput Gene Expression Analysis of Intraepithelial Lymphocytes Following dietary Carvacrol Cinnamaldehyde or Capsicum Oleoresin Poultry Science 8968-81Kim DK Lillehoj HS Min WG Kim CH Hong YH and Lillehoj EP 2011 PlosOne V6e27712
NUTRIGENOMICS to identify 3 phytonutrient combination that reduced negative effects of avian coccidiosis
From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
Phytochemical doses that we used were not cytotoxic to pathogens
Dietary effects of phytonutrients on coccidiosis
Lee S H Kim Duk Kyung Bravo D Lillehoj HS 2010 Journal Poultry Science 4789-95
Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokinetranscripts and mitigated gut damage due to necrotic enteritis
Lee SH et al Lillehoj HS Bravo DM 2013 Dietary supplementation of young broiler chickens with Capsicum and turmeric oleoresins increases resistance to necrotic enteritis Br J Nutr110(5)840-7
IL-8
LITAF
TL1A
IL-17
IL-17F
Garlic effects in vitro
Kim DK Lillehoj HS Lee SH Lillehoj EP Bravo D 2013 Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites Br J Nutr 109(1)76-88
a
b
a
460
480
500
520
540
560
580
600
Non-infected Control Garlicon 40
Control E acervulina infected
Body
wei
ght
gai
n (
g)
BW gain
a
b
00
05
10
15
20
25
30
Control Garlicon 40
Oocy
sts
(X10
8 )
Oocysts
b
a
0
02
04
06
08
1
Control Garlicon 40
Ab r
esponse
to p
rofilin
(O
D
450n
m)
Ab-Profilin
In vivo dietary effects of Garlic
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
Dysbiosis and subclinical enteritis
Inflammation and acute phase immune response
Oxidative and osmotic dysfunction
Gut barrier dysfunction
Impaired nutrient synthesis (vitamins minerals SCFA)impaired energy metabolism
Low-level effect of antibiotic growth promoters on body weight gains in broilers
(Oh ST and Lillehoj HS 2017)
Mechanisms of Antibiotic Growth Promoters (AGP)
1 Anti-microbial2 Reduce subclinical infections3 Reduce microbial use of nutrients4 Reduce growth-depressing microbial metabolites5 Enhance uptake of nutrients due to histologically thinner gut
in antibiotic-treated animals6 Reduce pro-inflammatory cytokineschemokines7 In germ-free mice antibiotics increase in adiposity8 In human newborns antibiotics is associated with obesity
AGP
Competitive exclusionEnteric pathogen
Mucosal protectionInnate and adaptive immunity
Energy efficiency
Maintenance
Beneficial effects of antibiotic alternatives
Affect GI mucosa
Stimulates enzyme secretion
Improve microbial flora
Nutrient digestion
GrowthReproduction
Report of the meeting of the OIE AD HOC Group on prioritization of diseases for which vaccines could reduce antimicrobial use in animals Paris April 21-23 2015
Bacitracin GP NE CO
Virginiamycin GP NE
Coccidiosis and Necrotic Enteritis
Lillehoj HS 2015 Avian Coccidiosis as a prototype intestinal diseases In Intestinal Health Key to maximize growth performance in livestock edited by Theo Niewold Wagenigen Academic The Netherlands Pp 71-116
Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology 45313-316
Antibiotic alternatives-Mechanisms
Gadde U Lillehoj H 2017 Antibiotic Alternatives- A Review Animal Health Research Reviews In press
Essential oils key in fight against antibiotic useFeb 4 2016 1227 1
Essential oils are a key solution to an alternative for antibiotic growth promoters (AGPs) this was shown by research carried out by US food giant Cargill But what do essential oils achieve that other non-medicated feed additives donrsquot
Carbohydrate = 250 gramsProtein =100 gramsFat = 60 gramPhytonutrients =15 grams
Walsh et al 2007
ncbinlmnihgovPubmed
Function of Phytochemicals
1 Anti-oxidants carotenoids polyphenols2 Stimulates innate immunity3 Enhance adaptive (memory) immunity tumeric4 Stimulate enzymes Indole from cabbage5 Anti-bacterial allicin from garlic6 Promote beneficial bacterial growth7 Hormonal activity isoflavones from soy8 Physically block pathogen binding Proanthocyanidins9 Serve as signal transduction agents 10 Epigenetic regulation (Isoflavone tumeric)
Phytonutrientsphytochemicals Broad name for a wide variety of compounds produced by plants found in fruits vegetables beans grains and other plants
Furness 2016
Phytochemicals act on receptors on entero-endocrine cells to release hormonal messengers
Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
Son T Camandola S and Mattson M 2008 Hormetic dietary phytochemicals Neuromolecular Med 2008 10236-246
Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
Li Lillehoj et al 2010 Avian Pathology 39255 Li Lillehoj et al 2010 Avian Pathology 39247 Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology In press
Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
19
Kim DK Lillehoj HS 2014 Transcriptional profiles of host-pathogen responses to necrotic enteritis and differential regulation of immune genes in two inbreed chicken lines showing disparate disease susceptibility PLoS ONE 9(12)e114960
Avian Coccidiosis
Coccidiosis are ubiquitous they are present wherever chickens arereared (traditional industrial label or organicbio farms) Nine speciesof Eimeria have been described in chicken
Balance of Th17 and Treg cells in Coccidiosis
Th17 and Treg cells have opposite actions on intestinal immunity
Treg cells suppress a variety of physiological and
pathological immune responses in the intestine
Th17 cells play a key role in intestinal inflammation
through induction of pro-inflammatory cytokines
Dendritic cells (APC) present the antigen to the T cells
Naiumlve CD4+ T cells differentiate into either Th17 or Treg
once in contact with dendritic cells
In gut immune systemhellip
IL-17 as a potential therapeutic target of coccidiosisIL-17
bull is pro-inflammatory cytokine produced by Th17 cells
bull induces various pro-inflammatory cytokines and
mediates inflammatory response
Administration of IL-17A neutralizing antibody induce
- Enhanced weight gain
- Reduced oocyst shedding
- Increased heterophil infiltration
- Reduction of cecal lesion
- Inhibition of E tenella schizont and merozoite development
Del Cacho et al 2014 Zhang et al 2013
Kim WH Jeong J Park AR Yim D Kim S Chang HH Yang SH Kim DH Lillehoj HS Min W 2014 Downregulation of chicken interleukin-17 receptor A during Eimeria infection Infect Immun 82(9)3845-54
Flow diagram for screening immunoactive phytochemicals
Disease challenge
Macrophage activation
Lymphocyte stimulation
Cytokine Tumor cytotoxicity Direct killing of pathogens
Select synergistic plants
Nutrigenomics
In vitro screening
In vivo feeding trial
Randomized Performance analysis in commercial broilers
In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
5 ppmcarvacrol
3 ppmcinnamaldehyde
2 ppmCapsicum oleor
23
246
625198
3126
48
156
31
Primary infectionE Maxima
Secondary infectionE Maxima
Up regulated Down regulated
Kim DK Lillehoj HS Lee S H Jang S and Bravo D 2010 High-Throughput Gene Expression Analysis of Intraepithelial Lymphocytes Following dietary Carvacrol Cinnamaldehyde or Capsicum Oleoresin Poultry Science 8968-81Kim DK Lillehoj HS Min WG Kim CH Hong YH and Lillehoj EP 2011 PlosOne V6e27712
NUTRIGENOMICS to identify 3 phytonutrient combination that reduced negative effects of avian coccidiosis
From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
Phytochemical doses that we used were not cytotoxic to pathogens
Dietary effects of phytonutrients on coccidiosis
Lee S H Kim Duk Kyung Bravo D Lillehoj HS 2010 Journal Poultry Science 4789-95
Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokinetranscripts and mitigated gut damage due to necrotic enteritis
Lee SH et al Lillehoj HS Bravo DM 2013 Dietary supplementation of young broiler chickens with Capsicum and turmeric oleoresins increases resistance to necrotic enteritis Br J Nutr110(5)840-7
IL-8
LITAF
TL1A
IL-17
IL-17F
Garlic effects in vitro
Kim DK Lillehoj HS Lee SH Lillehoj EP Bravo D 2013 Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites Br J Nutr 109(1)76-88
a
b
a
460
480
500
520
540
560
580
600
Non-infected Control Garlicon 40
Control E acervulina infected
Body
wei
ght
gai
n (
g)
BW gain
a
b
00
05
10
15
20
25
30
Control Garlicon 40
Oocy
sts
(X10
8 )
Oocysts
b
a
0
02
04
06
08
1
Control Garlicon 40
Ab r
esponse
to p
rofilin
(O
D
450n
m)
Ab-Profilin
In vivo dietary effects of Garlic
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
Low-level effect of antibiotic growth promoters on body weight gains in broilers
(Oh ST and Lillehoj HS 2017)
Mechanisms of Antibiotic Growth Promoters (AGP)
1 Anti-microbial2 Reduce subclinical infections3 Reduce microbial use of nutrients4 Reduce growth-depressing microbial metabolites5 Enhance uptake of nutrients due to histologically thinner gut
in antibiotic-treated animals6 Reduce pro-inflammatory cytokineschemokines7 In germ-free mice antibiotics increase in adiposity8 In human newborns antibiotics is associated with obesity
AGP
Competitive exclusionEnteric pathogen
Mucosal protectionInnate and adaptive immunity
Energy efficiency
Maintenance
Beneficial effects of antibiotic alternatives
Affect GI mucosa
Stimulates enzyme secretion
Improve microbial flora
Nutrient digestion
GrowthReproduction
Report of the meeting of the OIE AD HOC Group on prioritization of diseases for which vaccines could reduce antimicrobial use in animals Paris April 21-23 2015
Bacitracin GP NE CO
Virginiamycin GP NE
Coccidiosis and Necrotic Enteritis
Lillehoj HS 2015 Avian Coccidiosis as a prototype intestinal diseases In Intestinal Health Key to maximize growth performance in livestock edited by Theo Niewold Wagenigen Academic The Netherlands Pp 71-116
Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology 45313-316
Antibiotic alternatives-Mechanisms
Gadde U Lillehoj H 2017 Antibiotic Alternatives- A Review Animal Health Research Reviews In press
Essential oils key in fight against antibiotic useFeb 4 2016 1227 1
Essential oils are a key solution to an alternative for antibiotic growth promoters (AGPs) this was shown by research carried out by US food giant Cargill But what do essential oils achieve that other non-medicated feed additives donrsquot
Carbohydrate = 250 gramsProtein =100 gramsFat = 60 gramPhytonutrients =15 grams
Walsh et al 2007
ncbinlmnihgovPubmed
Function of Phytochemicals
1 Anti-oxidants carotenoids polyphenols2 Stimulates innate immunity3 Enhance adaptive (memory) immunity tumeric4 Stimulate enzymes Indole from cabbage5 Anti-bacterial allicin from garlic6 Promote beneficial bacterial growth7 Hormonal activity isoflavones from soy8 Physically block pathogen binding Proanthocyanidins9 Serve as signal transduction agents 10 Epigenetic regulation (Isoflavone tumeric)
Phytonutrientsphytochemicals Broad name for a wide variety of compounds produced by plants found in fruits vegetables beans grains and other plants
Furness 2016
Phytochemicals act on receptors on entero-endocrine cells to release hormonal messengers
Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
Son T Camandola S and Mattson M 2008 Hormetic dietary phytochemicals Neuromolecular Med 2008 10236-246
Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
Li Lillehoj et al 2010 Avian Pathology 39255 Li Lillehoj et al 2010 Avian Pathology 39247 Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology In press
Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
19
Kim DK Lillehoj HS 2014 Transcriptional profiles of host-pathogen responses to necrotic enteritis and differential regulation of immune genes in two inbreed chicken lines showing disparate disease susceptibility PLoS ONE 9(12)e114960
Avian Coccidiosis
Coccidiosis are ubiquitous they are present wherever chickens arereared (traditional industrial label or organicbio farms) Nine speciesof Eimeria have been described in chicken
Balance of Th17 and Treg cells in Coccidiosis
Th17 and Treg cells have opposite actions on intestinal immunity
Treg cells suppress a variety of physiological and
pathological immune responses in the intestine
Th17 cells play a key role in intestinal inflammation
through induction of pro-inflammatory cytokines
Dendritic cells (APC) present the antigen to the T cells
Naiumlve CD4+ T cells differentiate into either Th17 or Treg
once in contact with dendritic cells
In gut immune systemhellip
IL-17 as a potential therapeutic target of coccidiosisIL-17
bull is pro-inflammatory cytokine produced by Th17 cells
bull induces various pro-inflammatory cytokines and
mediates inflammatory response
Administration of IL-17A neutralizing antibody induce
- Enhanced weight gain
- Reduced oocyst shedding
- Increased heterophil infiltration
- Reduction of cecal lesion
- Inhibition of E tenella schizont and merozoite development
Del Cacho et al 2014 Zhang et al 2013
Kim WH Jeong J Park AR Yim D Kim S Chang HH Yang SH Kim DH Lillehoj HS Min W 2014 Downregulation of chicken interleukin-17 receptor A during Eimeria infection Infect Immun 82(9)3845-54
Flow diagram for screening immunoactive phytochemicals
Disease challenge
Macrophage activation
Lymphocyte stimulation
Cytokine Tumor cytotoxicity Direct killing of pathogens
Select synergistic plants
Nutrigenomics
In vitro screening
In vivo feeding trial
Randomized Performance analysis in commercial broilers
In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
5 ppmcarvacrol
3 ppmcinnamaldehyde
2 ppmCapsicum oleor
23
246
625198
3126
48
156
31
Primary infectionE Maxima
Secondary infectionE Maxima
Up regulated Down regulated
Kim DK Lillehoj HS Lee S H Jang S and Bravo D 2010 High-Throughput Gene Expression Analysis of Intraepithelial Lymphocytes Following dietary Carvacrol Cinnamaldehyde or Capsicum Oleoresin Poultry Science 8968-81Kim DK Lillehoj HS Min WG Kim CH Hong YH and Lillehoj EP 2011 PlosOne V6e27712
NUTRIGENOMICS to identify 3 phytonutrient combination that reduced negative effects of avian coccidiosis
From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
Phytochemical doses that we used were not cytotoxic to pathogens
Dietary effects of phytonutrients on coccidiosis
Lee S H Kim Duk Kyung Bravo D Lillehoj HS 2010 Journal Poultry Science 4789-95
Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokinetranscripts and mitigated gut damage due to necrotic enteritis
Lee SH et al Lillehoj HS Bravo DM 2013 Dietary supplementation of young broiler chickens with Capsicum and turmeric oleoresins increases resistance to necrotic enteritis Br J Nutr110(5)840-7
IL-8
LITAF
TL1A
IL-17
IL-17F
Garlic effects in vitro
Kim DK Lillehoj HS Lee SH Lillehoj EP Bravo D 2013 Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites Br J Nutr 109(1)76-88
a
b
a
460
480
500
520
540
560
580
600
Non-infected Control Garlicon 40
Control E acervulina infected
Body
wei
ght
gai
n (
g)
BW gain
a
b
00
05
10
15
20
25
30
Control Garlicon 40
Oocy
sts
(X10
8 )
Oocysts
b
a
0
02
04
06
08
1
Control Garlicon 40
Ab r
esponse
to p
rofilin
(O
D
450n
m)
Ab-Profilin
In vivo dietary effects of Garlic
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
Competitive exclusionEnteric pathogen
Mucosal protectionInnate and adaptive immunity
Energy efficiency
Maintenance
Beneficial effects of antibiotic alternatives
Affect GI mucosa
Stimulates enzyme secretion
Improve microbial flora
Nutrient digestion
GrowthReproduction
Report of the meeting of the OIE AD HOC Group on prioritization of diseases for which vaccines could reduce antimicrobial use in animals Paris April 21-23 2015
Bacitracin GP NE CO
Virginiamycin GP NE
Coccidiosis and Necrotic Enteritis
Lillehoj HS 2015 Avian Coccidiosis as a prototype intestinal diseases In Intestinal Health Key to maximize growth performance in livestock edited by Theo Niewold Wagenigen Academic The Netherlands Pp 71-116
Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology 45313-316
Antibiotic alternatives-Mechanisms
Gadde U Lillehoj H 2017 Antibiotic Alternatives- A Review Animal Health Research Reviews In press
Essential oils key in fight against antibiotic useFeb 4 2016 1227 1
Essential oils are a key solution to an alternative for antibiotic growth promoters (AGPs) this was shown by research carried out by US food giant Cargill But what do essential oils achieve that other non-medicated feed additives donrsquot
Carbohydrate = 250 gramsProtein =100 gramsFat = 60 gramPhytonutrients =15 grams
Walsh et al 2007
ncbinlmnihgovPubmed
Function of Phytochemicals
1 Anti-oxidants carotenoids polyphenols2 Stimulates innate immunity3 Enhance adaptive (memory) immunity tumeric4 Stimulate enzymes Indole from cabbage5 Anti-bacterial allicin from garlic6 Promote beneficial bacterial growth7 Hormonal activity isoflavones from soy8 Physically block pathogen binding Proanthocyanidins9 Serve as signal transduction agents 10 Epigenetic regulation (Isoflavone tumeric)
Phytonutrientsphytochemicals Broad name for a wide variety of compounds produced by plants found in fruits vegetables beans grains and other plants
Furness 2016
Phytochemicals act on receptors on entero-endocrine cells to release hormonal messengers
Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
Son T Camandola S and Mattson M 2008 Hormetic dietary phytochemicals Neuromolecular Med 2008 10236-246
Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
Li Lillehoj et al 2010 Avian Pathology 39255 Li Lillehoj et al 2010 Avian Pathology 39247 Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology In press
Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
19
Kim DK Lillehoj HS 2014 Transcriptional profiles of host-pathogen responses to necrotic enteritis and differential regulation of immune genes in two inbreed chicken lines showing disparate disease susceptibility PLoS ONE 9(12)e114960
Avian Coccidiosis
Coccidiosis are ubiquitous they are present wherever chickens arereared (traditional industrial label or organicbio farms) Nine speciesof Eimeria have been described in chicken
Balance of Th17 and Treg cells in Coccidiosis
Th17 and Treg cells have opposite actions on intestinal immunity
Treg cells suppress a variety of physiological and
pathological immune responses in the intestine
Th17 cells play a key role in intestinal inflammation
through induction of pro-inflammatory cytokines
Dendritic cells (APC) present the antigen to the T cells
Naiumlve CD4+ T cells differentiate into either Th17 or Treg
once in contact with dendritic cells
In gut immune systemhellip
IL-17 as a potential therapeutic target of coccidiosisIL-17
bull is pro-inflammatory cytokine produced by Th17 cells
bull induces various pro-inflammatory cytokines and
mediates inflammatory response
Administration of IL-17A neutralizing antibody induce
- Enhanced weight gain
- Reduced oocyst shedding
- Increased heterophil infiltration
- Reduction of cecal lesion
- Inhibition of E tenella schizont and merozoite development
Del Cacho et al 2014 Zhang et al 2013
Kim WH Jeong J Park AR Yim D Kim S Chang HH Yang SH Kim DH Lillehoj HS Min W 2014 Downregulation of chicken interleukin-17 receptor A during Eimeria infection Infect Immun 82(9)3845-54
Flow diagram for screening immunoactive phytochemicals
Disease challenge
Macrophage activation
Lymphocyte stimulation
Cytokine Tumor cytotoxicity Direct killing of pathogens
Select synergistic plants
Nutrigenomics
In vitro screening
In vivo feeding trial
Randomized Performance analysis in commercial broilers
In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
5 ppmcarvacrol
3 ppmcinnamaldehyde
2 ppmCapsicum oleor
23
246
625198
3126
48
156
31
Primary infectionE Maxima
Secondary infectionE Maxima
Up regulated Down regulated
Kim DK Lillehoj HS Lee S H Jang S and Bravo D 2010 High-Throughput Gene Expression Analysis of Intraepithelial Lymphocytes Following dietary Carvacrol Cinnamaldehyde or Capsicum Oleoresin Poultry Science 8968-81Kim DK Lillehoj HS Min WG Kim CH Hong YH and Lillehoj EP 2011 PlosOne V6e27712
NUTRIGENOMICS to identify 3 phytonutrient combination that reduced negative effects of avian coccidiosis
From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
Phytochemical doses that we used were not cytotoxic to pathogens
Dietary effects of phytonutrients on coccidiosis
Lee S H Kim Duk Kyung Bravo D Lillehoj HS 2010 Journal Poultry Science 4789-95
Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokinetranscripts and mitigated gut damage due to necrotic enteritis
Lee SH et al Lillehoj HS Bravo DM 2013 Dietary supplementation of young broiler chickens with Capsicum and turmeric oleoresins increases resistance to necrotic enteritis Br J Nutr110(5)840-7
IL-8
LITAF
TL1A
IL-17
IL-17F
Garlic effects in vitro
Kim DK Lillehoj HS Lee SH Lillehoj EP Bravo D 2013 Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites Br J Nutr 109(1)76-88
a
b
a
460
480
500
520
540
560
580
600
Non-infected Control Garlicon 40
Control E acervulina infected
Body
wei
ght
gai
n (
g)
BW gain
a
b
00
05
10
15
20
25
30
Control Garlicon 40
Oocy
sts
(X10
8 )
Oocysts
b
a
0
02
04
06
08
1
Control Garlicon 40
Ab r
esponse
to p
rofilin
(O
D
450n
m)
Ab-Profilin
In vivo dietary effects of Garlic
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
Report of the meeting of the OIE AD HOC Group on prioritization of diseases for which vaccines could reduce antimicrobial use in animals Paris April 21-23 2015
Bacitracin GP NE CO
Virginiamycin GP NE
Coccidiosis and Necrotic Enteritis
Lillehoj HS 2015 Avian Coccidiosis as a prototype intestinal diseases In Intestinal Health Key to maximize growth performance in livestock edited by Theo Niewold Wagenigen Academic The Netherlands Pp 71-116
Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology 45313-316
Antibiotic alternatives-Mechanisms
Gadde U Lillehoj H 2017 Antibiotic Alternatives- A Review Animal Health Research Reviews In press
Essential oils key in fight against antibiotic useFeb 4 2016 1227 1
Essential oils are a key solution to an alternative for antibiotic growth promoters (AGPs) this was shown by research carried out by US food giant Cargill But what do essential oils achieve that other non-medicated feed additives donrsquot
Carbohydrate = 250 gramsProtein =100 gramsFat = 60 gramPhytonutrients =15 grams
Walsh et al 2007
ncbinlmnihgovPubmed
Function of Phytochemicals
1 Anti-oxidants carotenoids polyphenols2 Stimulates innate immunity3 Enhance adaptive (memory) immunity tumeric4 Stimulate enzymes Indole from cabbage5 Anti-bacterial allicin from garlic6 Promote beneficial bacterial growth7 Hormonal activity isoflavones from soy8 Physically block pathogen binding Proanthocyanidins9 Serve as signal transduction agents 10 Epigenetic regulation (Isoflavone tumeric)
Phytonutrientsphytochemicals Broad name for a wide variety of compounds produced by plants found in fruits vegetables beans grains and other plants
Furness 2016
Phytochemicals act on receptors on entero-endocrine cells to release hormonal messengers
Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
Son T Camandola S and Mattson M 2008 Hormetic dietary phytochemicals Neuromolecular Med 2008 10236-246
Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
Li Lillehoj et al 2010 Avian Pathology 39255 Li Lillehoj et al 2010 Avian Pathology 39247 Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology In press
Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
19
Kim DK Lillehoj HS 2014 Transcriptional profiles of host-pathogen responses to necrotic enteritis and differential regulation of immune genes in two inbreed chicken lines showing disparate disease susceptibility PLoS ONE 9(12)e114960
Avian Coccidiosis
Coccidiosis are ubiquitous they are present wherever chickens arereared (traditional industrial label or organicbio farms) Nine speciesof Eimeria have been described in chicken
Balance of Th17 and Treg cells in Coccidiosis
Th17 and Treg cells have opposite actions on intestinal immunity
Treg cells suppress a variety of physiological and
pathological immune responses in the intestine
Th17 cells play a key role in intestinal inflammation
through induction of pro-inflammatory cytokines
Dendritic cells (APC) present the antigen to the T cells
Naiumlve CD4+ T cells differentiate into either Th17 or Treg
once in contact with dendritic cells
In gut immune systemhellip
IL-17 as a potential therapeutic target of coccidiosisIL-17
bull is pro-inflammatory cytokine produced by Th17 cells
bull induces various pro-inflammatory cytokines and
mediates inflammatory response
Administration of IL-17A neutralizing antibody induce
- Enhanced weight gain
- Reduced oocyst shedding
- Increased heterophil infiltration
- Reduction of cecal lesion
- Inhibition of E tenella schizont and merozoite development
Del Cacho et al 2014 Zhang et al 2013
Kim WH Jeong J Park AR Yim D Kim S Chang HH Yang SH Kim DH Lillehoj HS Min W 2014 Downregulation of chicken interleukin-17 receptor A during Eimeria infection Infect Immun 82(9)3845-54
Flow diagram for screening immunoactive phytochemicals
Disease challenge
Macrophage activation
Lymphocyte stimulation
Cytokine Tumor cytotoxicity Direct killing of pathogens
Select synergistic plants
Nutrigenomics
In vitro screening
In vivo feeding trial
Randomized Performance analysis in commercial broilers
In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
5 ppmcarvacrol
3 ppmcinnamaldehyde
2 ppmCapsicum oleor
23
246
625198
3126
48
156
31
Primary infectionE Maxima
Secondary infectionE Maxima
Up regulated Down regulated
Kim DK Lillehoj HS Lee S H Jang S and Bravo D 2010 High-Throughput Gene Expression Analysis of Intraepithelial Lymphocytes Following dietary Carvacrol Cinnamaldehyde or Capsicum Oleoresin Poultry Science 8968-81Kim DK Lillehoj HS Min WG Kim CH Hong YH and Lillehoj EP 2011 PlosOne V6e27712
NUTRIGENOMICS to identify 3 phytonutrient combination that reduced negative effects of avian coccidiosis
From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
Phytochemical doses that we used were not cytotoxic to pathogens
Dietary effects of phytonutrients on coccidiosis
Lee S H Kim Duk Kyung Bravo D Lillehoj HS 2010 Journal Poultry Science 4789-95
Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokinetranscripts and mitigated gut damage due to necrotic enteritis
Lee SH et al Lillehoj HS Bravo DM 2013 Dietary supplementation of young broiler chickens with Capsicum and turmeric oleoresins increases resistance to necrotic enteritis Br J Nutr110(5)840-7
IL-8
LITAF
TL1A
IL-17
IL-17F
Garlic effects in vitro
Kim DK Lillehoj HS Lee SH Lillehoj EP Bravo D 2013 Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites Br J Nutr 109(1)76-88
a
b
a
460
480
500
520
540
560
580
600
Non-infected Control Garlicon 40
Control E acervulina infected
Body
wei
ght
gai
n (
g)
BW gain
a
b
00
05
10
15
20
25
30
Control Garlicon 40
Oocy
sts
(X10
8 )
Oocysts
b
a
0
02
04
06
08
1
Control Garlicon 40
Ab r
esponse
to p
rofilin
(O
D
450n
m)
Ab-Profilin
In vivo dietary effects of Garlic
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
Coccidiosis and Necrotic Enteritis
Lillehoj HS 2015 Avian Coccidiosis as a prototype intestinal diseases In Intestinal Health Key to maximize growth performance in livestock edited by Theo Niewold Wagenigen Academic The Netherlands Pp 71-116
Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology 45313-316
Antibiotic alternatives-Mechanisms
Gadde U Lillehoj H 2017 Antibiotic Alternatives- A Review Animal Health Research Reviews In press
Essential oils key in fight against antibiotic useFeb 4 2016 1227 1
Essential oils are a key solution to an alternative for antibiotic growth promoters (AGPs) this was shown by research carried out by US food giant Cargill But what do essential oils achieve that other non-medicated feed additives donrsquot
Carbohydrate = 250 gramsProtein =100 gramsFat = 60 gramPhytonutrients =15 grams
Walsh et al 2007
ncbinlmnihgovPubmed
Function of Phytochemicals
1 Anti-oxidants carotenoids polyphenols2 Stimulates innate immunity3 Enhance adaptive (memory) immunity tumeric4 Stimulate enzymes Indole from cabbage5 Anti-bacterial allicin from garlic6 Promote beneficial bacterial growth7 Hormonal activity isoflavones from soy8 Physically block pathogen binding Proanthocyanidins9 Serve as signal transduction agents 10 Epigenetic regulation (Isoflavone tumeric)
Phytonutrientsphytochemicals Broad name for a wide variety of compounds produced by plants found in fruits vegetables beans grains and other plants
Furness 2016
Phytochemicals act on receptors on entero-endocrine cells to release hormonal messengers
Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
Son T Camandola S and Mattson M 2008 Hormetic dietary phytochemicals Neuromolecular Med 2008 10236-246
Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
Li Lillehoj et al 2010 Avian Pathology 39255 Li Lillehoj et al 2010 Avian Pathology 39247 Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology In press
Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
19
Kim DK Lillehoj HS 2014 Transcriptional profiles of host-pathogen responses to necrotic enteritis and differential regulation of immune genes in two inbreed chicken lines showing disparate disease susceptibility PLoS ONE 9(12)e114960
Avian Coccidiosis
Coccidiosis are ubiquitous they are present wherever chickens arereared (traditional industrial label or organicbio farms) Nine speciesof Eimeria have been described in chicken
Balance of Th17 and Treg cells in Coccidiosis
Th17 and Treg cells have opposite actions on intestinal immunity
Treg cells suppress a variety of physiological and
pathological immune responses in the intestine
Th17 cells play a key role in intestinal inflammation
through induction of pro-inflammatory cytokines
Dendritic cells (APC) present the antigen to the T cells
Naiumlve CD4+ T cells differentiate into either Th17 or Treg
once in contact with dendritic cells
In gut immune systemhellip
IL-17 as a potential therapeutic target of coccidiosisIL-17
bull is pro-inflammatory cytokine produced by Th17 cells
bull induces various pro-inflammatory cytokines and
mediates inflammatory response
Administration of IL-17A neutralizing antibody induce
- Enhanced weight gain
- Reduced oocyst shedding
- Increased heterophil infiltration
- Reduction of cecal lesion
- Inhibition of E tenella schizont and merozoite development
Del Cacho et al 2014 Zhang et al 2013
Kim WH Jeong J Park AR Yim D Kim S Chang HH Yang SH Kim DH Lillehoj HS Min W 2014 Downregulation of chicken interleukin-17 receptor A during Eimeria infection Infect Immun 82(9)3845-54
Flow diagram for screening immunoactive phytochemicals
Disease challenge
Macrophage activation
Lymphocyte stimulation
Cytokine Tumor cytotoxicity Direct killing of pathogens
Select synergistic plants
Nutrigenomics
In vitro screening
In vivo feeding trial
Randomized Performance analysis in commercial broilers
In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
5 ppmcarvacrol
3 ppmcinnamaldehyde
2 ppmCapsicum oleor
23
246
625198
3126
48
156
31
Primary infectionE Maxima
Secondary infectionE Maxima
Up regulated Down regulated
Kim DK Lillehoj HS Lee S H Jang S and Bravo D 2010 High-Throughput Gene Expression Analysis of Intraepithelial Lymphocytes Following dietary Carvacrol Cinnamaldehyde or Capsicum Oleoresin Poultry Science 8968-81Kim DK Lillehoj HS Min WG Kim CH Hong YH and Lillehoj EP 2011 PlosOne V6e27712
NUTRIGENOMICS to identify 3 phytonutrient combination that reduced negative effects of avian coccidiosis
From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
Phytochemical doses that we used were not cytotoxic to pathogens
Dietary effects of phytonutrients on coccidiosis
Lee S H Kim Duk Kyung Bravo D Lillehoj HS 2010 Journal Poultry Science 4789-95
Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokinetranscripts and mitigated gut damage due to necrotic enteritis
Lee SH et al Lillehoj HS Bravo DM 2013 Dietary supplementation of young broiler chickens with Capsicum and turmeric oleoresins increases resistance to necrotic enteritis Br J Nutr110(5)840-7
IL-8
LITAF
TL1A
IL-17
IL-17F
Garlic effects in vitro
Kim DK Lillehoj HS Lee SH Lillehoj EP Bravo D 2013 Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites Br J Nutr 109(1)76-88
a
b
a
460
480
500
520
540
560
580
600
Non-infected Control Garlicon 40
Control E acervulina infected
Body
wei
ght
gai
n (
g)
BW gain
a
b
00
05
10
15
20
25
30
Control Garlicon 40
Oocy
sts
(X10
8 )
Oocysts
b
a
0
02
04
06
08
1
Control Garlicon 40
Ab r
esponse
to p
rofilin
(O
D
450n
m)
Ab-Profilin
In vivo dietary effects of Garlic
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
Antibiotic alternatives-Mechanisms
Gadde U Lillehoj H 2017 Antibiotic Alternatives- A Review Animal Health Research Reviews In press
Essential oils key in fight against antibiotic useFeb 4 2016 1227 1
Essential oils are a key solution to an alternative for antibiotic growth promoters (AGPs) this was shown by research carried out by US food giant Cargill But what do essential oils achieve that other non-medicated feed additives donrsquot
Carbohydrate = 250 gramsProtein =100 gramsFat = 60 gramPhytonutrients =15 grams
Walsh et al 2007
ncbinlmnihgovPubmed
Function of Phytochemicals
1 Anti-oxidants carotenoids polyphenols2 Stimulates innate immunity3 Enhance adaptive (memory) immunity tumeric4 Stimulate enzymes Indole from cabbage5 Anti-bacterial allicin from garlic6 Promote beneficial bacterial growth7 Hormonal activity isoflavones from soy8 Physically block pathogen binding Proanthocyanidins9 Serve as signal transduction agents 10 Epigenetic regulation (Isoflavone tumeric)
Phytonutrientsphytochemicals Broad name for a wide variety of compounds produced by plants found in fruits vegetables beans grains and other plants
Furness 2016
Phytochemicals act on receptors on entero-endocrine cells to release hormonal messengers
Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
Son T Camandola S and Mattson M 2008 Hormetic dietary phytochemicals Neuromolecular Med 2008 10236-246
Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
Li Lillehoj et al 2010 Avian Pathology 39255 Li Lillehoj et al 2010 Avian Pathology 39247 Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology In press
Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
19
Kim DK Lillehoj HS 2014 Transcriptional profiles of host-pathogen responses to necrotic enteritis and differential regulation of immune genes in two inbreed chicken lines showing disparate disease susceptibility PLoS ONE 9(12)e114960
Avian Coccidiosis
Coccidiosis are ubiquitous they are present wherever chickens arereared (traditional industrial label or organicbio farms) Nine speciesof Eimeria have been described in chicken
Balance of Th17 and Treg cells in Coccidiosis
Th17 and Treg cells have opposite actions on intestinal immunity
Treg cells suppress a variety of physiological and
pathological immune responses in the intestine
Th17 cells play a key role in intestinal inflammation
through induction of pro-inflammatory cytokines
Dendritic cells (APC) present the antigen to the T cells
Naiumlve CD4+ T cells differentiate into either Th17 or Treg
once in contact with dendritic cells
In gut immune systemhellip
IL-17 as a potential therapeutic target of coccidiosisIL-17
bull is pro-inflammatory cytokine produced by Th17 cells
bull induces various pro-inflammatory cytokines and
mediates inflammatory response
Administration of IL-17A neutralizing antibody induce
- Enhanced weight gain
- Reduced oocyst shedding
- Increased heterophil infiltration
- Reduction of cecal lesion
- Inhibition of E tenella schizont and merozoite development
Del Cacho et al 2014 Zhang et al 2013
Kim WH Jeong J Park AR Yim D Kim S Chang HH Yang SH Kim DH Lillehoj HS Min W 2014 Downregulation of chicken interleukin-17 receptor A during Eimeria infection Infect Immun 82(9)3845-54
Flow diagram for screening immunoactive phytochemicals
Disease challenge
Macrophage activation
Lymphocyte stimulation
Cytokine Tumor cytotoxicity Direct killing of pathogens
Select synergistic plants
Nutrigenomics
In vitro screening
In vivo feeding trial
Randomized Performance analysis in commercial broilers
In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
5 ppmcarvacrol
3 ppmcinnamaldehyde
2 ppmCapsicum oleor
23
246
625198
3126
48
156
31
Primary infectionE Maxima
Secondary infectionE Maxima
Up regulated Down regulated
Kim DK Lillehoj HS Lee S H Jang S and Bravo D 2010 High-Throughput Gene Expression Analysis of Intraepithelial Lymphocytes Following dietary Carvacrol Cinnamaldehyde or Capsicum Oleoresin Poultry Science 8968-81Kim DK Lillehoj HS Min WG Kim CH Hong YH and Lillehoj EP 2011 PlosOne V6e27712
NUTRIGENOMICS to identify 3 phytonutrient combination that reduced negative effects of avian coccidiosis
From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
Phytochemical doses that we used were not cytotoxic to pathogens
Dietary effects of phytonutrients on coccidiosis
Lee S H Kim Duk Kyung Bravo D Lillehoj HS 2010 Journal Poultry Science 4789-95
Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokinetranscripts and mitigated gut damage due to necrotic enteritis
Lee SH et al Lillehoj HS Bravo DM 2013 Dietary supplementation of young broiler chickens with Capsicum and turmeric oleoresins increases resistance to necrotic enteritis Br J Nutr110(5)840-7
IL-8
LITAF
TL1A
IL-17
IL-17F
Garlic effects in vitro
Kim DK Lillehoj HS Lee SH Lillehoj EP Bravo D 2013 Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites Br J Nutr 109(1)76-88
a
b
a
460
480
500
520
540
560
580
600
Non-infected Control Garlicon 40
Control E acervulina infected
Body
wei
ght
gai
n (
g)
BW gain
a
b
00
05
10
15
20
25
30
Control Garlicon 40
Oocy
sts
(X10
8 )
Oocysts
b
a
0
02
04
06
08
1
Control Garlicon 40
Ab r
esponse
to p
rofilin
(O
D
450n
m)
Ab-Profilin
In vivo dietary effects of Garlic
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
Essential oils key in fight against antibiotic useFeb 4 2016 1227 1
Essential oils are a key solution to an alternative for antibiotic growth promoters (AGPs) this was shown by research carried out by US food giant Cargill But what do essential oils achieve that other non-medicated feed additives donrsquot
Carbohydrate = 250 gramsProtein =100 gramsFat = 60 gramPhytonutrients =15 grams
Walsh et al 2007
ncbinlmnihgovPubmed
Function of Phytochemicals
1 Anti-oxidants carotenoids polyphenols2 Stimulates innate immunity3 Enhance adaptive (memory) immunity tumeric4 Stimulate enzymes Indole from cabbage5 Anti-bacterial allicin from garlic6 Promote beneficial bacterial growth7 Hormonal activity isoflavones from soy8 Physically block pathogen binding Proanthocyanidins9 Serve as signal transduction agents 10 Epigenetic regulation (Isoflavone tumeric)
Phytonutrientsphytochemicals Broad name for a wide variety of compounds produced by plants found in fruits vegetables beans grains and other plants
Furness 2016
Phytochemicals act on receptors on entero-endocrine cells to release hormonal messengers
Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
Son T Camandola S and Mattson M 2008 Hormetic dietary phytochemicals Neuromolecular Med 2008 10236-246
Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
Li Lillehoj et al 2010 Avian Pathology 39255 Li Lillehoj et al 2010 Avian Pathology 39247 Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology In press
Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
19
Kim DK Lillehoj HS 2014 Transcriptional profiles of host-pathogen responses to necrotic enteritis and differential regulation of immune genes in two inbreed chicken lines showing disparate disease susceptibility PLoS ONE 9(12)e114960
Avian Coccidiosis
Coccidiosis are ubiquitous they are present wherever chickens arereared (traditional industrial label or organicbio farms) Nine speciesof Eimeria have been described in chicken
Balance of Th17 and Treg cells in Coccidiosis
Th17 and Treg cells have opposite actions on intestinal immunity
Treg cells suppress a variety of physiological and
pathological immune responses in the intestine
Th17 cells play a key role in intestinal inflammation
through induction of pro-inflammatory cytokines
Dendritic cells (APC) present the antigen to the T cells
Naiumlve CD4+ T cells differentiate into either Th17 or Treg
once in contact with dendritic cells
In gut immune systemhellip
IL-17 as a potential therapeutic target of coccidiosisIL-17
bull is pro-inflammatory cytokine produced by Th17 cells
bull induces various pro-inflammatory cytokines and
mediates inflammatory response
Administration of IL-17A neutralizing antibody induce
- Enhanced weight gain
- Reduced oocyst shedding
- Increased heterophil infiltration
- Reduction of cecal lesion
- Inhibition of E tenella schizont and merozoite development
Del Cacho et al 2014 Zhang et al 2013
Kim WH Jeong J Park AR Yim D Kim S Chang HH Yang SH Kim DH Lillehoj HS Min W 2014 Downregulation of chicken interleukin-17 receptor A during Eimeria infection Infect Immun 82(9)3845-54
Flow diagram for screening immunoactive phytochemicals
Disease challenge
Macrophage activation
Lymphocyte stimulation
Cytokine Tumor cytotoxicity Direct killing of pathogens
Select synergistic plants
Nutrigenomics
In vitro screening
In vivo feeding trial
Randomized Performance analysis in commercial broilers
In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
5 ppmcarvacrol
3 ppmcinnamaldehyde
2 ppmCapsicum oleor
23
246
625198
3126
48
156
31
Primary infectionE Maxima
Secondary infectionE Maxima
Up regulated Down regulated
Kim DK Lillehoj HS Lee S H Jang S and Bravo D 2010 High-Throughput Gene Expression Analysis of Intraepithelial Lymphocytes Following dietary Carvacrol Cinnamaldehyde or Capsicum Oleoresin Poultry Science 8968-81Kim DK Lillehoj HS Min WG Kim CH Hong YH and Lillehoj EP 2011 PlosOne V6e27712
NUTRIGENOMICS to identify 3 phytonutrient combination that reduced negative effects of avian coccidiosis
From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
Phytochemical doses that we used were not cytotoxic to pathogens
Dietary effects of phytonutrients on coccidiosis
Lee S H Kim Duk Kyung Bravo D Lillehoj HS 2010 Journal Poultry Science 4789-95
Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokinetranscripts and mitigated gut damage due to necrotic enteritis
Lee SH et al Lillehoj HS Bravo DM 2013 Dietary supplementation of young broiler chickens with Capsicum and turmeric oleoresins increases resistance to necrotic enteritis Br J Nutr110(5)840-7
IL-8
LITAF
TL1A
IL-17
IL-17F
Garlic effects in vitro
Kim DK Lillehoj HS Lee SH Lillehoj EP Bravo D 2013 Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites Br J Nutr 109(1)76-88
a
b
a
460
480
500
520
540
560
580
600
Non-infected Control Garlicon 40
Control E acervulina infected
Body
wei
ght
gai
n (
g)
BW gain
a
b
00
05
10
15
20
25
30
Control Garlicon 40
Oocy
sts
(X10
8 )
Oocysts
b
a
0
02
04
06
08
1
Control Garlicon 40
Ab r
esponse
to p
rofilin
(O
D
450n
m)
Ab-Profilin
In vivo dietary effects of Garlic
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
Function of Phytochemicals
1 Anti-oxidants carotenoids polyphenols2 Stimulates innate immunity3 Enhance adaptive (memory) immunity tumeric4 Stimulate enzymes Indole from cabbage5 Anti-bacterial allicin from garlic6 Promote beneficial bacterial growth7 Hormonal activity isoflavones from soy8 Physically block pathogen binding Proanthocyanidins9 Serve as signal transduction agents 10 Epigenetic regulation (Isoflavone tumeric)
Phytonutrientsphytochemicals Broad name for a wide variety of compounds produced by plants found in fruits vegetables beans grains and other plants
Furness 2016
Phytochemicals act on receptors on entero-endocrine cells to release hormonal messengers
Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
Son T Camandola S and Mattson M 2008 Hormetic dietary phytochemicals Neuromolecular Med 2008 10236-246
Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
Li Lillehoj et al 2010 Avian Pathology 39255 Li Lillehoj et al 2010 Avian Pathology 39247 Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology In press
Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
19
Kim DK Lillehoj HS 2014 Transcriptional profiles of host-pathogen responses to necrotic enteritis and differential regulation of immune genes in two inbreed chicken lines showing disparate disease susceptibility PLoS ONE 9(12)e114960
Avian Coccidiosis
Coccidiosis are ubiquitous they are present wherever chickens arereared (traditional industrial label or organicbio farms) Nine speciesof Eimeria have been described in chicken
Balance of Th17 and Treg cells in Coccidiosis
Th17 and Treg cells have opposite actions on intestinal immunity
Treg cells suppress a variety of physiological and
pathological immune responses in the intestine
Th17 cells play a key role in intestinal inflammation
through induction of pro-inflammatory cytokines
Dendritic cells (APC) present the antigen to the T cells
Naiumlve CD4+ T cells differentiate into either Th17 or Treg
once in contact with dendritic cells
In gut immune systemhellip
IL-17 as a potential therapeutic target of coccidiosisIL-17
bull is pro-inflammatory cytokine produced by Th17 cells
bull induces various pro-inflammatory cytokines and
mediates inflammatory response
Administration of IL-17A neutralizing antibody induce
- Enhanced weight gain
- Reduced oocyst shedding
- Increased heterophil infiltration
- Reduction of cecal lesion
- Inhibition of E tenella schizont and merozoite development
Del Cacho et al 2014 Zhang et al 2013
Kim WH Jeong J Park AR Yim D Kim S Chang HH Yang SH Kim DH Lillehoj HS Min W 2014 Downregulation of chicken interleukin-17 receptor A during Eimeria infection Infect Immun 82(9)3845-54
Flow diagram for screening immunoactive phytochemicals
Disease challenge
Macrophage activation
Lymphocyte stimulation
Cytokine Tumor cytotoxicity Direct killing of pathogens
Select synergistic plants
Nutrigenomics
In vitro screening
In vivo feeding trial
Randomized Performance analysis in commercial broilers
In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
5 ppmcarvacrol
3 ppmcinnamaldehyde
2 ppmCapsicum oleor
23
246
625198
3126
48
156
31
Primary infectionE Maxima
Secondary infectionE Maxima
Up regulated Down regulated
Kim DK Lillehoj HS Lee S H Jang S and Bravo D 2010 High-Throughput Gene Expression Analysis of Intraepithelial Lymphocytes Following dietary Carvacrol Cinnamaldehyde or Capsicum Oleoresin Poultry Science 8968-81Kim DK Lillehoj HS Min WG Kim CH Hong YH and Lillehoj EP 2011 PlosOne V6e27712
NUTRIGENOMICS to identify 3 phytonutrient combination that reduced negative effects of avian coccidiosis
From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
Phytochemical doses that we used were not cytotoxic to pathogens
Dietary effects of phytonutrients on coccidiosis
Lee S H Kim Duk Kyung Bravo D Lillehoj HS 2010 Journal Poultry Science 4789-95
Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokinetranscripts and mitigated gut damage due to necrotic enteritis
Lee SH et al Lillehoj HS Bravo DM 2013 Dietary supplementation of young broiler chickens with Capsicum and turmeric oleoresins increases resistance to necrotic enteritis Br J Nutr110(5)840-7
IL-8
LITAF
TL1A
IL-17
IL-17F
Garlic effects in vitro
Kim DK Lillehoj HS Lee SH Lillehoj EP Bravo D 2013 Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites Br J Nutr 109(1)76-88
a
b
a
460
480
500
520
540
560
580
600
Non-infected Control Garlicon 40
Control E acervulina infected
Body
wei
ght
gai
n (
g)
BW gain
a
b
00
05
10
15
20
25
30
Control Garlicon 40
Oocy
sts
(X10
8 )
Oocysts
b
a
0
02
04
06
08
1
Control Garlicon 40
Ab r
esponse
to p
rofilin
(O
D
450n
m)
Ab-Profilin
In vivo dietary effects of Garlic
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
Furness 2016
Phytochemicals act on receptors on entero-endocrine cells to release hormonal messengers
Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
Son T Camandola S and Mattson M 2008 Hormetic dietary phytochemicals Neuromolecular Med 2008 10236-246
Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
Li Lillehoj et al 2010 Avian Pathology 39255 Li Lillehoj et al 2010 Avian Pathology 39247 Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology In press
Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
19
Kim DK Lillehoj HS 2014 Transcriptional profiles of host-pathogen responses to necrotic enteritis and differential regulation of immune genes in two inbreed chicken lines showing disparate disease susceptibility PLoS ONE 9(12)e114960
Avian Coccidiosis
Coccidiosis are ubiquitous they are present wherever chickens arereared (traditional industrial label or organicbio farms) Nine speciesof Eimeria have been described in chicken
Balance of Th17 and Treg cells in Coccidiosis
Th17 and Treg cells have opposite actions on intestinal immunity
Treg cells suppress a variety of physiological and
pathological immune responses in the intestine
Th17 cells play a key role in intestinal inflammation
through induction of pro-inflammatory cytokines
Dendritic cells (APC) present the antigen to the T cells
Naiumlve CD4+ T cells differentiate into either Th17 or Treg
once in contact with dendritic cells
In gut immune systemhellip
IL-17 as a potential therapeutic target of coccidiosisIL-17
bull is pro-inflammatory cytokine produced by Th17 cells
bull induces various pro-inflammatory cytokines and
mediates inflammatory response
Administration of IL-17A neutralizing antibody induce
- Enhanced weight gain
- Reduced oocyst shedding
- Increased heterophil infiltration
- Reduction of cecal lesion
- Inhibition of E tenella schizont and merozoite development
Del Cacho et al 2014 Zhang et al 2013
Kim WH Jeong J Park AR Yim D Kim S Chang HH Yang SH Kim DH Lillehoj HS Min W 2014 Downregulation of chicken interleukin-17 receptor A during Eimeria infection Infect Immun 82(9)3845-54
Flow diagram for screening immunoactive phytochemicals
Disease challenge
Macrophage activation
Lymphocyte stimulation
Cytokine Tumor cytotoxicity Direct killing of pathogens
Select synergistic plants
Nutrigenomics
In vitro screening
In vivo feeding trial
Randomized Performance analysis in commercial broilers
In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
5 ppmcarvacrol
3 ppmcinnamaldehyde
2 ppmCapsicum oleor
23
246
625198
3126
48
156
31
Primary infectionE Maxima
Secondary infectionE Maxima
Up regulated Down regulated
Kim DK Lillehoj HS Lee S H Jang S and Bravo D 2010 High-Throughput Gene Expression Analysis of Intraepithelial Lymphocytes Following dietary Carvacrol Cinnamaldehyde or Capsicum Oleoresin Poultry Science 8968-81Kim DK Lillehoj HS Min WG Kim CH Hong YH and Lillehoj EP 2011 PlosOne V6e27712
NUTRIGENOMICS to identify 3 phytonutrient combination that reduced negative effects of avian coccidiosis
From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
Phytochemical doses that we used were not cytotoxic to pathogens
Dietary effects of phytonutrients on coccidiosis
Lee S H Kim Duk Kyung Bravo D Lillehoj HS 2010 Journal Poultry Science 4789-95
Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokinetranscripts and mitigated gut damage due to necrotic enteritis
Lee SH et al Lillehoj HS Bravo DM 2013 Dietary supplementation of young broiler chickens with Capsicum and turmeric oleoresins increases resistance to necrotic enteritis Br J Nutr110(5)840-7
IL-8
LITAF
TL1A
IL-17
IL-17F
Garlic effects in vitro
Kim DK Lillehoj HS Lee SH Lillehoj EP Bravo D 2013 Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites Br J Nutr 109(1)76-88
a
b
a
460
480
500
520
540
560
580
600
Non-infected Control Garlicon 40
Control E acervulina infected
Body
wei
ght
gai
n (
g)
BW gain
a
b
00
05
10
15
20
25
30
Control Garlicon 40
Oocy
sts
(X10
8 )
Oocysts
b
a
0
02
04
06
08
1
Control Garlicon 40
Ab r
esponse
to p
rofilin
(O
D
450n
m)
Ab-Profilin
In vivo dietary effects of Garlic
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
Son T Camandola S and Mattson M 2008 Hormetic dietary phytochemicals Neuromolecular Med 2008 10236-246
Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
Li Lillehoj et al 2010 Avian Pathology 39255 Li Lillehoj et al 2010 Avian Pathology 39247 Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology In press
Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
19
Kim DK Lillehoj HS 2014 Transcriptional profiles of host-pathogen responses to necrotic enteritis and differential regulation of immune genes in two inbreed chicken lines showing disparate disease susceptibility PLoS ONE 9(12)e114960
Avian Coccidiosis
Coccidiosis are ubiquitous they are present wherever chickens arereared (traditional industrial label or organicbio farms) Nine speciesof Eimeria have been described in chicken
Balance of Th17 and Treg cells in Coccidiosis
Th17 and Treg cells have opposite actions on intestinal immunity
Treg cells suppress a variety of physiological and
pathological immune responses in the intestine
Th17 cells play a key role in intestinal inflammation
through induction of pro-inflammatory cytokines
Dendritic cells (APC) present the antigen to the T cells
Naiumlve CD4+ T cells differentiate into either Th17 or Treg
once in contact with dendritic cells
In gut immune systemhellip
IL-17 as a potential therapeutic target of coccidiosisIL-17
bull is pro-inflammatory cytokine produced by Th17 cells
bull induces various pro-inflammatory cytokines and
mediates inflammatory response
Administration of IL-17A neutralizing antibody induce
- Enhanced weight gain
- Reduced oocyst shedding
- Increased heterophil infiltration
- Reduction of cecal lesion
- Inhibition of E tenella schizont and merozoite development
Del Cacho et al 2014 Zhang et al 2013
Kim WH Jeong J Park AR Yim D Kim S Chang HH Yang SH Kim DH Lillehoj HS Min W 2014 Downregulation of chicken interleukin-17 receptor A during Eimeria infection Infect Immun 82(9)3845-54
Flow diagram for screening immunoactive phytochemicals
Disease challenge
Macrophage activation
Lymphocyte stimulation
Cytokine Tumor cytotoxicity Direct killing of pathogens
Select synergistic plants
Nutrigenomics
In vitro screening
In vivo feeding trial
Randomized Performance analysis in commercial broilers
In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
5 ppmcarvacrol
3 ppmcinnamaldehyde
2 ppmCapsicum oleor
23
246
625198
3126
48
156
31
Primary infectionE Maxima
Secondary infectionE Maxima
Up regulated Down regulated
Kim DK Lillehoj HS Lee S H Jang S and Bravo D 2010 High-Throughput Gene Expression Analysis of Intraepithelial Lymphocytes Following dietary Carvacrol Cinnamaldehyde or Capsicum Oleoresin Poultry Science 8968-81Kim DK Lillehoj HS Min WG Kim CH Hong YH and Lillehoj EP 2011 PlosOne V6e27712
NUTRIGENOMICS to identify 3 phytonutrient combination that reduced negative effects of avian coccidiosis
From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
Phytochemical doses that we used were not cytotoxic to pathogens
Dietary effects of phytonutrients on coccidiosis
Lee S H Kim Duk Kyung Bravo D Lillehoj HS 2010 Journal Poultry Science 4789-95
Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokinetranscripts and mitigated gut damage due to necrotic enteritis
Lee SH et al Lillehoj HS Bravo DM 2013 Dietary supplementation of young broiler chickens with Capsicum and turmeric oleoresins increases resistance to necrotic enteritis Br J Nutr110(5)840-7
IL-8
LITAF
TL1A
IL-17
IL-17F
Garlic effects in vitro
Kim DK Lillehoj HS Lee SH Lillehoj EP Bravo D 2013 Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites Br J Nutr 109(1)76-88
a
b
a
460
480
500
520
540
560
580
600
Non-infected Control Garlicon 40
Control E acervulina infected
Body
wei
ght
gai
n (
g)
BW gain
a
b
00
05
10
15
20
25
30
Control Garlicon 40
Oocy
sts
(X10
8 )
Oocysts
b
a
0
02
04
06
08
1
Control Garlicon 40
Ab r
esponse
to p
rofilin
(O
D
450n
m)
Ab-Profilin
In vivo dietary effects of Garlic
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
Li Lillehoj et al 2010 Avian Pathology 39255 Li Lillehoj et al 2010 Avian Pathology 39247 Oh ST and Lillehoj 2016 The role of host genetic factors and host immunity in necrotic enteritis Avian Pathology In press
Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
19
Kim DK Lillehoj HS 2014 Transcriptional profiles of host-pathogen responses to necrotic enteritis and differential regulation of immune genes in two inbreed chicken lines showing disparate disease susceptibility PLoS ONE 9(12)e114960
Avian Coccidiosis
Coccidiosis are ubiquitous they are present wherever chickens arereared (traditional industrial label or organicbio farms) Nine speciesof Eimeria have been described in chicken
Balance of Th17 and Treg cells in Coccidiosis
Th17 and Treg cells have opposite actions on intestinal immunity
Treg cells suppress a variety of physiological and
pathological immune responses in the intestine
Th17 cells play a key role in intestinal inflammation
through induction of pro-inflammatory cytokines
Dendritic cells (APC) present the antigen to the T cells
Naiumlve CD4+ T cells differentiate into either Th17 or Treg
once in contact with dendritic cells
In gut immune systemhellip
IL-17 as a potential therapeutic target of coccidiosisIL-17
bull is pro-inflammatory cytokine produced by Th17 cells
bull induces various pro-inflammatory cytokines and
mediates inflammatory response
Administration of IL-17A neutralizing antibody induce
- Enhanced weight gain
- Reduced oocyst shedding
- Increased heterophil infiltration
- Reduction of cecal lesion
- Inhibition of E tenella schizont and merozoite development
Del Cacho et al 2014 Zhang et al 2013
Kim WH Jeong J Park AR Yim D Kim S Chang HH Yang SH Kim DH Lillehoj HS Min W 2014 Downregulation of chicken interleukin-17 receptor A during Eimeria infection Infect Immun 82(9)3845-54
Flow diagram for screening immunoactive phytochemicals
Disease challenge
Macrophage activation
Lymphocyte stimulation
Cytokine Tumor cytotoxicity Direct killing of pathogens
Select synergistic plants
Nutrigenomics
In vitro screening
In vivo feeding trial
Randomized Performance analysis in commercial broilers
In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
5 ppmcarvacrol
3 ppmcinnamaldehyde
2 ppmCapsicum oleor
23
246
625198
3126
48
156
31
Primary infectionE Maxima
Secondary infectionE Maxima
Up regulated Down regulated
Kim DK Lillehoj HS Lee S H Jang S and Bravo D 2010 High-Throughput Gene Expression Analysis of Intraepithelial Lymphocytes Following dietary Carvacrol Cinnamaldehyde or Capsicum Oleoresin Poultry Science 8968-81Kim DK Lillehoj HS Min WG Kim CH Hong YH and Lillehoj EP 2011 PlosOne V6e27712
NUTRIGENOMICS to identify 3 phytonutrient combination that reduced negative effects of avian coccidiosis
From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
Phytochemical doses that we used were not cytotoxic to pathogens
Dietary effects of phytonutrients on coccidiosis
Lee S H Kim Duk Kyung Bravo D Lillehoj HS 2010 Journal Poultry Science 4789-95
Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokinetranscripts and mitigated gut damage due to necrotic enteritis
Lee SH et al Lillehoj HS Bravo DM 2013 Dietary supplementation of young broiler chickens with Capsicum and turmeric oleoresins increases resistance to necrotic enteritis Br J Nutr110(5)840-7
IL-8
LITAF
TL1A
IL-17
IL-17F
Garlic effects in vitro
Kim DK Lillehoj HS Lee SH Lillehoj EP Bravo D 2013 Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites Br J Nutr 109(1)76-88
a
b
a
460
480
500
520
540
560
580
600
Non-infected Control Garlicon 40
Control E acervulina infected
Body
wei
ght
gai
n (
g)
BW gain
a
b
00
05
10
15
20
25
30
Control Garlicon 40
Oocy
sts
(X10
8 )
Oocysts
b
a
0
02
04
06
08
1
Control Garlicon 40
Ab r
esponse
to p
rofilin
(O
D
450n
m)
Ab-Profilin
In vivo dietary effects of Garlic
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
19
Kim DK Lillehoj HS 2014 Transcriptional profiles of host-pathogen responses to necrotic enteritis and differential regulation of immune genes in two inbreed chicken lines showing disparate disease susceptibility PLoS ONE 9(12)e114960
Avian Coccidiosis
Coccidiosis are ubiquitous they are present wherever chickens arereared (traditional industrial label or organicbio farms) Nine speciesof Eimeria have been described in chicken
Balance of Th17 and Treg cells in Coccidiosis
Th17 and Treg cells have opposite actions on intestinal immunity
Treg cells suppress a variety of physiological and
pathological immune responses in the intestine
Th17 cells play a key role in intestinal inflammation
through induction of pro-inflammatory cytokines
Dendritic cells (APC) present the antigen to the T cells
Naiumlve CD4+ T cells differentiate into either Th17 or Treg
once in contact with dendritic cells
In gut immune systemhellip
IL-17 as a potential therapeutic target of coccidiosisIL-17
bull is pro-inflammatory cytokine produced by Th17 cells
bull induces various pro-inflammatory cytokines and
mediates inflammatory response
Administration of IL-17A neutralizing antibody induce
- Enhanced weight gain
- Reduced oocyst shedding
- Increased heterophil infiltration
- Reduction of cecal lesion
- Inhibition of E tenella schizont and merozoite development
Del Cacho et al 2014 Zhang et al 2013
Kim WH Jeong J Park AR Yim D Kim S Chang HH Yang SH Kim DH Lillehoj HS Min W 2014 Downregulation of chicken interleukin-17 receptor A during Eimeria infection Infect Immun 82(9)3845-54
Flow diagram for screening immunoactive phytochemicals
Disease challenge
Macrophage activation
Lymphocyte stimulation
Cytokine Tumor cytotoxicity Direct killing of pathogens
Select synergistic plants
Nutrigenomics
In vitro screening
In vivo feeding trial
Randomized Performance analysis in commercial broilers
In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
5 ppmcarvacrol
3 ppmcinnamaldehyde
2 ppmCapsicum oleor
23
246
625198
3126
48
156
31
Primary infectionE Maxima
Secondary infectionE Maxima
Up regulated Down regulated
Kim DK Lillehoj HS Lee S H Jang S and Bravo D 2010 High-Throughput Gene Expression Analysis of Intraepithelial Lymphocytes Following dietary Carvacrol Cinnamaldehyde or Capsicum Oleoresin Poultry Science 8968-81Kim DK Lillehoj HS Min WG Kim CH Hong YH and Lillehoj EP 2011 PlosOne V6e27712
NUTRIGENOMICS to identify 3 phytonutrient combination that reduced negative effects of avian coccidiosis
From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
Phytochemical doses that we used were not cytotoxic to pathogens
Dietary effects of phytonutrients on coccidiosis
Lee S H Kim Duk Kyung Bravo D Lillehoj HS 2010 Journal Poultry Science 4789-95
Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokinetranscripts and mitigated gut damage due to necrotic enteritis
Lee SH et al Lillehoj HS Bravo DM 2013 Dietary supplementation of young broiler chickens with Capsicum and turmeric oleoresins increases resistance to necrotic enteritis Br J Nutr110(5)840-7
IL-8
LITAF
TL1A
IL-17
IL-17F
Garlic effects in vitro
Kim DK Lillehoj HS Lee SH Lillehoj EP Bravo D 2013 Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites Br J Nutr 109(1)76-88
a
b
a
460
480
500
520
540
560
580
600
Non-infected Control Garlicon 40
Control E acervulina infected
Body
wei
ght
gai
n (
g)
BW gain
a
b
00
05
10
15
20
25
30
Control Garlicon 40
Oocy
sts
(X10
8 )
Oocysts
b
a
0
02
04
06
08
1
Control Garlicon 40
Ab r
esponse
to p
rofilin
(O
D
450n
m)
Ab-Profilin
In vivo dietary effects of Garlic
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
Avian Coccidiosis
Coccidiosis are ubiquitous they are present wherever chickens arereared (traditional industrial label or organicbio farms) Nine speciesof Eimeria have been described in chicken
Balance of Th17 and Treg cells in Coccidiosis
Th17 and Treg cells have opposite actions on intestinal immunity
Treg cells suppress a variety of physiological and
pathological immune responses in the intestine
Th17 cells play a key role in intestinal inflammation
through induction of pro-inflammatory cytokines
Dendritic cells (APC) present the antigen to the T cells
Naiumlve CD4+ T cells differentiate into either Th17 or Treg
once in contact with dendritic cells
In gut immune systemhellip
IL-17 as a potential therapeutic target of coccidiosisIL-17
bull is pro-inflammatory cytokine produced by Th17 cells
bull induces various pro-inflammatory cytokines and
mediates inflammatory response
Administration of IL-17A neutralizing antibody induce
- Enhanced weight gain
- Reduced oocyst shedding
- Increased heterophil infiltration
- Reduction of cecal lesion
- Inhibition of E tenella schizont and merozoite development
Del Cacho et al 2014 Zhang et al 2013
Kim WH Jeong J Park AR Yim D Kim S Chang HH Yang SH Kim DH Lillehoj HS Min W 2014 Downregulation of chicken interleukin-17 receptor A during Eimeria infection Infect Immun 82(9)3845-54
Flow diagram for screening immunoactive phytochemicals
Disease challenge
Macrophage activation
Lymphocyte stimulation
Cytokine Tumor cytotoxicity Direct killing of pathogens
Select synergistic plants
Nutrigenomics
In vitro screening
In vivo feeding trial
Randomized Performance analysis in commercial broilers
In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
5 ppmcarvacrol
3 ppmcinnamaldehyde
2 ppmCapsicum oleor
23
246
625198
3126
48
156
31
Primary infectionE Maxima
Secondary infectionE Maxima
Up regulated Down regulated
Kim DK Lillehoj HS Lee S H Jang S and Bravo D 2010 High-Throughput Gene Expression Analysis of Intraepithelial Lymphocytes Following dietary Carvacrol Cinnamaldehyde or Capsicum Oleoresin Poultry Science 8968-81Kim DK Lillehoj HS Min WG Kim CH Hong YH and Lillehoj EP 2011 PlosOne V6e27712
NUTRIGENOMICS to identify 3 phytonutrient combination that reduced negative effects of avian coccidiosis
From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
Phytochemical doses that we used were not cytotoxic to pathogens
Dietary effects of phytonutrients on coccidiosis
Lee S H Kim Duk Kyung Bravo D Lillehoj HS 2010 Journal Poultry Science 4789-95
Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokinetranscripts and mitigated gut damage due to necrotic enteritis
Lee SH et al Lillehoj HS Bravo DM 2013 Dietary supplementation of young broiler chickens with Capsicum and turmeric oleoresins increases resistance to necrotic enteritis Br J Nutr110(5)840-7
IL-8
LITAF
TL1A
IL-17
IL-17F
Garlic effects in vitro
Kim DK Lillehoj HS Lee SH Lillehoj EP Bravo D 2013 Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites Br J Nutr 109(1)76-88
a
b
a
460
480
500
520
540
560
580
600
Non-infected Control Garlicon 40
Control E acervulina infected
Body
wei
ght
gai
n (
g)
BW gain
a
b
00
05
10
15
20
25
30
Control Garlicon 40
Oocy
sts
(X10
8 )
Oocysts
b
a
0
02
04
06
08
1
Control Garlicon 40
Ab r
esponse
to p
rofilin
(O
D
450n
m)
Ab-Profilin
In vivo dietary effects of Garlic
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
Balance of Th17 and Treg cells in Coccidiosis
Th17 and Treg cells have opposite actions on intestinal immunity
Treg cells suppress a variety of physiological and
pathological immune responses in the intestine
Th17 cells play a key role in intestinal inflammation
through induction of pro-inflammatory cytokines
Dendritic cells (APC) present the antigen to the T cells
Naiumlve CD4+ T cells differentiate into either Th17 or Treg
once in contact with dendritic cells
In gut immune systemhellip
IL-17 as a potential therapeutic target of coccidiosisIL-17
bull is pro-inflammatory cytokine produced by Th17 cells
bull induces various pro-inflammatory cytokines and
mediates inflammatory response
Administration of IL-17A neutralizing antibody induce
- Enhanced weight gain
- Reduced oocyst shedding
- Increased heterophil infiltration
- Reduction of cecal lesion
- Inhibition of E tenella schizont and merozoite development
Del Cacho et al 2014 Zhang et al 2013
Kim WH Jeong J Park AR Yim D Kim S Chang HH Yang SH Kim DH Lillehoj HS Min W 2014 Downregulation of chicken interleukin-17 receptor A during Eimeria infection Infect Immun 82(9)3845-54
Flow diagram for screening immunoactive phytochemicals
Disease challenge
Macrophage activation
Lymphocyte stimulation
Cytokine Tumor cytotoxicity Direct killing of pathogens
Select synergistic plants
Nutrigenomics
In vitro screening
In vivo feeding trial
Randomized Performance analysis in commercial broilers
In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
5 ppmcarvacrol
3 ppmcinnamaldehyde
2 ppmCapsicum oleor
23
246
625198
3126
48
156
31
Primary infectionE Maxima
Secondary infectionE Maxima
Up regulated Down regulated
Kim DK Lillehoj HS Lee S H Jang S and Bravo D 2010 High-Throughput Gene Expression Analysis of Intraepithelial Lymphocytes Following dietary Carvacrol Cinnamaldehyde or Capsicum Oleoresin Poultry Science 8968-81Kim DK Lillehoj HS Min WG Kim CH Hong YH and Lillehoj EP 2011 PlosOne V6e27712
NUTRIGENOMICS to identify 3 phytonutrient combination that reduced negative effects of avian coccidiosis
From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
Phytochemical doses that we used were not cytotoxic to pathogens
Dietary effects of phytonutrients on coccidiosis
Lee S H Kim Duk Kyung Bravo D Lillehoj HS 2010 Journal Poultry Science 4789-95
Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokinetranscripts and mitigated gut damage due to necrotic enteritis
Lee SH et al Lillehoj HS Bravo DM 2013 Dietary supplementation of young broiler chickens with Capsicum and turmeric oleoresins increases resistance to necrotic enteritis Br J Nutr110(5)840-7
IL-8
LITAF
TL1A
IL-17
IL-17F
Garlic effects in vitro
Kim DK Lillehoj HS Lee SH Lillehoj EP Bravo D 2013 Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites Br J Nutr 109(1)76-88
a
b
a
460
480
500
520
540
560
580
600
Non-infected Control Garlicon 40
Control E acervulina infected
Body
wei
ght
gai
n (
g)
BW gain
a
b
00
05
10
15
20
25
30
Control Garlicon 40
Oocy
sts
(X10
8 )
Oocysts
b
a
0
02
04
06
08
1
Control Garlicon 40
Ab r
esponse
to p
rofilin
(O
D
450n
m)
Ab-Profilin
In vivo dietary effects of Garlic
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
IL-17 as a potential therapeutic target of coccidiosisIL-17
bull is pro-inflammatory cytokine produced by Th17 cells
bull induces various pro-inflammatory cytokines and
mediates inflammatory response
Administration of IL-17A neutralizing antibody induce
- Enhanced weight gain
- Reduced oocyst shedding
- Increased heterophil infiltration
- Reduction of cecal lesion
- Inhibition of E tenella schizont and merozoite development
Del Cacho et al 2014 Zhang et al 2013
Kim WH Jeong J Park AR Yim D Kim S Chang HH Yang SH Kim DH Lillehoj HS Min W 2014 Downregulation of chicken interleukin-17 receptor A during Eimeria infection Infect Immun 82(9)3845-54
Flow diagram for screening immunoactive phytochemicals
Disease challenge
Macrophage activation
Lymphocyte stimulation
Cytokine Tumor cytotoxicity Direct killing of pathogens
Select synergistic plants
Nutrigenomics
In vitro screening
In vivo feeding trial
Randomized Performance analysis in commercial broilers
In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
5 ppmcarvacrol
3 ppmcinnamaldehyde
2 ppmCapsicum oleor
23
246
625198
3126
48
156
31
Primary infectionE Maxima
Secondary infectionE Maxima
Up regulated Down regulated
Kim DK Lillehoj HS Lee S H Jang S and Bravo D 2010 High-Throughput Gene Expression Analysis of Intraepithelial Lymphocytes Following dietary Carvacrol Cinnamaldehyde or Capsicum Oleoresin Poultry Science 8968-81Kim DK Lillehoj HS Min WG Kim CH Hong YH and Lillehoj EP 2011 PlosOne V6e27712
NUTRIGENOMICS to identify 3 phytonutrient combination that reduced negative effects of avian coccidiosis
From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
Phytochemical doses that we used were not cytotoxic to pathogens
Dietary effects of phytonutrients on coccidiosis
Lee S H Kim Duk Kyung Bravo D Lillehoj HS 2010 Journal Poultry Science 4789-95
Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokinetranscripts and mitigated gut damage due to necrotic enteritis
Lee SH et al Lillehoj HS Bravo DM 2013 Dietary supplementation of young broiler chickens with Capsicum and turmeric oleoresins increases resistance to necrotic enteritis Br J Nutr110(5)840-7
IL-8
LITAF
TL1A
IL-17
IL-17F
Garlic effects in vitro
Kim DK Lillehoj HS Lee SH Lillehoj EP Bravo D 2013 Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites Br J Nutr 109(1)76-88
a
b
a
460
480
500
520
540
560
580
600
Non-infected Control Garlicon 40
Control E acervulina infected
Body
wei
ght
gai
n (
g)
BW gain
a
b
00
05
10
15
20
25
30
Control Garlicon 40
Oocy
sts
(X10
8 )
Oocysts
b
a
0
02
04
06
08
1
Control Garlicon 40
Ab r
esponse
to p
rofilin
(O
D
450n
m)
Ab-Profilin
In vivo dietary effects of Garlic
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
Flow diagram for screening immunoactive phytochemicals
Disease challenge
Macrophage activation
Lymphocyte stimulation
Cytokine Tumor cytotoxicity Direct killing of pathogens
Select synergistic plants
Nutrigenomics
In vitro screening
In vivo feeding trial
Randomized Performance analysis in commercial broilers
In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
5 ppmcarvacrol
3 ppmcinnamaldehyde
2 ppmCapsicum oleor
23
246
625198
3126
48
156
31
Primary infectionE Maxima
Secondary infectionE Maxima
Up regulated Down regulated
Kim DK Lillehoj HS Lee S H Jang S and Bravo D 2010 High-Throughput Gene Expression Analysis of Intraepithelial Lymphocytes Following dietary Carvacrol Cinnamaldehyde or Capsicum Oleoresin Poultry Science 8968-81Kim DK Lillehoj HS Min WG Kim CH Hong YH and Lillehoj EP 2011 PlosOne V6e27712
NUTRIGENOMICS to identify 3 phytonutrient combination that reduced negative effects of avian coccidiosis
From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
Phytochemical doses that we used were not cytotoxic to pathogens
Dietary effects of phytonutrients on coccidiosis
Lee S H Kim Duk Kyung Bravo D Lillehoj HS 2010 Journal Poultry Science 4789-95
Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokinetranscripts and mitigated gut damage due to necrotic enteritis
Lee SH et al Lillehoj HS Bravo DM 2013 Dietary supplementation of young broiler chickens with Capsicum and turmeric oleoresins increases resistance to necrotic enteritis Br J Nutr110(5)840-7
IL-8
LITAF
TL1A
IL-17
IL-17F
Garlic effects in vitro
Kim DK Lillehoj HS Lee SH Lillehoj EP Bravo D 2013 Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites Br J Nutr 109(1)76-88
a
b
a
460
480
500
520
540
560
580
600
Non-infected Control Garlicon 40
Control E acervulina infected
Body
wei
ght
gai
n (
g)
BW gain
a
b
00
05
10
15
20
25
30
Control Garlicon 40
Oocy
sts
(X10
8 )
Oocysts
b
a
0
02
04
06
08
1
Control Garlicon 40
Ab r
esponse
to p
rofilin
(O
D
450n
m)
Ab-Profilin
In vivo dietary effects of Garlic
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
5 ppmcarvacrol
3 ppmcinnamaldehyde
2 ppmCapsicum oleor
23
246
625198
3126
48
156
31
Primary infectionE Maxima
Secondary infectionE Maxima
Up regulated Down regulated
Kim DK Lillehoj HS Lee S H Jang S and Bravo D 2010 High-Throughput Gene Expression Analysis of Intraepithelial Lymphocytes Following dietary Carvacrol Cinnamaldehyde or Capsicum Oleoresin Poultry Science 8968-81Kim DK Lillehoj HS Min WG Kim CH Hong YH and Lillehoj EP 2011 PlosOne V6e27712
NUTRIGENOMICS to identify 3 phytonutrient combination that reduced negative effects of avian coccidiosis
From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
Phytochemical doses that we used were not cytotoxic to pathogens
Dietary effects of phytonutrients on coccidiosis
Lee S H Kim Duk Kyung Bravo D Lillehoj HS 2010 Journal Poultry Science 4789-95
Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokinetranscripts and mitigated gut damage due to necrotic enteritis
Lee SH et al Lillehoj HS Bravo DM 2013 Dietary supplementation of young broiler chickens with Capsicum and turmeric oleoresins increases resistance to necrotic enteritis Br J Nutr110(5)840-7
IL-8
LITAF
TL1A
IL-17
IL-17F
Garlic effects in vitro
Kim DK Lillehoj HS Lee SH Lillehoj EP Bravo D 2013 Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites Br J Nutr 109(1)76-88
a
b
a
460
480
500
520
540
560
580
600
Non-infected Control Garlicon 40
Control E acervulina infected
Body
wei
ght
gai
n (
g)
BW gain
a
b
00
05
10
15
20
25
30
Control Garlicon 40
Oocy
sts
(X10
8 )
Oocysts
b
a
0
02
04
06
08
1
Control Garlicon 40
Ab r
esponse
to p
rofilin
(O
D
450n
m)
Ab-Profilin
In vivo dietary effects of Garlic
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
5 ppmcarvacrol
3 ppmcinnamaldehyde
2 ppmCapsicum oleor
23
246
625198
3126
48
156
31
Primary infectionE Maxima
Secondary infectionE Maxima
Up regulated Down regulated
Kim DK Lillehoj HS Lee S H Jang S and Bravo D 2010 High-Throughput Gene Expression Analysis of Intraepithelial Lymphocytes Following dietary Carvacrol Cinnamaldehyde or Capsicum Oleoresin Poultry Science 8968-81Kim DK Lillehoj HS Min WG Kim CH Hong YH and Lillehoj EP 2011 PlosOne V6e27712
NUTRIGENOMICS to identify 3 phytonutrient combination that reduced negative effects of avian coccidiosis
From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
Phytochemical doses that we used were not cytotoxic to pathogens
Dietary effects of phytonutrients on coccidiosis
Lee S H Kim Duk Kyung Bravo D Lillehoj HS 2010 Journal Poultry Science 4789-95
Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokinetranscripts and mitigated gut damage due to necrotic enteritis
Lee SH et al Lillehoj HS Bravo DM 2013 Dietary supplementation of young broiler chickens with Capsicum and turmeric oleoresins increases resistance to necrotic enteritis Br J Nutr110(5)840-7
IL-8
LITAF
TL1A
IL-17
IL-17F
Garlic effects in vitro
Kim DK Lillehoj HS Lee SH Lillehoj EP Bravo D 2013 Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites Br J Nutr 109(1)76-88
a
b
a
460
480
500
520
540
560
580
600
Non-infected Control Garlicon 40
Control E acervulina infected
Body
wei
ght
gai
n (
g)
BW gain
a
b
00
05
10
15
20
25
30
Control Garlicon 40
Oocy
sts
(X10
8 )
Oocysts
b
a
0
02
04
06
08
1
Control Garlicon 40
Ab r
esponse
to p
rofilin
(O
D
450n
m)
Ab-Profilin
In vivo dietary effects of Garlic
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
Phytochemical doses that we used were not cytotoxic to pathogens
Dietary effects of phytonutrients on coccidiosis
Lee S H Kim Duk Kyung Bravo D Lillehoj HS 2010 Journal Poultry Science 4789-95
Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokinetranscripts and mitigated gut damage due to necrotic enteritis
Lee SH et al Lillehoj HS Bravo DM 2013 Dietary supplementation of young broiler chickens with Capsicum and turmeric oleoresins increases resistance to necrotic enteritis Br J Nutr110(5)840-7
IL-8
LITAF
TL1A
IL-17
IL-17F
Garlic effects in vitro
Kim DK Lillehoj HS Lee SH Lillehoj EP Bravo D 2013 Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites Br J Nutr 109(1)76-88
a
b
a
460
480
500
520
540
560
580
600
Non-infected Control Garlicon 40
Control E acervulina infected
Body
wei
ght
gai
n (
g)
BW gain
a
b
00
05
10
15
20
25
30
Control Garlicon 40
Oocy
sts
(X10
8 )
Oocysts
b
a
0
02
04
06
08
1
Control Garlicon 40
Ab r
esponse
to p
rofilin
(O
D
450n
m)
Ab-Profilin
In vivo dietary effects of Garlic
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
Dietary effects of phytonutrients on coccidiosis
Lee S H Kim Duk Kyung Bravo D Lillehoj HS 2010 Journal Poultry Science 4789-95
Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokinetranscripts and mitigated gut damage due to necrotic enteritis
Lee SH et al Lillehoj HS Bravo DM 2013 Dietary supplementation of young broiler chickens with Capsicum and turmeric oleoresins increases resistance to necrotic enteritis Br J Nutr110(5)840-7
IL-8
LITAF
TL1A
IL-17
IL-17F
Garlic effects in vitro
Kim DK Lillehoj HS Lee SH Lillehoj EP Bravo D 2013 Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites Br J Nutr 109(1)76-88
a
b
a
460
480
500
520
540
560
580
600
Non-infected Control Garlicon 40
Control E acervulina infected
Body
wei
ght
gai
n (
g)
BW gain
a
b
00
05
10
15
20
25
30
Control Garlicon 40
Oocy
sts
(X10
8 )
Oocysts
b
a
0
02
04
06
08
1
Control Garlicon 40
Ab r
esponse
to p
rofilin
(O
D
450n
m)
Ab-Profilin
In vivo dietary effects of Garlic
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokinetranscripts and mitigated gut damage due to necrotic enteritis
Lee SH et al Lillehoj HS Bravo DM 2013 Dietary supplementation of young broiler chickens with Capsicum and turmeric oleoresins increases resistance to necrotic enteritis Br J Nutr110(5)840-7
IL-8
LITAF
TL1A
IL-17
IL-17F
Garlic effects in vitro
Kim DK Lillehoj HS Lee SH Lillehoj EP Bravo D 2013 Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites Br J Nutr 109(1)76-88
a
b
a
460
480
500
520
540
560
580
600
Non-infected Control Garlicon 40
Control E acervulina infected
Body
wei
ght
gai
n (
g)
BW gain
a
b
00
05
10
15
20
25
30
Control Garlicon 40
Oocy
sts
(X10
8 )
Oocysts
b
a
0
02
04
06
08
1
Control Garlicon 40
Ab r
esponse
to p
rofilin
(O
D
450n
m)
Ab-Profilin
In vivo dietary effects of Garlic
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
Garlic effects in vitro
Kim DK Lillehoj HS Lee SH Lillehoj EP Bravo D 2013 Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites Br J Nutr 109(1)76-88
a
b
a
460
480
500
520
540
560
580
600
Non-infected Control Garlicon 40
Control E acervulina infected
Body
wei
ght
gai
n (
g)
BW gain
a
b
00
05
10
15
20
25
30
Control Garlicon 40
Oocy
sts
(X10
8 )
Oocysts
b
a
0
02
04
06
08
1
Control Garlicon 40
Ab r
esponse
to p
rofilin
(O
D
450n
m)
Ab-Profilin
In vivo dietary effects of Garlic
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
- Allium hookeri a member of the family Alliaceae is found in Ceylon Greece Southern China and India and has been used by locals to treat cough and cold and to heal burns and wounds(Sharma et al 2011)
- A hookeri contains an abundance of organo-sulphur compounds volatile sulphur compounds proteins prostaglandins fructans vitamins and polyphenols as well as Allicin
- Allicin and organic sulphur compounds are known to reduce cholesterol levels decrease the risk of heart attack and exert anti-inflammatory effects (Bae and Bae 2012 Kim et al 2012)
Allium hookeri
0
20
40
60
80
100
1000 500 250 125 625 1000 500 250 125 625 1000 500 250 125 625(μgmL)
Scav
engi
ng a
ctiv
ity (
)
Vit CControl Root Fermented rootLeaf
Free radical scavenging capacity
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
Interplay of nutrition gut microbiota and immunity
Dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
Effect of phytochemicals on gut microbiota diversity in broilers
0
10
20
30
40
50
60
70
80
90
100
Variovorax
Geitlerinema
Calothrix
Clostridium
Selenihalanaerobacter
Streptococcus
Candidatus Arthromitus
Lactobacillus
Cobb Hubbard Ross
Kim JE Lillehoj HS Bravo D 2015 Dietary capsicum and curcuma longa oleoresins increase intestinal microbiome and necrotic enteritis in three commercial broiler breeds Res vet sci 102150-158
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
From plants to novel anti-parasite therapiesThe 2015 Nobel Prize winner in Medicine to Dr Youyou Tu concerning novel therapies against infections caused by Malaria protozoa
Malaria-mosquito-borne disease caused by single-cell parasites which invade red blood cells causing fever and in severe cases brain damage and death It claims more than 450000 lives
Strong evidence to suggest that the primary activator is an iron source Multi-faceted nature of cellular response to artemisinin in Plasmodia and tumor cells includes DNA damage which is dose dependent
-Resistance-Bioavailability-Cost and limitation-Mechanism of action
- Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals Mode of action in modulating cross-talks among immunity disease resistance and gut microbiota
- Slide Number 2
- Slide Number 3
- Antibiotics as growth promotersMany different types of pathogens infect chickens during their lifetime Use of antibiotics is increasing
- Signs of poor gut health
- Slide Number 6
- Slide Number 7
- Dysbiosis and subclinical enteritis
- Low-level effect of antibiotic growth promoters on body weight gains in broilers(Oh ST and Lillehoj HS 2017)
- Beneficial effects of antibiotic alternatives
- Slide Number 11
- Slide Number 12
- Antibiotic alternatives-Mechanisms
- Slide Number 14
- Slide Number 15
- Slide Number 16
- Hormesis is a biological phenomenon whereby a beneficial effect (improved health stress tolerance growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses
- Outbreaks of Clostridial infections have been associated with certain drug use disruption in gut microbiota gut barrier failure bacterial translocation inflammation and acute death
- Host intestinal genes differentially affected by Necrotic enteritis in broiler chickens
- Avian Coccidiosis
- Slide Number 21
- Slide Number 22
- Flow diagram for screening immunoactive phytochemicals
- In vitro and in vivo effects of purified phytochemicals on Eimeria and C perfringens
- Slide Number 25
- From black box to bold scienceLee Sung Hyen et al 2011 British J Nutrition
- Slide Number 27
- Dietary Capsicum and turmeric oleoresins decreased inflammatory cytokine transcripts and mitigated gut damage due to necrotic enteritis
- Slide Number 29
- Slide Number 30
- Slide Number 31
- Slide Number 32
- Slide Number 33
- Slide Number 34
- Slide Number 35
-
