Developing a gut health solution - DSM · 24/8/2015 · August 24, 2015 Developing a gut health...
Transcript of Developing a gut health solution - DSM · 24/8/2015 · August 24, 2015 Developing a gut health...
August 24, 2015
Developing a gut health solution
requires a new holistic approach
Arie K. Kies
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Why are we interested?
• DSM: technical solid company; lots of nutrition knowledge
• We want to strengthen support to customers further
Providing solutions according to their needs
Through bright science
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• Reducing use of antibiotics (improving gut health)
• …
Problems of customers?
Focus within poultry-feed industry:
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State of affairs• Efficacy AGP
• Risks
• Effect of termination
• Research (opportunities)– Genomics
– Immune modulation
• Alternatives– Pre- and probiotics
– Acids
– Enzymes
– Botanicals
– Bacteriophages
2005
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State of affairs
2015
• Research – Genomics
– Immune modulation
– Microbiomics
• Alternatives– Pre- and probiotics
– Acids
– Enzymes
– Botanicals
– Bacteriophages?
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State of affairs
• Little progress – Reducing AGP’s
– Improving gut health
• Do we look to the right things?
A different angle is required
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Approach so far
“AGP alternatives are being sought to improve health,
immune status and performance in animal agriculture.”
“Most AGP alternatives try to prevent proliferation of
pathogenic bacteria and modulate indigenous bacteria
so that the health, immune status and performance are
improved.”
“While the industry is focused on developing solutions that
work similarly, AGPs' exact mode of action is not yet fully
understood.”
Mallo, Feed International, 2015
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Approach so far
“AGP alternatives are being sought to improve health,
immune status and performance in animal agriculture.”
“Most AGP alternatives try to prevent proliferation of
pathogenic bacteria and modulate indigenous bacteria
so that the health, immune status and performance are
improved.”
“While the industry is focused on developing solutions that
work similarly, AGPs' exact mode of action is not yet fully
understood.”
Mallo, Feed International, 2015
Why?
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Approach so far
“AGP alternatives are being sought to improve health,
immune status and performance in animal agriculture.”
“Most AGP alternatives try to prevent proliferation of
pathogenic bacteria and modulate indigenous bacteria
so that the health, immune status and performance are
improved.”
“While the industry is focused on developing solutions that
work similarly, AGPs' exact mode of action is not yet fully
understood.”
Mallo, Feed International, 2015
Why?
Possible?
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Approach so far
“AGP alternatives are being sought to improve health,
immune status and performance in animal agriculture.”
“Most AGP alternatives try to prevent proliferation of
pathogenic bacteria and modulate indigenous bacteria
so that the health, immune status and performance are
improved.”
“While the industry is focused on developing solutions that
work similarly, AGPs' exact mode of action is not yet fully
understood.”
Mallo, Feed International, 2015
Possible?
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Mode of action of AGP’s?
• How to explain consistent positive effect of AGP’s?• Still consistent in modern diets?
• Do we know what we are looking for??
Change in – microbial population?
– microbial activity?
– development intestine?
• AGP’s are not strain-specific
• AGP’s are usually dosed below MIC
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Mode of action of AGP’s?
AGP’s are not strain-specific
Example Avilamycin (MIC90-values)
Clostridium spp. (+) 8 (µg/ml)
Bifidobacterium spp. (+) 32
Lactobacillus spp. (+) > 128
E. Coli (-) > 128
Bacteroides fragilis (-) 32 (normally commensal)
Enterococcus spp. (+) 4 (lactobacilli-order)
FDA, 2015
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Mode of action of AGP’s?
AGP’s usually dosed below MIC
Again Avilamycin as example
- Max. dose allowed in feed was 10 ppm
- Assume 5-10* dilution in small intestine
concentration (max.) 1-2 µg/ml
[MIC90 Clostridiae: 8 µg/ml]
Specificity and MIC90-values alternatives?
Place (in g.i.t.) of activity?
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Mode of action of AGP’s?
Koopman, 1999
A balanced, stable microflora protects against pathogensNumber Salmonellae/g fresh feces
Problem not pathogens but dysbiosis
- Germfree mice
- Measured with culturing
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Gastrointestinal Microbes of chickens
Schokker, unpublished
Microflora is dynamic. Effect of age:
Enterobacteriaceae (Escherichia, …)
Enterococceae (Lactobacilli)
Clostridiaceae
Lactobacilaceae
Streptococcaceae
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Gastrointestinal Microbes of chickens
Schokker, unpublished
Microflora is dynamic. Effect of age:
Enterobacteriaceae (Escherichia, …)
Enterococceae (Lactobacilli)
Clostridiaceae
Lactobacilaceae
Streptococcaceae
Need to develop balanced gut ecosystem
May vary in time!
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Gut health solution
Improving gut health more consistently:
- Last 10 years products developed that aid overcoming
the “AGP-gap”
- Lack of consistent improvement in many products
- Wet litter is still a recurrent issue
- Despite a lot of (scientific) work
- Too little progress made
- (Too) little interdisciplinary research
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Gut health solution
Improving gut health more consistently:
How to go on?
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Gut health solution
Improving gut health more consistently:
Holistic approach
Gut health: - A complex system
- A complex problem
- Many different angles; different competences
Input from different disciplines required!
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Gut health solution
A complex system -- interactions within the gut
Nutrition
Management, Environment, Genotype
Excretion
Nutrient utilization Immune competence
Performance
gutnutrition genotype
microbiota
From: Smits, 2013
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Gut health solution
Improving gut health more consistently:
Holistic approach (farm perspective)
• Farm management
• Genetics
• Quality day-old chicks
• Feed- Feeding schedule
- Quantity
- Form (particle size; mash vs. pellets)
- Composition (feedstuffs, level)
- Additives
• …
Specific solution required per farm / company!
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Gut health solution
Form (particle size; mash vs. pellets)
But: caecal microbial diversity lower …
Day 0 - 34 Fine Coarse
Feed Intake (g/b) 2991 3144
BW gain (g/b) 1730 1877
Water intake (g/b) 5445 5305
Gizzard weight (g/100 g BW) 1.36 1.60
Villus height (µm) 1517 1840
Crypt depth (µm) 292 230
Qaisrani et al., Poultry Sci. 2014; Qaisrani, 2014
RSM-based diet (‘badly’ digestible protein; different levels)
2 studies
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Gut health solution
Additives
• “… Vitamin A in the womb determines … life-long immunity”
• “… immune health in adulthood can be preset by nutritional status
during fetal life”
Bird, Nature Rev. Immunol., 2014
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Gut health solution
Additives
Brown et al., Immunity, 2015
“- Retinoic acid (RA) stabilizes Th1 fate commitment
- RA-RAR prevents development of pathogenic Th17 cells in vivo”
“Good”
“Bad”
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Gut health solution
Improving gut health more consistently:
Holistic approach (scientific disciplines perspective)
• Animal nutrition
• Human nutrition
• Veterinary science
• Human medical sciences
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Human medical sciences?
- Clostridium perfringens Necrotic enteritis
- Aetiology similar to C. difficile in humans• Organism itself: non-invasive
• Since 2000 dramatic increase severe cases (2/3 hospital acquired)
– “Most important risk factor for C. difficile infection remains antibiotic
use” [!!]
– “Minimizing antibiotics use reduced infection rate by 77% (in a 450-bed
hospital, Scotland)”
– Treatment: antibiotics
– Prevention probiotics? “… not recommended [at this moment]”, but:
“fecal microbiota transplantation seems very promising”
Leffler and Lamont, NEJM 2015
PageVan Nood et al., NEJM 2013
Human medical sciences?
Fecal microbiota transplantation
Rates of cure:
Patients without relapse
for recurrent Clostridium
difficile infection
Also microbiota diversity
increased dramatically by
fecal transplantation
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Gut health solution
Improving gut health more consistently:
Holistic approach (scientific perspective)
• Nutrition– Protein, energy, …
• Feed technology– Milling, pelleting, extrusion, …
• Physiology– Digestion, utilization, …
• Immunology– Immune competence, inflammation, …
• Microbiology– Strains, numbers, …
• “Omics”– Genomics, microbiomics, metabolomics, …
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Gut health solution
Practice: reducing protein often effective
But protein is required
Wijtten et al., Poultry Sci., 2004
♂
♀
CP: ~21 - ~27%
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Gut health solution
Practice: reducing protein often effective
Fermentation of undigested protein
Qaisrani, 2014
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Gut health solution
Practice: reducing protein often effective
Fermentation of undigested protein
Metabolites– Biogenic amines
– Branched chain fatty acids
– Phenols, thiols, ammonia, indoles, …
– Nitrate
• Are they negative by definition?
• Interaction with fermentable carbohydrates
M’Sadeq et al., An. Nutr., 2015
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Metabolomics: big data
>200.000 features for negative scan mode
and
>200.000 for positive, total ± 450.000
Filter 1: ± 80.000 left
Filter 2
Metabolites
identified:
1000
Mass spectrometry Bioinformatics pipeline
MetabolitesAnim
als
on d
iffe
rent
die
ts
Correlations between diet,
intestinal phenotype and
metabolites/microbial species
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Program with different university-groups
- Animal nutrition
- Human medical research
- Veterinary
- Metabolomics
- Microbiology
- …
Understanding animal gut health; emphasis on undigested, fermented
protein, in relation to energy
Impact microbial activity on dysbiosis
Influence of nutritional interactions (feed composition, quality of
ingredients, technology, additives, …)
Gut health solution – our holistic approach
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The DSM gut health solution
Created for customers,
driving by science