The SCIENCE behind the latest

recommendations on prebiotics

in allergy

20 October 2016 KUALA LUMPUR

Johan Garssen, PhD, MDProfessor “Immunopharmacology”

• CVDs

• Diabetes/Obesity

• Cancer

• COPD/ASTHMA

• Autoimmunity

• IBD

• Brain/Behaviour disorders

(autism/parkinsons/alzheimers/depression…)

• Allergies

• HIV (therapy related NCD)

• Ageing/Immunosenescence

• …

• Altered environmental diversity (dysbiosis)?

• Altered lifestyle?

• Industrial technologies?

• Altered antigen/allergen exposure?

• Pollution?

• Dietary changes?

• Microbial exposure hypothesis?

• Change in infectious triggers?

• ???

No change in genes!!

Key role for immune system!!

Why are NCDs so increasingly common?

Defence against pathogens: bacteria, viruses, parasites, fungi

Assistance in anti-cancer responses

Removal of foreign / non-self compounds

Inhibition self-reactive / auto-reactive responsiveness

[Impairment of “auto-immunity” (SLE, MS, RA,…)]

Inhibition “over-activity/allergy” (mucosal and systemic tolerance)

Regulation metabolism (immuno-metabolism)

Tissue repair

Barrier regulation (gut, respiratory tract, brain, placenta, liver, thymus,

kidney)

Major tasks Immune System

Granulocyte

Macrophage / Monocyte

Dendritic cell

T Lymphocyte

(Th1, Th2, Th3, Tr, ...)

B Lymphocyte / Antibodies

Natural Killer Cell

Epithelial cell

Bone marrow

Lymph nodes

Spleen

Thymus

Organs Cells

Neurons, nerves

60-70% of “immune cells” localized in the

gastro-intestinal tract

Immune System

The GUT:

A Complex Neuro-Endocrine-Immune Organ

60 -70% of immune cells

Surface of approximately

300m2

100 million neurons

100 trillion bacteria

“ Gut Microbiota”

Dietary intervention as a tool for ‘immune’ regulation

(inflammation management)?

Utrecht University

Kraneveld, Nijkamp and Garssen 2009, EJP

Rietdijk, van Wezel, Garssen and Kraneveld 2016, Neuroimmunology Neuroinflammation

Immune regulation in the gut

CROSS TALK

years0 1 2 5 10 40 50 60 70 80 90

Th 1

Th 2

Th1 and Th2 activity as function of age

Belinda Van’t Land, Günther Boehm, Johan Garssen:

Breast milk: components with immune modulating potential and their possible role in immune mediated disease resistance.

In Dietary Components and Immune Function, Series: Nutrition and Health. Editors, Watson, Ronald R.; Zibadi, Sherma; Preedy, Victor R. 2011

• Genes

• Hygiene

• Antibiotics

• C-section

• Microbiota

• Drugs

• Diets

• Stress

• Hormones

• Infections

• Cancer

• …

Allergy

Immune fitness

a healthy balance

Inflammation management

ARTHRITIS

INFECTIONS

ALLERGIES

DIABETES, OBESITY

NEC

IMMUNOSENESENCE

CANCERCACHEXIA

COPD

AUTISM

ALZHEIMERPARKINSON

Significant increase in

immune related disorders:

•Allergies, Asthma

•Autoimmunities

•IBD

•ADHD/AUTISM

•Obesity

•Diabetes

•Metab. syndrome

•…

•…

Inverse relationship between the incidence of infectious disease (top) and immune disease

(bottom) from 1950 to 2000. (Jean-Francois Bach/NEJM)

Programmed early in life?!

Th1 , Th2 , Th1/Th2

Th1

Th2 (type I allergy)

Th2

Th2

Th1

Th1 ?

Th1

Th1

Th1 , Th2

HIV

COPD

Allergies

Asthma

Atopic eczema

Coeliac disease

Cystic Fibroses

Cancer

Elderly

Infants

i

n

f

l

a

m

m

a

t

i

o

n

Autoimmunities Th1 , Th2

Immune dysregulation and NCDs

Role in metabolic disorders/diabetes/syndrome X/ obesity: immunometabolism

Role in cachexia/sarcopenia

Role in neurological disorders: Autism, Alzheimer, Depression, Hyperactivity Syndrome, ...

Utrecht University

Hyper immune- responsiveness:

Allergy

Autoimmunity

Chronic inflammatory diseases

Hypo immune- responsiveness:

Infections

Tumors/metastasis

Immune disorders and NCDs

Global Health-WUN

(2014, 2015, 2016, 2017) Cape Town, Frankfurt, Maastricht, New York

Inflammation

(management)

• Altered environmental diversity (dysbiosis)?

• Altered lifestyle?

• Industrial technologies?

• Altered antigen/allergen exposure?

• Pollution?

• Dietary changes?

• Microbial exposure hypothesis?

• Change in infectious triggers?

• ???

Why are NCDs so increasingly common?

Increased pro-inflammatory diet?

Decreased microbial

diversity?Inhaled pollutants?

S. Prescott, Perth, Australia

PREVENTION OF NCDs

Early life: Setting the Right Course for Later Life

CONCEPTION TODDLERHOOD ADULTHOOD

-9m to 24mCritical window of

opportunity to support

healthy later life

Altered growthand development

Stunting

Allergy

Obesity

Coronary heart

disease

Diabetes

Cognitive decline

HEALTHY

DISEASE

Immune Programming

years0 1 2 5 10 40 50 60 70 80 90

Th 1

Th 2

Th1 and Th2 activity as function of age

Belinda Van’t Land, Günther Boehm, Johan Garssen:

Breast milk: components with immune modulating potential and their possible role in immune mediated disease resistance.

In Dietary Components and Immune Function, Series: Nutrition and Health. Editors, Watson, Ronald R.; Zibadi, Sherma; Preedy, Victor R. 2011

• Genes

• Hygiene

• Microbiota

• Drugs

• Diets

• Stress

• Hormones

• Infections

• Cancer

• …

Allergy

Immune fitness/balance

Ability to Adapt

Activation

Pro-inflammation

(Oral) Tolerance

Anti-inflammation

Pathogenic bacteria

Virusses

Parasites

Commensal bacteria (microbiota)

Food antigens

Environmental antigens

TregsTh1/Th2

Th17

R. Kelishadi, S. Farajian. Adv Biomed Res. 2014; 3 The protective effects of breastfeeding on chronic non-communicable diseases in

adulthood: A review of evidence

Energy

Growth

Immunity

Signaling

Proteins

HMOS

An Orchestra of Complex Functions in a Complex Matrix

COMPOSITION & BENEFITS OF HUMAN MILK

Fat / LCPUFA

Lactose

Microbiota

Immunity

Digestion

Nucleotides

Minerals

Vitamins

Bacteria

+ 88% Water

Energy

Immunity

Brain

GrowthImmunityBrain

Microbiota

Immunity

Digestion

Hydration

Immunity…

GrowthImmunity

GrowthBone & TeethBlood

Hormons

GrowthMood

Living Cells

1. Microbiome management (Pro-, Pre-, Syn-, Post-

biotics)

2. Epitopes

3. Antigens/Allergens

4. lcPUFAs

5. Exosomes/lipid vesicles

6. Amino-acids

7. Enzymes

8. Peptides

9. …

New nutritional concepts for immune

development/inflammation management

early in life

IMPACT FOR ALLERGIES

1886

2016

1900s

1920s

1950s

T Escherich

Microbiota

in BF infants

E Moro

H Tissier

Bifidus

in BF infants

P György

HMOS as

Bifidus factor

1960s

1980s

1990s

1970s

Kunz HPAEC

Thurl HPAEC

Stahl MALDI for OS

Stahl sc/lc HMOS

Thurl 4 groups

2000s

Morrow Anti-infection

Kunz Immunmodulation

Newburg Antiifection

Martin Bifidus and Lb in HM

Sela Bifidus enzymes…..

CHO in milks differ

Eschbach

Deniges

HMOS

building blocks

Schönfeld

Polonowski

Lespagnol

First separation

of HMOS

Kuhn

3 groups

of HMOS

Kobata

Characterisation

of sc HMOS

Montreuil

Kobata

Egge FAB MS

Adapted from:

Bode L, Review, Glycobiology vol. 22 no. 9 pp. 1147–1162, 2012

Kunz C Adv Nutr. 2012 May; 3(3): 430S–439S

Kobata A Proc Jpn Acad Ser B Phys Biol Sci. 2010 July 21; 86(7): 731–747

PRE-PRO-BIOTICS & PEDIATRICS ≈ 130 Y

Nutr

icia

Re

se

arc

h©

A PRE-biotic is non-digestible food ingredient that, when consumed in sufficient amounts, selectively stimulates the growth and/or activity of one or a limited number of microbes in the colon resulting in documented health benefits

Examples:

Galacto-Oligosaccharides

Fructo-Oligosaccharides

Inulin

HMOS

...

DRY MATTER OF HUMAN MILK

30-50 g/l

8-10 g/l

PrebioticHMOS

adapted from:

Newburg DS, Neubauer SH: In: RG Jensen (ed):

Human milk composition Academic Press 1995; 273-349

10-12 g/l

HMOS: ESTIMATED > 1000 STRUCTURES

Mass Spec of HMOS

Stahl B, Thurl S, et al. Analyt. Biochem. 1994; 223:218-226

Th1 , Th2 , Th1/Th2

Th1

Th2 (type I allergy)

Th2

Th2

Th1

Th1 ?

Th1

Th1

Th1 , Th2

HIV

COPD

Allergies

Asthma

Atopic eczema

Coeliac disease

Cystic Fibroses

Cancer

Elderly

Infants

i

n

f

l

a

m

m

a

t

i

o

n

Autoimmunities Th1 , Th2

Immune dysregulation and NCDs

Experimental Setup

!!

HMOS reduces diabetes incidence in later life

Diabetes development Urine glucose score results

Food intake & body weight were similar

between experimental groups

0 2 4 6 8 1 0 1 2 1 4 1 6 1 8 2 0 2 2 2 4 2 6 2 8 3 0

0

2 0

4 0

6 0

8 0

1 0 0

W e e k s o f fo llo w -u p

Dia

be

tes

-fre

e s

urv

iva

l (%

)

C o n tro l (n = 1 9 )

H M O S (n = 2 0 )

p = 0 .0 2 6

D ia te r y

in te r v e n t io n

C o n tr o l H M O S

0

1

2

3

4

5

Me

an

no

rm

ali

ze

d

ins

uli

tis

so

co

re

p < 0 .0 0 1

Normalized score (range 0-4)

What Are the Possible Mechanims?

HMOS

T1DImmune System

Adaptive

Innate

Gut Microbiota

Genetics

?

C o n tr o l H M O S

0

5

1 0

1 5

2 0

% C

D2

5 o

f C

D4

ce

lls

p = 0 .0 1

Reduced Overall Immune Hyperactivation

Induction of Immune fitness

c o n tr o l H M O S

0

5

1 0

1 5

2 0

p = 0 .0 3

% C

D6

9 o

f C

D4

ce

lls

C o n tr o l H M O S

0

1 0

2 0

3 0

4 0

Se

ru

m I

L-1

7 (

pg

/mL

)

p = 0 .0 2

What Are the Possible Mechanims?

HMOS

T1DImmune System

Adaptive

Innate

Gut Microbiota

Genetics

?

Second point End point

Dietary intervention

start

First point

4 weeks after

dietary intervention

20 weeks after

dietary intervention

Time points of fecal sample collection

0 2 4 6 8 1 0 1 2 1 4 1 6 1 8 2 0 2 2 2 4 2 6 2 8 3 0

0

2 0

4 0

6 0

8 0

1 0 0

W e e k s o f fo llo w -u p

Dia

be

te

s-fre

e s

urv

iva

l (%

)

C o n tro l (n = 1 9 )

H M O S (n = 2 0 )

p = 0 .0 2 6

D ia te r y

in te r v e n t io n

F ir s t p o in t S e c o n d p o in t E n d p o in t

Changes of phylum distribution of fecal samples over time

Second point

End point

Control diet HMOS diet

First point

Mora Murri et al., 2013

Ratio of Firmicutes/Bacteroidetes in diabetic and healthy

individuals

The Ratio of Firmicutes/Bacteroidetes declined over time in the individuals

who developed T1D, while the inverse pattern was observed in the healthy

individuals.

Negative correlation between this ratio and the glucose levels in children

with T1D.

Ling X, Astrid H, et. al. Submitted 2016

Hypothetical interplay between gut microbiota and intestinal

immune system by HMOS

Bacterial components

(i.e. LPS)

HMOS activate Tregs with anti-inflammatory properties.

HMOS decrease antigen exposure to the mucosal system .

HMOS beneficilally induce toleragenic DCs differentiation.

HMOS increase mucin synthesis therefore maintain gut intergrity and inhibit pathogen adhension.

Conclusions Early HMOS diet suppresses

autoimmune diabetes development in

NOD mice later in life.

Associated with milder insulitis, lower

induction of Th1 cells, overall immune

activation markers expression and down-

regulation of serum IL-17.

Maybe related to regulation of intestinal

microbiota.

HMOS in early life modulate T1D in

later life: an example of immunological

programming.

WIRM award

2016 DAVOS

Vos AP, Haarman M, Buco A, Govers M, Knol J, Garssen J, Stahl B, Boehm G, M'rabet L. Int Immunopharmacol. 2006;6(8):1277-86

2% 2% 2% 2%

0

20

40

60

80

100

120

140

160

Cell

ula

r im

mu

nit

y (

DT

H)

Flu

va

cc

ina

tio

n r

es

po

nse

(1

0-3

mm

)

*

NOT ALL PREBIOTICS ARE THE SAME

0.8

g/100ml

(n=27)

0

g/100ml

(n=33)

0.4

g/100ml

(n=30)

log 1

0 o

f C

FU

/g w

et

faeces (

media

n, IQ

R)

2

3

4

5

6

7

8

9

10

11

12

Reference range (IQR) of breastfed infants (n=15)

Group difference according to Mann-Whitney U-test: * p<0.05 vs. 0.0, # vs. 0.4

**#

Unique oligosaccharides PROMOTE HEALTHY

BACTERIA & pH

Moro G, Minoli I, Mosca M, Jelinek J, Stahl B, Boehm G. J Pediatr Gastroenterol Nutr 2002; 34:291-295

-1.5

-1.0

-0.5

0

+0.5

+1.0

+1.5

Ch

ange

in s

too

l pH

day

28

vs.

day

0(m

ean

s

SD)

*

*#

0.8g/100ml

(n=27)

0g/100ml(n=33)

0.4g/100ml(n=30)

reference range (IQR) ofbreastfed infants (n=15)

* p<0.01 vs. 0.0, # vs. 0.4 according to ANOVA and Fisher post-hoc-test

Bifidus Change in stool pH

• Safe, Food-Grade Source

• Approved as Food or Food Ingredient

• Exact Characterization

• Chemical and Physical Properties

(No Negative Effect Like: Complexing of Minerals, Vitamins and Fats)

• Physiologic Parameters Like: Digestibility, Taste &Texture

• Clinical Evidence for Prebiotic Effect

CRITERIA FOR THE SELECTION OF PREBIOTICS

After: Boehm G, Fanaro S, Jelinek J, Stahl B, Marini A Acta Paediatr Suppl. 2003 Sep;91(441): 64-7.

Prebiotic concept for infant nutrition..

EFFECTS ON STOOL CHARACTERISTICS

Scholtens, PAMJ, Goossens DAM, Staiano A

World J Gastroenterol. 2014 Oct 7; 20(37):

13446–13452.

http://www.ilsi.org/Europe/Pages/TF_Prebiotics.aspx

FREE ACCESS

Review on Prebiotics by

ILSI-Europe Task Force

Prebiotic Effect: Established Scientific Fact

GRAS Notice (GRN) No.477

http://www.fda.gov/Food/IngredientsPackagingLabeling/

GRAS/NoticeInventory/default.htm

COMMISSION DIRECTIVE 2006/141/EC 2006 on infant formulae and

follow-on formulae and amending Directive 1999/21/EC

…the WAO guideline panel suggests using prebiotic

supplementation in not-exclusively breastfed

infants ….

SYSTEMATIC REVIEW 2016:

PREBIOTICS ON ALLERGY PREVENTION

Potential Mechanisms for Immune

Fitness by unique oligosaccharides

Vos AP, M’rabet L, Stahl B, Boehm G, Garssen J.

Critical Reviews. Immunology 2007

Prebiotic

Effects

Direct

Effects

Immune Fitness

microbes TLRs

Oligos.

SCFA

Galectins

DC-sign

Treg

IL-10TGF-b

+/-

+

+

+

_

Th1 , Th2 , Th1/Th2

Th1

Th2 (type I allergy)

Th2

Th2

Th1

Th1 ?

Th1

Th1

Th1 , Th2

HIV

COPD

Allergies

Asthma

Atopic eczema

Coeliac disease

Cystic Fibroses

Cancer

Elderly

Infants

i

n

f

l

a

m

m

a

t

i

o

n

Autoimmunities Th1 , Th2

Immune dysregulation and NCDs

A model for NCDs?

0

0,05

0,1

0,15

0,2

0,25

0,3

0,35

0,4

0,45

HIV asymptomatic persons Healthy persons

% o

f to

tal b

ac

teri

al lo

ad

(g

eo

me

tric

me

an

)

HIV asymptomatic Healthy

Lac

tob

ac

illi (

%)

0

0,5

1

1,5

2

2,5

3

3,5

4

4,5

5

HIV asymptomatic persons Healthy persons

% o

f to

tal b

ac

teri

al lo

ad

(g

eo

me

tric

me

an

)

HIV asymptomatic Healthy

Bif

ido

bac

teri

a (

%)

HIV asymptomatic Healthy Healthy

Ca

nd

ida

alb

ican

s

(ce

lls

/g w

et

we

igh

t fe

ac

es

)

1.00E+03

1.00E+04

1.00E+05

1.00E+06

1.00E+07

HIV asymptomatic

Ps

eu

do

mo

na

s (

%)

Gori A et al. J Clin Med (2008); Mucosal Immunology (2011)

Altered gut microbiota in HIV infected individuals

COPA trial ,Gori A et al (2011) Mucosal immunology

Expressed as median (range)

15g/d 30g/d

Expressed as mean ± se

15g/d 30g/d

Prebiotic Oligo’s improve the Gut Microbiota of HIV infected Adults

Changes from baseline in activated CD4+ T cells (% CD4+CD25+) during the 52-week

intervention period in the intention-to-treat population from a BITE pilot study (*P = .036,

change from baseline).

Cahn P et al. Clin Infect Dis. 2014;57:139-146

Th1 , Th2 , Th1/Th2

Th1

Th2 (type I allergy)

Th2

Th2

Th1

Th1 ?

Th1

Th1

Th1 , Th2

HIV

COPD

Allergies

Asthma

Atopic eczema

Coeliac disease

Cystic Fibroses

Cancer

Elderly

Infants

i

n

f

l

a

m

m

a

t

i

o

n

Autoimmunities Th1 , Th2

Immune dysregulation and NCDs

Arslanoglu S, Moro GE, Boehm G. J. Nutr.

2007 137(11): 2420-4

Protection Against Allergy-prevention

Atopic Dermatitis (infants at risk)

After 6 months

scGOS/lcFOS

(n=102)

Control

(n=104)

Cu

mu

l. i

nc

ide

nc

e o

f a

top

ic d

erm

ati

tis

10

15

25

30

0

5

20

9.8%

*

9.8%

23.1%

P=0.014 (Fisher test)

scGOS/lcFOS

(n=66)

Control

(n=68)

0

5

10

15

20

25

30

35

27.9%

13.6%

P<0.05(Fisher test)

*

Cu

mu

l. i

nc

ide

nc

e o

f a

top

ic d

erm

ati

tis

After 24 months

Arslanoglu S, Moro GE, Schmitt J, Boehm G.,

J. Nutr. 2008; 138: 1091–1095.

Significant decrease in biomarkers for allergy (serum IgE,

IgG1 and CMA IgG1 in High-Risk Infants at 6 Months)

**p=0.008

Tota l IgE

Placebo Gos/lcFos

1

10

100

1000

IgE

(kU

/l)

Hoffen et al., 2009 Allergy

P<0.0105

Placebo GOS/lcFOS

0.1

1

10

100

1000

IgG

1 (

AU

/ml)

P<0.0105

Total IgG1

(first preliminary indications for tolerance induction-IgG4/Treg)

IgE

IgG

Plasma cells Mast cell

Allergic response

Allergen challenge:

cross-linking surface-

bound Ig

Anti-histamines

Leukotriene

antagonists

NSAID’s

Corticosteroids

Anti-cytokines

Fcε

RI

FcγRI/I

II

Redegeld et al., Curr. Opin. Invest. Drugs, 2009

Redegeld et al., Nature Med 2002

Schouten et al. JACI 2010

IgLC

Inflammation response

atopic dermatitis: higher

levels of Ig-FLC in serum

Schouten et al. JACI 2010, PAI 2011

oligosaccharides down-

regulates Ig-FLC in infants at

risk for allergy

Early dietary intervention with a mixture of prebiotic

oligosaccharides reduce the incidence of allergic

manifestations during the first 2 years of life

Arslanoglu et al., 2008, J. of Nutr. 138:1091-1095

Pre

se

nc

e o

f a

ny a

lle

rgy-r

ela

ted

sym

pto

m

scGOS/lcFOS (n=40) Control (n=49)0

5

10

15

20

25

30

Cu

mu

lati

ve

in

cid

en

ce

of

all

erg

yAtopic Dermatitis Recurrent Wheezing Allergic Rhinitis

0

5

10

15

20scGOS/lcFOS

Control

Protection Against Allergy

5 year follow-up

Arslanoglu S, et al 2011

10

%

26.5

%

3.3%

12.3

%

6.7%

12.2

%

3.3%

16.3

%P < 0.05

P < 0.05 P < 0.05

Oligosaccharides reduce incidence of

Atopic Dermatitis in infants not at risk

(prevention)

Gruber et al. JACI 2010

p<0.0469

8 16 24 520

2

4

6

8

10Placebo

scGOS/lcFOS/AOS

Breastfed

Age (weeks)

Cu

mu

lati

ve i

ncid

en

ce

of

ato

pic

derm

ati

tis

The PATCH study-prevention

Study formula was provided from the moment the mother decided to stop or

supplement breastfeeding. Part of the original study population (38%) was

followed up until 3-5 years of age.

PATCH (12 – 18 months) PATCH FU (3-5 years)

Boyle, Tang et al. Allergy 2016

18 month eczema development 5 year allergic manifestations in

subgroup not weaned <18 weeks

Manuscript in preparationBoyle, Tang et al. Allergy 2016

Beneficial effect of HP + prebiotics related to the timing of

introduction of weaning foods and long-term allergy

development.

Indication of immune-modulatory capacities

of HP + prebiotics

long-term reduction of

sensitization marker

Boyle, Tang et al. Allergy 2016, manuscript in preparation

Biomarkers for “immune tolerance-

immune fitness” upregulated

Boyle, Tang et al. Allergy 2016

A PRO-biotic is a live microorganism

which when administered in adequate

amounts confer a health benefit on the

host (WHO/FAO 2002)

Examples:

Lactobacillus

Bifidobacterium

...

0

100

200

300

400

500

Sham-sens PBS B.animalis B. breve B. infantis L. rhamnosus L. plantarum

Tota

l num

be

r of

cells

in B

ALF

(x 1

04) Lymphocytes

MacrophagesNeutrophils

Eosinophils

B.animalis

Hougee et al. Int. Arch. Allergy Immunol., 2010; Hoffen van et al. Int Arch Allergy Immunol., 2010

.

Probiotics: strain selection is essential!!

(new concepts for allergic inflammation)

* *

?

A synbiotics is the combination of both pro- and prebiotics

Example:

Galacto-Oligosaccharides

Fructo-Oligosaccharides

B breve M16V

Fructo-Oligosaccharides

B breve M16V

Synbiotics prevent acute response for cow’s

milk allergy in vivo (preclinical studies)

Synbiotics reduce acute allergic reaction

Schouten et al. J Nutr 2009

de Kivit et al. Allergy 2012

Synbiotic effect correlated with increased galectin-9

p<0.01

p=0.033

Van de Pol et al, Allergy, 2011

Non-digestible oligosaccharides + B breve M16V reduce

Asthma Markers in Adults (treatment)

Van de Aa et al, Clin Exp All, 2010

Non-digestible oligosaccharides + B breve M16 V reduce

atopic dermatitis in children (treatment)

Synbiotics increase serum galectin-9 in infants

with atopic dermatitis (van der Aa study)

Baseline Week 12 (V4)

de Kivit et al. Allergy 2012

Noisy breathing apart from colds Frequent wheezing

p= 0.001p= 0.04

Lower Prevalence of Asthma like Symptoms in the Synbiotic group

at 1 year Follow Up

Van de Aa et al, Allergy, 2011

Less asthma medication

Non-digestible oligosaccharides + B breve M16V reduce

respiratory symptoms in children (sec. prevention)

Allergy

Obesity

Coronary Heart Disease

Diabetes

Autoimmunity

NCDs

Birth +48 months

Programming

Imprinting

Dietary intervention Prebiotics

Healthy Life

-9 months

PREVENTION of NCDs

Early life: Setting the Right Course for Later Life

Health

Disease

Role in metabolic disorders/diabetes/syndrome X/ obesity: immunometabolism

Role in cachexia/sarcopenia

Role in neurological disorders: Autism, Alzheimer, Depression, Hyperactivity Syndrome, ...

Utrecht University

Hyper immune- responsiveness:

Allergy

Autoimmunity

Chronic inflammatory diseases

Hypo immune- responsiveness:

Infections

Tumors/metastasis

Immune disorders and NCDs

Inflammation

Global Health-WUN

Dietary intervention for the management of NCDs?

Creating a healthy balance!

IMMUNE FITNESS

FIT FOR LIFE

1. Microbiome management (Pro-, Pre-, Syn-, Post-

biotics)

2. Epitopes

3. Antigens/Allergens

4. lcPUFAs

5. Exosomes/lipid vesicles

6. Amino-acids

7. Enzymes

8. Peptides

9. …

New nutritional concepts for allergy

management

1. Selective prebiotics inhibit the onset and severity of

allergy related disorders early and later in life.

PROGRAMMING.

2. Specific prebiotics induce immune biomarkers for

immune fitness and tolerance.

3. Underlying mechanisms indicate a role for gut

integrity, microbiome diversity, immune tolerance,

Tregs, and galectin 9

MAJOR CONCLUSIONS

Immune modulatory mechanisms,

allergy, inflammation, obesity,

autoimmunity, infections, NCDs, …

Grants& industry

Ongoing collaborations

CFACenter food

allergy

Ministery

VWA

UU focus grant

(neuro-mmune)

Acknowledgements/Conflicts of interest

PYRAMID OF EVIDENCE