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We are what we eat – insights from nutrigenomics research to understand how diet is shaping our health
Michael MüllerProfessor of Nutrigenomics & Systems Nutrition
Director of the NRP Food & Health AllianceNorwich Medical School
@nutrigenomics
Outline of my talk
One cannot change the genome but how to use it.The most potent genome challenges: exercise,
fasting/CR, microbiome challenges & “healthy” nutrition.
“Beneficial” commensal bacteria may behave less “beneficial” under the wrong circumstances.
How to use this information for precision treatments or personalized nutrition.
“You are what you eat, have eaten & host”
100
50
0
% EnergyLow-fat meatChickenEggsFish
FruitsVegetables (carrots)NutsHoney
100
50
0
% Energy
FruitsVegetablesBeans
MeatChickenFish
GrainMilk/-productsIsolated CarbsIsolated Fat/OilAlcohol
1.200.000 Generations between feast en famine
Paleolithic era3-4 Generations
in energy abundance
Modern Times
Our “paleolithic” ‘hunter-gatherer’ genes + modern diets
Real Foods with ‘challenges’ “Safe, processed” foods = Less challenges
No pain, no gainThe molecular basis of adaptation
Transcriptional regulatory networks in positive and
negative energy balance – why nutrition matters
Biological systems multi-omics
Nature Reviews Genetics | AOP, published online 13 January 2015
Phenome
• Metabolic SyndromeCVDNAFLD
• Inflammatory Diseases
• ProstateCancer
The most powerful trigger next to exercise is ‘eating less’
Weight Gain Survival
Age (weeks)
Surv
ival
(%)
52 65 78 91 10450
75
100
C
CR
MFINT
**
**
Age (month)
Bod
y weigh
t (g)
15
25
35
45
55
65 CCRMFINT
6 12 24 28
From local problems to systemic diseases – the contribution of the gut
(microbiome)
Feed your gut
1 2 3 4 5 6 7 8 9 10 1 2 3 4 5 6 7 8 9 10 1 2 3 4 5 6 7 8 9 10
AHR activation11622_at AhrDetoxification13076_at Cyp1a114858_at Gsta214859_at Gsta314862_at Gstm118104_at Nqo1Inflammation (ILCs and IELs)19885_at Rorc (ILC)12501_at Cd3e (IEL)12502_at Cd3g (IEL)12525_at Cd8a (IEL)20302_at Ccl3 (IEL)20304_at Ccl5 (IEL)432729_at Tcrg-C (IEL)17067_at Ly6c1 (IEL, type a)16636_at Klra5 (IEL, type b)
12504_at Cd4 (T helper)12475_at Cd14 (Monocytes)12478_at Cd19 (B cells)
HF-Chow HF-LF Chow-LF
Different diets are leading to different gut phenotypes (small intestine)
Dietary impact on the activation of the AhR essential for the gut immune system
3 Diets = 3 functional states
of the gut
What is a healthy diet?"Eat food, not too much, mostly plants"
Michael Pollan, The Omnivore's Dilemma
Anti-inflammatory effects of plant food components
Tilg H, Moschen AR. Food, immunity, and the microbiome Gastroenterology. 2015 May;148(6):1107-19.
Role of dietary fibres on gut function in mice
SCFA
INULIN, FOS, GuarGum, NAXUS (Arabinoxylan), Resistant Starch, Control = Starch
microbiota10 days
Lange K, Hugenholtz F, Jonathan MC, Schols HA, Kleerebezem M, Smidt H, Müller M, Hooiveld GJ. Mol Nutr Food Res. 2015, 59,1590–1602.
Integration of epithelial cell gene expression with luminal microbiota composition
Bacterial groups within Clostridium cluster XIVa positively correlated with genes involved in energy metabolism (1)
Lange K, Hugenholtz F, Jonathan MC, Schols HA, Kleerebezem M, Smidt H, Müller M, Hooiveld GJ. Mol Nutr Food Res. 2015, 59,1590–1602.
PPARg targetsUpstream regulator
Role of Pparg in fibre-dependent gene regulationFibre-specific effects on PPARy transcriptome
Lange K, Hugenholtz F, Jonathan MC, Schols HA, Kleerebezem M, Smidt H, Müller M, Hooiveld GJ. Mol Nutr Food Res. 2015, 59,1590–1602.
Role of gut microbiota in heme induced stress
• Consumption of red meat is associated with increased colorectal cancer risk. We show that the gut microbiota is pivotal in this increased risk.
• Mice receiving a diet with heme, a proxy for red meat, show a damaged gut epithelium and a compensatory hyperproliferation that can lead to colon cancer.
• Mice receiving heme together with antibiotics do not show this damage and hyperproliferation.
Proposed mechanism of how microbiota facilitates heme-induced compensatory hyperproliferation
Noortje Ijssennagger et al. PNAS 2015;112:10038-10043
We are what we fed them…?
‘our gastrointestinal tract is not only the body's most under-appreciated organ, but "the brain's most important adviser”’.
Future Perspective: Stratification and precision treatments
Identification and personalized treatments of patients at risk for developing type 2 diabetes based on their microbiota
http://personalnutrition.org
Summary One cannot change the genome but the use of genome capacity =>
phenotype plasticity is an essential feature of health. The most potent genome challenges: exercise, fasting/CR,
microbiome challenges & “healthy” nutrition. "Eat food, not too much, mostly plants”: many bioactive molecules. Transcription factors (e.g. PPARg, FXR, AHR or NRF2) are involved
in host sensing mechanisms of microbial metabolites & food bioactives.
“Beneficial” commensal bacteria may behave less “beneficial” under the wrong circumstances (e.g. dietary heme or other dietary stressors).
Embrace challenges from young to old – with diverse foods & lifestyles that ‘mildly’ challenge the genome.
Precision treatments of people at risk for developing non-communicable diseases based on genome/phenome data.
>2017 The Norwich Centre for Food and Health