We are what we eat – new insights from nutrigenomics research to understand how diet is shaping our health

Michael MüllerProfessor of Nutrigenomics & Systems Nutrition

Norwich Medical School

@nutrigenomics

28 Oktober Luzern

“You are what you eat”

“You are what you eat, have eaten & host”

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Low-fat meatChickenEggsFish

FruitsVegetables (carrots)NutsHoney

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FruitsVegetablesBeans

MeatChickenFish

GrainMilk/-productsIsolated CarbsIsolated Fat/OilAlcohol

1.200.000 Generations between feast en famine

Paleolithic era

3-4 Generations in energy abundance

Modern Times

Our “paleolithic” ‘hunter-gatherer’ genes + modern diets

Real Foods with ‘challenges’ “Safe, processed” foods = Less challenges

Can we blame our genes?Genes + Nutrition => Phenotype

It is not that easy!

Our genes

• 23 chromosomes

• ≈ 20,000+ genes

Biological Systems Multi-omics for FAHA

Nature Reviews Genetics | AOP, published online 13 January 2015

Phenome

• Metabolic

Syndrome

CVD

NAFLD

• Inflammatory

Diseases

• Prostate

Cancer

Operational +++ +/- + ? +

“We are what we eat, have eaten and what we host”4Rs: Received, Recorded, Remembered & Revealed

Mathers JC (2008) Proc.Nutr.Soc.67,9390-394

You can not change your genes but….You are what you eat, have eaten, host & how you lived

Walter Breuning (1896 – 2011, aged 114 years, 205 days)

(But Breuning was also a lifelong cigar smoker,

but quit in 1999 when he was 103 because it became too expensive)

2 Meals/day,

work as long as

possible &

embrace

challenges

No pain, no gainThe molecular basis of adaptation

No pain – no gainThe powerful effects of exercise (active lifestyle)

Hangelbroek et 2015 submitted

Heatmap of 184 genes that are significantly different between young and old, and are significantly changed by resistance-type exercise

What do we know about the mechanisms?Healthy food (pattern)s have a large impact on our gene expression & phenotype

• (Micro & Macro) Nutrients

– High in Mono & (N-3) polyunsaturated fatty acids

– Sufficient high-quality protein (optimal macro-nutrient ratio)

– Vitamins (e.g. vitamin A & D) , minerals (e.g. Zn)

• Microbiota (from foods)

– Vegetarians / omnivores / carnivores => different microbiota

– “Raw” or fermented food (e.g. diary, cheese) consumption => food-

borne microbiota

– Dietary diversity => microbiota diversity & genetic richness

• Plant food components

– Fibers or secondary plant metabolites (e.g. resveratrol, glucosinolates)

e.g. bitter => “healthy stressors” & impact on microbiota

• Less foods/calories & diet-related stress (caloric restriction)

– “Chromatin exercise” & other epigenetic mechanisms

– “Cell exercise” (e.g. via autophagy)

Understanding NutritionHow nutrients fine-tune the use of our genome potential

Changed

organ

metabolic

capacity

From local problems to systemic diseases –the contribution of the gut

The gut microbiome

• 100,000 billion bacteria

• For each bacteria there are 5-10

viruses

• 10 times more than the number

of cells in the body

• 1,000 different species

• 1 to 2 kg

• 3.3 million genes (150 times

more than the number of genes

in the human genome)

Factors shaping intestinal microbial composition and effects of dysbiosis on host health

Human microbiota: onset and shaping through life stages and perturbations

Strategies For Changing Gut Microbes

• Diets

• Pharmaceuticals / Antimicrobial therapy

– Toxicity, pathogen outgrowth, resistance, expensive

– Vancomycin can be effective for diet-induced obesity

(Murphy et al., Gut, 2012).

• Biotics => Probiotics & Prebiotics

• Microbiota Transplants: FMT

Feed your gut

You are what you eatFeeding different cheeses to mice

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SI1 SI2 SI3

Cheese 1 vs HFD

# d

iffe

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tiall

y e

xp

ressed

gen

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Up

Down

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200

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600

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SI1 SI2 SI3

Cheese 4 vs. HFD

Anti-inflammatory effects of plant food components

What is a healthy diet?"Eat food, not too much, mostly plants"

Michael Pollan, The Omnivore's Dilemma

How the inner tube of life is regulated by our foods

Nutrients

Bioactives

Metabolism

SCFAs

Microbiota

Immune cells

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

Triglyceride/FFA metabolismTransport

12491_at Cd36

26458_at Slc27a2

26569_at Slc27a4

14080_at Fabp1

14079_at Fabp2

Oxidation

omega

13117_at Cyp4a10

11522_at Adh1

26876_at Adh4

11668_at Aldh1a1

beta

11363_at Acadl

11370_at Acadvl

14081_at Acsl1

12894_at Cpt1a

12896_at Cpt2

51798_at Ech1

97212_at Hadha

57279_at Slc25a20

TG/Chylomicron synthesis

110446_at Acat1

238055_at Apob

11813_at Apoc2

13350_at Dgat1

67800_at Dgat2

17777_at Mttp

FA synthesis

104112_at Acly

14104_at Fasn

20249_at Scd1

20250_at Scd2

Transcription regulation

19013_at Ppara

19015_at Ppard

19016_at Pparg

19017_at Ppargc1a

Cholesterol/oxysterol metabolismTransport

11303_at Abca1

27409_at Abcg5

67470_at Abcg8

237636_at Npc1l1

Cholesterol synthesis

74754_at Dhcr24

15357_at Hmgcr

Transcription regulation

22260_at Nr1h2/Lxrb

22259_at Nr1h3/Lxra

20787_at Srebf1

20788_at Srebf2

Bile acid metabolismTransport

16204_at Fabp6

106407_at Osta

330962_at Ostb

20494_at Slc10a2

Transcription regulation

23957_at Nr0b2/Shp

20186_at Nr1h4/Fxr

HF-Chow HF-LF Chow-LF

Bile acids Microb. Metabolism

Drugs Unwanted effects?

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 treatmentsIdentification and personalized treatments of patients at risk for developing type 2 diabetes based on their microbiota

>2017 The Norwich Centre for Food and Health

My take home messages

"Eat food, not too much, mostly plants” …there are no magic bullets

and there are no functional or ‘super’ foods (beside plants…beans,

blueberries, broccoli, oats, soy, spinach, tea, tomatoes, walnuts, or

salmon and maybe fermented foods).

Minimize risks by not chronically over-consuming highly processed

foods.

Embrace challenges from young to old – with foods & lifestyle

(physical activity, exercise).

A healthy gut is an essential gatekeeper for a human health.

Optimal health is personal (because of individual (epi)genomes,

microbiomes and organ capacities) => important role for health

professionals (GPs or dieticians) for personalized advices.

Be not innocent, there are no miracles: You are what you eat, have

eaten, host & how you lived.

Enjoy life…..!!