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From Nutrigenomics to Systems Nutrition
The role of nutrition in metabolic plasticity and health
Michael Müller
Norwich Me...
Disclosure
• No advisory functions for the food industry
• No competitive grants from food or drug
companies
• Not writing...
You are what you eat, have eaten, host & how you lived
2 Meals/day, work as long as possible & embrace challenges
Walter B...
Most of our genomes
are not that perfect
‘Spit for health’
Cell 2014 157, 241-253DOI: (10.1016/j.cell.2014.02.012)
Know your limits & set your ‘healthy boundaries’
Back to reality
The Challenge of Non-Communicable Diseases
2014 – our health research reality
The next health tsunami => non-communicable diseases (NCDs) >
communicable diseases (CD...
Nutrition & Health Sciences 2014
State of the art?
 Widely recognized that diet is one of the
most important environmenta...
We are susceptible to
QUAKERY & SNAKE OIL sellers
Do not expect magic bullets
or easy solutions for complex problems
Do not expect magic bullets
or easy solutions for complex problems
“You are what you eat, have eaten & host”
Norway
UK Ecuador
Chad
100
50
0
% Energy
Low-fat meat
Chicken
Eggs
Fish
Fruits
Vegetables (carrots)
Nuts
Honey
100
50
0
% Energy
Fruits
Vegetable...
Your are what you eat & host
Healthy food (pattern)s have a large impact on our gene expression & phenotype
• (Micro & Mac...
Ronald M. Evans , David J. Mangelsdorf Nuclear Receptors, RXR, and the Big Bang Cell, Volume 157, Issue 1, 2014, 255 - 266...
Understanding Nutrition: Identifying the mechanisms involved in the
regulation of chromatin activity and gene transcriptio...
Blood
triglycerides
Nutrigenomics & molecular nutrition allow us
to define the mechanistic framework of nutrition
Omics based quantitative analysis of the
nutrition-related genotype-phenotype relationship
Phenotype
Microbiome
Metabolome...
The molecular basis of adaptation
‘‘The states of health or disease are
the expressions of the success or
failure experienced by the organism
in its efforts...
de Wit NJ, Afman LA, Mensink M, Müller M
Phenotyping the effect of diet on non-alcoholic
fatty liver disease J Hepatol 201...
The intestine – a long organ with great capacity
Small intestines:
• Human 6-7 m
• Mouse 35 cm
• Pig 15 m
Large intestines...
Health and disease
Changes in gut microbiota composition and metabolism
A simple experiment to study the capacity of the
mouse intestine for dietary fat
We should not chronically overload our organs
• Saturated fat (but not unsaturated fat) stimulates obesity and fatty liver...
Plant Foods
(JIC/IFR/UEA)
Human Nutrition
(UEA/IFR/NNUH)
Molecular
Nutrition
(UEA/IFR/JIC)
Gut-Food-
Microbe
Interaction
(...
The power of
plant foods
A comprehensive multi-Omics based approach to
investigate the dynamic food-host-microbe interaction
4 5 6 7 8 9 10 1 2 3 4...
Synthesis of short
chain fatty acids
(SCFAs) by
commensal bacteria
and regulation of
immunity by SCFAs
Role of dietary fibers on gut function
SCFA
INULIN, FOS, GuarGum, NAXUS (Arabinoxylan), Resistant Starch, Ctrl (Starch)
mi...
How fiber might keep the gut healthy &
protect against colorectal cancer
The gut microbiome can rapidly respond to altered diet, potentially
facilitating the diversity of human dietary lifestyles...
You are what you eat
Foodborne microbes are detectable in the distal gut
Interactions among host, microbiota, and metabolites
Factors that contribute to dysbiosis
in irritable bowel syndrome
Reduction in the dietary intake of fermentable oligosacch...
Factors shaping intestinal microbial composition
and effects of dysbiosis on host health
Metabolic plasticity and resilience capacity due to
“genetic richness” is an essential feature of health
Nature 500, 538–5...
The lifelong importance of our microbiome
for our personal health (boundaries)
Not a taboo anymore
The ‘gut’ & ‘faeces’ are ‘bestsellers’
Ready for prime time?
Introduction of metagenomic tools into clinical practice
is facing major technical as well as biolog...
Take home messages
A systems nutrition approach (not correlation science) is essential to understand causal
relationships ...
From  Nutrigenomics to Systems Nutrition - The role of nutrition in metabolic plasticity and health
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From  Nutrigenomics to Systems Nutrition - The role of nutrition in metabolic plasticity and health

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Conference Voeding leeft 23 mei 2014 M Muller

Published in: Health & Medicine, Technology

From  Nutrigenomics to Systems Nutrition - The role of nutrition in metabolic plasticity and health

  1. 1. From Nutrigenomics to Systems Nutrition The role of nutrition in metabolic plasticity and health Michael Müller Norwich Medical School & Food and Health Alliance, Norwich Research Park @nutrigenomics
  2. 2. Disclosure • No advisory functions for the food industry • No competitive grants from food or drug companies • Not writing diet books • Not selling ‘snake oil’ or easy solutions • Twitter: @nutrigenomics
  3. 3. You are what you eat, have eaten, host & how you lived 2 Meals/day, work as long as possible & embrace challenges 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)
  4. 4. Most of our genomes are not that perfect ‘Spit for health’
  5. 5. Cell 2014 157, 241-253DOI: (10.1016/j.cell.2014.02.012) Know your limits & set your ‘healthy boundaries’
  6. 6. Back to reality The Challenge of Non-Communicable Diseases
  7. 7. 2014 – our health research reality The next health tsunami => non-communicable diseases (NCDs) > communicable diseases (CDs) Our research often still focused on treatment instead of prevention of NCDs. Nutrition and food-related research often related to the needs of the food industry (e.g. EFSA health claims). Research largely fragmented with the ambition to find “magic bullets” (‘gene X is responsible for the disease & could be a drug target’). No efficient strategies to treat or cure complex NCDs (Diabetes, CVD, cancer, mental disorders). Mono-target approaches (“one drug fits all”) fail in the efficient treatment of NCD => increasing health care costs & decreasing quality of life. A “creative deconstruction of medicine” (Eric Topol) and of the related research is needed.
  8. 8. Nutrition & Health Sciences 2014 State of the art?  Widely recognized that diet is one of the most important environmental factors that influence phenotype plasticity and health.  Nutritional science is often still correlation science focusing on public health but less on personal health.  ‘Nutrition’ has 7,235,000,000 n=1 believers & several diet “gurus” with their followers.  Food production was & is largely family business but a few multinationals (industry & supermarkets) are changing this and there are huge economical interests (‘big money’).  What is needed is not enough calories for all but enough nutrition (real foods) for all (9 Billion).  We need an ‘independent’ “Nutritional Science 2.0” or “Next-Generation Nutrition”. 1883
  9. 9. We are susceptible to QUAKERY & SNAKE OIL sellers
  10. 10. Do not expect magic bullets or easy solutions for complex problems
  11. 11. Do not expect magic bullets or easy solutions for complex problems
  12. 12. “You are what you eat, have eaten & host” Norway UK Ecuador Chad
  13. 13. 100 50 0 % Energy Low-fat meat Chicken Eggs Fish Fruits Vegetables (carrots) Nuts Honey 100 50 0 % Energy Fruits Vegetables Beans Meat Chicken Fish Grain Milk/-products Isolated Carbs Isolated Fat/Oil Alcohol 1.200.000 Generations between feast en famine Paleolithic era 3-4 Generations in energy abundance Modern Times Our “paleolithic” genes + modern diets “Unsafe” foods = Many challenges “Safe” foods = Less challenges
  14. 14. Your are what you eat & host Healthy food (pattern)s have a large impact on our gene expression & phenotype • (Micro & Macro) Nutrients – Mono & polyunsaturated fatty acids – Sufficient high-quality protein (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 • Plant food components (e.g. bitter, “toxic”: = “healthy”) – Fibers or secondary plant metabolites (e.g. resveratrol, glucosinolates,....) • Less foods/calories (caloric restriction) – “Chromatin exercise” – “Cell exercise” (e.g. via autophagy)
  15. 15. Ronald M. Evans , David J. Mangelsdorf Nuclear Receptors, RXR, and the Big Bang Cell, Volume 157, Issue 1, 2014, 255 - 266 Metabolic homeostasis is regulated by nutrient sensors
  16. 16. Understanding Nutrition: Identifying the mechanisms involved in the regulation of chromatin activity and gene transcription Metabolic capacity & health of organs & influencing the epigenetic memory How we can use our genomes more optimally with healthy nutrition & lifestyles
  17. 17. Blood triglycerides Nutrigenomics & molecular nutrition allow us to define the mechanistic framework of nutrition
  18. 18. Omics based quantitative analysis of the nutrition-related genotype-phenotype relationship Phenotype Microbiome Metabolome Proteome Transcriptome Epigenome Genotype Nutrition Foods Physical activity
  19. 19. The molecular basis of adaptation
  20. 20. ‘‘The states of health or disease are the expressions of the success or failure experienced by the organism in its efforts to respond adaptively to environmental challenges’’ Rene Dubos, 1965 Optimized ability of an individual to adapt to immuno-metabolic challenges (2014) “A state of complete physical, mental and social well-being and not merely the absence of disease or infirmity.” WHO 1948 What is “Health as the ability to adapt and to self manage” BMJ 2011
  21. 21. de Wit NJ, Afman LA, Mensink M, Müller M Phenotyping the effect of diet on non-alcoholic fatty liver disease J Hepatol 2012 . A systems nutrition view of health & disease
  22. 22. The intestine – a long organ with great capacity Small intestines: • Human 6-7 m • Mouse 35 cm • Pig 15 m Large intestines: • Human 2 m • Mouse 14 cm • Pig 5 m
  23. 23. Health and disease Changes in gut microbiota composition and metabolism
  24. 24. A simple experiment to study the capacity of the mouse intestine for dietary fat
  25. 25. We should not chronically overload our organs • Saturated fat (but not unsaturated fat) stimulates obesity and fatty liver disease and affects gut microbiota composition (reduced microbial diversity and increased the Firmicutes-to-Bacteroidetes ratio) by an enhanced overflow of dietary fat to the distal intestine. • Unsaturated fats are more effectively taken up by the small intestine, likely by more efficiently activating nutrient sensing systems and thereby contributing to the prevention the development of early pathologies (e.g. NASH). Food Colon
  26. 26. Plant Foods (JIC/IFR/UEA) Human Nutrition (UEA/IFR/NNUH) Molecular Nutrition (UEA/IFR/JIC) Gut-Food- Microbe Interaction (IFR/UEA) Gut Mucosal Immunity (IFR/UEA) Human Gut (Patho)biology (NNUH/UEA/IFR) The role of the gut for systemic diseases (UEA/NNUH/IFR) Stem cells & organ memory (IFR/UEA) Network analysis & Systems integration (TGAG/UEA/IFR) FAHA: Food and Immuno-Metabolic Health Alliance
  27. 27. The power of plant foods
  28. 28. A comprehensive multi-Omics based approach to investigate the dynamic food-host-microbe interaction 4 5 6 7 8 9 10 1 2 3 4 5 6 7 8 9 10 Ahr Cyp1a1 Gsta2 Gsta3 Gstm1 Nqo1 Rorc (ILC) Cd3e (IEL) Cd3g (IEL) Cd8a (IEL) Ccl3 (IEL) Ccl5 (IEL) Tcrg-C (IEL) Ly6c1 (IEL, type a) Klra5 (IEL, type b) Cd4 (T helper) Cd14 (Monocytes) Cd19 (B cells) HF-LF Chow-LF 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 activation 11622_at Ahr Detoxification 13076_at Cyp1a1 14858_at Gsta2 14859_at Gsta3 14862_at Gstm1 18104_at Nqo1 Inflammation (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
  29. 29. Synthesis of short chain fatty acids (SCFAs) by commensal bacteria and regulation of immunity by SCFAs
  30. 30. Role of dietary fibers on gut function SCFA INULIN, FOS, GuarGum, NAXUS (Arabinoxylan), Resistant Starch, Ctrl (Starch) microbiota
  31. 31. How fiber might keep the gut healthy & protect against colorectal cancer
  32. 32. The gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles Turnbaugh et al Nature 2013 Animal-based diets decreases diversity Faecal concentration of SCFAs from carbohydrate (a) and amino acid (b) fermentation
  33. 33. You are what you eat Foodborne microbes are detectable in the distal gut
  34. 34. Interactions among host, microbiota, and metabolites
  35. 35. Factors that contribute to dysbiosis in irritable bowel syndrome Reduction in the dietary intake of fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPS)!!!
  36. 36. Factors shaping intestinal microbial composition and effects of dysbiosis on host health
  37. 37. Metabolic plasticity and resilience capacity due to “genetic richness” is an essential feature of health Nature 500, 538–539 More resilience Less resilience
  38. 38. The lifelong importance of our microbiome for our personal health (boundaries)
  39. 39. Not a taboo anymore The ‘gut’ & ‘faeces’ are ‘bestsellers’
  40. 40. Ready for prime time? Introduction of metagenomic tools into clinical practice is facing major technical as well as biological obstacles  long analysis times,  evolving definitions of reference microbiota,  missing standards of analysis methods, algorithms, and databases,  lack of well-defined physiological ranges, and  missing evidence for cause–effect relationships. Ingeborg Klymiuk, Christoph Högenauer, Bettina Halwachs, Gerhard G. Thallinger, W. Florian Fricke, Christoph Steininger. A Physicians' Wish List for the Clinical Application of Intestinal Metagenomics 2014 DOI: 10.1371/journal.pmed.1001627
  41. 41. Take home messages A systems nutrition approach (not correlation science) is essential to understand causal relationships between organ and systemic health => next-generation nutritional sciences. A healthy gut is an essential gatekeeper for a human health. 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). "Eat food, not too much, mostly plants”. Diverse food patterns (calories & composition) will keep your body flexible & healthy: “genetic richness” is an essential feature of health. Minimize risks by not chronically over consuming highly processed foods with little nutritional value and diluted protein content, added sugars (FODMAPs) or saturated fats (& drink water). Know your body, your genome capacity and your healthy boundaries in order to stay healthy as long as possible – you can train the resilience capacity by healthy challenges (diet/exercise). Optimal health is personal (because of individual (epi)genomes, microbiomes and organ capacities) => important role for health professionals (GP or dieticians) for personaized advices. Be not innocent, there are no miracles: You are what you eat, have eaten, host & how you lived.

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