Basic structure of hair and hair growth cycle.pptx
From Nutrigenomics to Systems Nutrition - The role of nutrition in metabolic plasticity and health
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. 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. 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. Most of our genomes
are not that perfect
‘Spit for health’
6. Cell 2014 157, 241-253DOI: (10.1016/j.cell.2014.02.012)
Know your limits & set your ‘healthy boundaries’
8. 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.
9. 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
11. Do not expect magic bullets
or easy solutions for complex problems
12. Do not expect magic bullets
or easy solutions for complex problems
13. “You are what you eat, have eaten & host”
Norway
UK Ecuador
Chad
14. 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
15. 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)
16. 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
17. 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
21. ‘‘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
22. 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
23. 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
25. A simple experiment to study the capacity of the
mouse intestine for dietary fat
26. 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
30. Synthesis of short
chain fatty acids
(SCFAs) by
commensal bacteria
and regulation of
immunity by SCFAs
31. Role of dietary fibers on gut function
SCFA
INULIN, FOS, GuarGum, NAXUS (Arabinoxylan), Resistant Starch, Ctrl (Starch)
microbiota
32. How fiber might keep the gut healthy &
protect against colorectal cancer
33. 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
34. You are what you eat
Foodborne microbes are detectable in the distal gut
36. Factors that contribute to dysbiosis
in irritable bowel syndrome
Reduction in the dietary intake of fermentable oligosaccharides,
disaccharides, monosaccharides, and polyols (FODMAPS)!!!
38. Metabolic plasticity and resilience capacity due to
“genetic richness” is an essential feature of health
Nature 500, 538–539
More resilience Less resilience
40. Not a taboo anymore
The ‘gut’ & ‘faeces’ are ‘bestsellers’
41. 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
42. 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.