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From Nutrigenomics to Systems Nutrition - The role of nutrition in metabolic plasticity and health
From Nutrigenomics to Systems Nutrition
The role of nutrition in metabolic plasticity and health
Norwich Medical School & Food and Health Alliance, Norwich Research Park
• No advisory functions for the food industry
• No competitive grants from food or drug
• Not writing diet books
• Not selling ‘snake oil’ or easy solutions
• Twitter: @nutrigenomics
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)
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 (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.
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
We need an ‘independent’ “Nutritional
Science 2.0” or “Next-Generation Nutrition”.
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”
between feast en famine
in energy abundance
Our “paleolithic” genes + modern diets
“Unsafe” foods = Many challenges “Safe” foods = Less challenges
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-
• Plant food components (e.g. bitter, “toxic”: = “healthy”)
– Fibers or secondary plant metabolites (e.g. resveratrol,
• Less foods/calories (caloric restriction)
– “Chromatin exercise”
– “Cell exercise” (e.g. via autophagy)
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
Understanding Nutrition: Identifying the mechanisms involved in the
regulation of chromatin activity and gene transcription
& health of organs
& influencing the
How we can use our genomes more optimally with healthy nutrition & lifestyles
Nutrigenomics & molecular nutrition allow us
to define the mechanistic framework of nutrition
Omics based quantitative analysis of the
nutrition-related genotype-phenotype relationship
‘‘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
Rene Dubos, 1965
Optimized ability of an individual
to adapt to immuno-metabolic
“A state of complete physical,
mental and social well-being and
not merely the absence of disease
or infirmity.” WHO 1948
“Health as the ability to adapt
and to self manage”
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
The intestine – a long organ with great capacity
• Human 6-7 m
• Mouse 35 cm
• Pig 15 m
• Human 2 m
• Mouse 14 cm
• Pig 5 m
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 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
• 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).
The role of the gut
Stem cells &
FAHA: Food and Immuno-Metabolic Health Alliance
Synthesis of short
chain fatty acids
and regulation of
immunity by SCFAs
Role of dietary fibers on gut function
INULIN, FOS, GuarGum, NAXUS (Arabinoxylan), Resistant Starch, Ctrl (Starch)
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
Turnbaugh et al Nature 2013
Animal-based diets decreases diversity
Faecal concentration of SCFAs from
carbohydrate (a) and amino acid (b)
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 oligosaccharides,
disaccharides, monosaccharides, and polyols (FODMAPS)!!!
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, 538–539
More resilience Less resilience
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 biological obstacles
long analysis times,
evolving definitions of
missing standards of
lack of well-defined
physiological ranges, and
missing evidence for
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
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
Optimal health is personal (because of individual (epi)genomes, microbiomes and organ
capacities) => important role for health professionals (GP or dieticians) for personaized
Be not innocent, there are no miracles: You are what you eat, have eaten, host & how