nutrichip - international milk genomics consortium · 2013-09-12 · 8th international symposium...

Federal Department of Economic Affairs FDEA

Agroscope Liebefeld-Posieux Research Station ALP-Haras

NutriChip PD Dr Guy Vergères Functional Nutritional Biology Agroscope, Federal Office of Agriculture Berne, Switzerland 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011

2 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]

Toward a dynamic definition of health

“Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity” WHO (1946)

“Health is the ability to adapt and to self manage” Conference “Is health a state or an ability? Towards a dynamic concept of health” (2009)


Metabolic plasticity and health

Godfrey et al, Trends Endocrinol Metab 2010 21:199


60‘000 Kg

(40’000 pills)

20 Kg

Food – much more than a confoundig factor !

….at the same time, 30-40% of cancers are associated with nutrition

http://www.cornerstorkbabygifts.com/


Nutrigenomics (nutritional systems biology)

Functional genomics - a driving power for human nutrition research

Molecular complexity of nutrients

Holistic analytical technologies (genetics, transcriptomics, proteomics, metabolomics, biostatistics)

Human life cycle

http://www.cornerstorkbabygifts.com/


Milk – a nutrient in constant evolution

Yesterday • 200 million years of evolution of the mammary gland

• 10 thousand years of genetic selection of lactose tolerance induced by the pastoral economy

• 2 centuries of dairy technology

Tomorrow • Bovine milk as a strategic vector for the delivery of

nutrients and bacteria to modulate human health


Postprandial blood cell expression of pro-inflammatory genes after the ingestion of milk by healthy subjects

Metabolic plasticity

Anti-inflammatory characteristics of human milk: how, where, why Buescher, 2001 Adv Exp Med Biol 501: 207

Milk – the promoter of chronic Western diseases Melnik, 2009 Med Hypotheses 72:631

Dairy products consumption is associated with decreased levels of inflammatory markers related to cardiovascular disease in apparently healthy adults: the ATTICA study Panagiotakos et al 2010 J Am Coll Nutr 29:357


Postprandial stress as an indicator of metabolic health ?

NutriChip project


The NutriChip project

G. Vergères (Agroscope), S. Carrara (EPFL), R. Hurrell (ETHZ), J. Ramsden (Cranfield University), K. Laederach (Inselspital, Bern), M. Gijs (EPFL)

NutriChip (microscale)

Digestion, intestinal transport & bioactivation (in vitro)

Digestion Transwell (macroscale)

Developpment of dairy products • Technological transformation • Microbioloigcal transformation Sequencing Agroscope lactic acid bacteria (>10’000 strains)

Biomarkers • Intestinal absorption (nutrikinetics) • Metabolism, inflammation, endotoxinemia • Functional genomics (transcriptomics, proteomics, metabolomics)

Selection and characterization of dairy products

Nutritional studies • Lean and obese subjects

http://www.google.ch/imgres?imgurl=http://taikajuoma.ath.cx/bat/milk.jpg&imgrefurl=http://taikajuoma.ath.cx/bat/&usg=__IYFZPSC5ppfvNbL4qIjklfsxGAI=&h=341&w=352&sz=21&hl=de&start=1&zoom=1&tbnid=q7Uilh9tmGoPJM:&tbnh=116&tbnw=120&ei=XqeSToqHNK7E4gSZ5YixAQ&prev=/search?q=milk&um=1&hl=de&sa=N&tbm=isch&um=1&itbs=1







Developpment of dairy products • Technological transformation • Microbioloigcal transformation






Reference meals • Pasteurized whole milk • High-fat meal (60%)

Dairy products • Milk • Cheese • Yogurt

Fat content • Buttermilk • Cream • Skimmed milk

Heat treatment • Raw • Pasteurized • UHT

Species • Cow • Goat • Sheep

Selection of dairy products for screening



Proteomics of specific fractions of dairy products

Cream (MFGM proteins)

lactadherin adipophilin

xanthine oxidase

serum albumin

IGHM

β-lactoglobulin

caseins

lactotransferrin

immunoglobulin receptor

enolase

GAPDH

pyruvate kinase

fructose-bisphosphate aldolase

phosphoglycerate mutase

Yogurt (bacterial proteins)


Protein Atlas for dairy products


Schematic representation of the in vitro digestion

milk

Analysis of macronutrients

saliva pH 6.8

gastric juice pH 2-3

pancreatic juice + bile pH 6.5-7



Release of free fatty acids after in vitro digestion of milk

90% of milk fat is digested to free fatty acids


In vitro digestion of proteins in milk


Peptide length distribution during in vitro digestion of milk

Saliva Gastric juice Pancreatic juice Pancreatic juice w/o bile

Analysis: LC-MS/MS


Peptide length distribution after in vitro digestion of milk

Analysis: Edman degradation


Release of amino acids during in vitro digestion of milk


Release of essential amino acids after in vitro digestion of milk

Bovine milk, an efficient source of essential amino acids for the human digestive system

AA composition of milk AA released by the digestion of milk


Identification of peptides resistant to digestion in dairy products

Clinical indications: inflammation, allergy, hypertension


Applying digested milk onto the intestinal barrier

Lucifer yellow permeability (n=3)

Transepithelial electric resistance (n=3)


Endotoxin – a killer in our gut


Intestinal cells

Immune cells (macrophages)

Inflammation

Intestinal protection against environmental pro-inflammatory molecules


Intestinal cells

Immune cells (macrophages)

Inflammation

In vitro testing of the anti-inflammatory properties of digested dairy products


Selection of inflammatory markers secreted by immune cells based on TLR and cytokine signaling

TLR4 (mRNA)

IL-1b

IL-6


The NutriChip – combining polymer science and microfluidics


The NutriChip – combining sensor nanotechnologies to terabyte image analysis of cellular inflammatory biomarkers


Human postprandial study with high-fat (pro-inflammatory) meal

•Metabolic markers (glucose, triglycerides, insulin, lipoproteins) •Inflammatory markers (IL6, TNFα, IL1β, IL8, IL10, CRP) •Biomarker discovery (serum metabolomics, blood cell transcriptomics & proteomics)


Postprandial dose-response of humans to the high-fat meal


Human postprandial study with selected dairy product

•Metabolic markers (glucose, triglycerides, insulin, lipoproteins) •Inflammatory markers (IL6, TNFα, IL1β, IL8, IL10, CRP) •Biomarker discovery (serum metabolomics, blood cell transcriptomics & proteomics)


microRNA as a new immune-regulatory agent in milk

Breast milk miRNAs-mediated immune development

miRNA in human breast milk microvesicles (resistant to RNAses, low pH, freeze-thawing)

Intake of breast milk miRNAs

Kosaka et al, Silence 2010 1:7

Nutrition-mediated trans-kingdom transfer of bovine milk microRNA to adult humans ?


Additional applications - the Ca-NutriChip


The NutriChip network

ETHZ, Zürich R. Hurrell (Co-PI)

Agroscope, Berne G. Vergères (Co-PI) Inselspital, Berne B. Bogicevic K. Laederach L. Egger C. Buri D. Gille P. Brandt K. Kopf-Bolanz R. Portmann M. Chollet L. Corbino-Giunta F. Schwander P. Silacci B. Walther

EPFL, Lausanne M. Gijs (PI) Q. Ramadan H. Jafarpoorchekab C. Ruffert EPFL, Lausanne S. Carrara (Co-PI) J. Ghaye G. Köklü

Collegium Basilea, Basel J. Ramsden (Co-PI)

http://www.microsens.ch/

http://www.ayanda-biosys.com/index.html

nutrichip - international milk genomics consortium · 2013-09-12 · 8th international symposium...

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