NutriChip - International Milk Genomics Consortium · 2013-09-12 · 8th International Symposium...
Transcript of 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)
3 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
Metabolic plasticity and health
Godfrey et al, Trends Endocrinol Metab 2010 21:199
4 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
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
5 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
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
6 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
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
7 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
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
8 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
Postprandial stress as an indicator of metabolic health ?
NutriChip project
9 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
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
10 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
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
Biomarkers • Intestinal absorption (nutrikinetics) • Metabolism, inflammation, endotoxinemia • Functional genomics (transcriptomics, proteomics, metabolomics)
Selection and characterization of dairy products
Nutritional studies • Lean and obese subjects
11 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
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
12 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
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)
13 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
Protein Atlas for dairy products
14 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
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
Biomarkers • Intestinal absorption (nutrikinetics) • Metabolism, inflammation, endotoxinemia • Functional genomics (transcriptomics, proteomics, metabolomics)
Selection and characterization of dairy products
Nutritional studies • Lean and obese subjects
15 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
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
16 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
Release of free fatty acids after in vitro digestion of milk
90% of milk fat is digested to free fatty acids
17 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
In vitro digestion of proteins in milk
18 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
Peptide length distribution during in vitro digestion of milk
Saliva Gastric juice Pancreatic juice Pancreatic juice w/o bile
Analysis: LC-MS/MS
19 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
Peptide length distribution after in vitro digestion of milk
Analysis: Edman degradation
20 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
Release of amino acids during in vitro digestion of milk
21 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
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
22 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
Identification of peptides resistant to digestion in dairy products
Clinical indications: inflammation, allergy, hypertension
23 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
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
Biomarkers • Intestinal absorption (nutrikinetics) • Metabolism, inflammation, endotoxinemia • Functional genomics (transcriptomics, proteomics, metabolomics)
Selection and characterization of dairy products
Nutritional studies • Lean and obese subjects
24 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
Applying digested milk onto the intestinal barrier
Lucifer yellow permeability (n=3)
Transepithelial electric resistance (n=3)
25 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
Endotoxin – a killer in our gut
26 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
Intestinal cells
Immune cells (macrophages)
Inflammation
Intestinal protection against environmental pro-inflammatory molecules
27 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
Intestinal cells
Immune cells (macrophages)
Inflammation
In vitro testing of the anti-inflammatory properties of digested dairy products
28 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
Selection of inflammatory markers secreted by immune cells based on TLR and cytokine signaling
TLR4 (mRNA)
IL-1b
IL-6
29 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
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
Biomarkers • Intestinal absorption (nutrikinetics) • Metabolism, inflammation, endotoxinemia • Functional genomics (transcriptomics, proteomics, metabolomics)
Selection and characterization of dairy products
Nutritional studies • Lean and obese subjects
30 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
The NutriChip – combining polymer science and microfluidics
31 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
The NutriChip – combining sensor nanotechnologies to terabyte image analysis of cellular inflammatory biomarkers
32 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
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
Biomarkers • Intestinal absorption (nutrikinetics) • Metabolism, inflammation, endotoxinemia • Functional genomics (transcriptomics, proteomics, metabolomics)
Selection and characterization of dairy products
Nutritional studies • Lean and obese subjects
33 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
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)
34 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
Postprandial dose-response of humans to the high-fat meal
35 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
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)
36 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
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 ?
37 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
Additional applications - the Ca-NutriChip
38 8th International Symposium Milk Genomics and Human Health Melbourne, Australia 15-17 November 2011, [email protected]
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)