Costa rica 2_lecture 8 Oct 2012 "Nutrigenomics of the gut"
Nutrigenomics to explore the impact of the intestine for metabolic homeostasis Michael Müller Netherlands Nutrigenomics Centre & Nutrition, Metabolism and Genomics Group Division of Human Nutrition, Wageningen University @nutrigenomics
Organ and systemic responses to dietary lipids Lipids FFA Remnant VLDL LPL Chylomicrons
A major role for PPARain intestinal fatty acid sensing Physiol Genomics. 2007 ;30(2):192-204
Response to the intestine to different doses of dietary fat De Wit PLOS one 2011
Dose-dependent effects of dietary fat on development of obesity inrelation to intestinal differential gene expression in C57BL/6J mice De Wit PLOS one 2011
Robust & concentration dependent effects in small intestine Differentially regulated intestinal genes by high fat diet C1 C2 C3 C4 C5 C6 C7 C8 C9 C10 De Wit PLOS one 2011
Heat map diagrams of fat-dose dependently regulated genes,categorized according to their biological function De Wit PLOS one 2011
Cellular localization and specific lipid metabolism-related function of fat-dose dependently regulated genes De Wit PLOS one 2011
Conclusion: Do not overload the gut 40 cm4 cmC1 C2 C3 C4 C5 C6 C7 C8 C9 C10 10% FAT 45% FAT
Diet-independent and -dependent microbial effects on host metabolism
Saturated fat affects obesity and gut microbiota composition De Wit et al AJPhysiol 2012
Intake, fecal loss and absorption of total energy and dietary fat De Wit et al AJPhysiol 2012
HF-PO diet reduced microbial diversity andincreased the Firmicutes-to-Bacteroidetes ratio De Wit et al AJPhysiol 2012
Lipid metabolism-related gene expression in the distal small intestine after 8 weeks of diet intervention De Wit et al AJPhysiol 2012
Conclusions• Saturated fat stimulates obesity and hepatic steatosis and affects gut microbiota composition by an enhanced overflow of dietary fat to the distal intestine.
Influence of aging on intestinal functions• Young (4 M) & old (21 M) male C57BL/6 J mice on a control low-fat (10E%) or a high-fat diet (45E%) for 2 weeks.• Small and large intestine were isolated and the small intestine was divided in three equal parts.• Mucosal scrapings from each segment to determine differential gene expression by microarray analysis and global DNA methylation by pyrosequencing.
Conclusions• No significant aging-induced morphological changes in the small intestine or the colon of 21-month-old mice. No decrease in macronutrient metabolic functions of the intestine of old mice.• Micronutrient metabolism might be affected in old mice which might contribute to some of the micronutrient deficiencies frequently occurring in the elderly.• Decrease in global DNA methylation and the altered status of the immune system of the colon might have play a causal role in the decreased health status of this organ at old age.• => Ageing changes metabolic plasticity by epigenetic mechanisms. Structural, functional and molecular analysis of the effects of aging in the small intestine and colon of C57BL/6 J mice BMC Medical Genomics 2012, 5:38
If the gut stays flexible it is staying healthy
Guido HooiveldMark BoekschotenNicole de WitWilma SteegengaNoortje IJssennagger+ many more