Gut microbiota have received attention in the past decade since the discovery of their association with metabolic diseases. Accumulating evidence, mostly from next generation sequencing analysis of obese and lean gut microbiome has helped in understanding their role for development and pathogenesis of diabetes and obesity.
The influence of the gut microbiota in modulating gene expression of intestinal epithelial cells has been recognised to be, in part responsible for effects to overall host metabolism. In particular, for their role in influencing intestinal epithelial cell gene expression, short chain fatty acids (SCFAs) - metabolites produced by specific bacteria following fermentation of foodstuff within the gut - have been investigated for their potential to improve host metabolism in the context of obesity and diabetes. Recent demonstration that butyrate production by specific bacteria in the gut promotes secretion of the incretin hormone, GLP-1, has been attributed to affording advantageous metabolic effects in the face of high fat feeding in mice (1). Our studies with 2 animal models – 1) a novel multigeneration (50 generations) of undernourished (protein and calories) rats (“Thrifty Jerry”) and 2) high fat fed mice that received a SCFA (or saline) delivering osmotic pump to proximal colon, have helped in identifying a potential molecular mechanisms that regulates the development of insulin resistance and obesity.
Using bioinformatics analysis of our next generation sequencing and metagenome analysis of changes in gut microbiota, with expression of small regulatory RNAs, mRNAs, epigenetic modifications and biochemical measurements of glucose-insulin metabolism, we demonstrate a potential mechanism that underlies development of adiposity and insulin resistance. We present, for the first time, a life-course metagenome as well as intervention analysis in these rodent models of insulin resistance and adiposity, demonstrating the role of gut microbime in development of metabolic disease.
(1) Yadav, Hariom, et al. "Beneficial Metabolic Effects of a Probiotic via Butyrate-induced GLP-1 Hormone Secretion." Journal of Biological Chemistry 288.35 (2013): 25088-25097.