291-OR: Exercise Modulates Glucose Metabolism in Part through Changes in the Gut Microbiome

Abstract

Exercise is one of the most prescribed interventions in the treatment/prevention of diabetes and metabolic disease. It is well established that different diets affect the distribution of gut microbiota. It has recently been shown that exercise may also modify the gut microbome and these modifications may differ depending on the obesity status of the individual. In this work we investigated whether metabolic changes triggered by exercise are transferable via cecum microbiota transplantationand how this would impact on the obesity response to high fat diet (HFD). Ten-week old, B6J male mice, on chow diet, were reared under either standard sedentary conditions or with access to a running wheel for 4 weeks. Under these conditions the latter mice ran an average of 6 Km per day. Mice were scarified, fecal DNA were sequenced and the cecum microbiota were transplanted into germ-free mice in the presence/absence of HFD. As expected, exercise improved insulin sensitivity and glucose tolerance in the donor mice. Shotgun metagenomic analysis of gut microbiota revealed that exercise was associated with decreased relative abundance of Parasutterella_excrementihominis and Bacteroides_thetaiotaomicron and increased Clostridium clostridioforme CAG:511 and Lactobacillus murinus ASF361. Functional composition of the bacterial metagenome indicated these changes resulted in an upregulation of microbial pathways of valine and methionine metabolism. More importantly, transplant of cecum microbiota from exercised donors to non-exercise donors improved running capacity in lean mice and improved glucose tolerance in mice on HFD. In both groups, this was associated with increased glucose uptake in skeletal muscle soleus and BAT. In summary, exercise reshapes the gut microbiome to improve whole body glucose metabolism, and this effect can be transferred by microbiome transplant. This provides an new opportunity in the treatment of obesity-related insulin resistance. Disclosure B. Brandao: None. M.E. Li: None. W. Cai: None. T.M. Batista: None. M.F. Hirshman: Stock/Shareholder; Self; Abbott Laboratories, AbbVie Inc., Amgen Inc., Colgate-Palmolive Company, Medtronic. L.J. Goodyear: None. C. Kahn: Advisory Panel; Self; MedImmune. Board Member; Self; Kaleido Biosciences. Consultant; Self; AntriaBio, Inc., Cobalt Therapeutics, Flagship Pioneering. Research Support; Self; Alnylam. Funding National Institute of Diabetes and Digestive and Kidney Diseases