Exercise Training Modulates Gut Microbiota Profile and Improves Endotoxemia

Abstract

<h4>INRTRODUCTION:</h4><p>Intestinal metabolism and microbiota profiles are impaired in obesity and insulin resistance. Moreover, dysbiotic gut microbiota has been suggested to promote systemic low-grade inflammation and insulin resistance through the release of endotoxins particularly lipopolysaccharides. We have previously shown that exercise training improves intestinal metabolism in healthy men. To understand whether changes in intestinal metabolism interact with gut microbiota and its release of inflammatory markers, we studied the effects of sprint interval (SIT) and moderate intensity continuous training (MICT) on intestinal metabolism and microbiota in insulin resistance.</p><h4>METHODS:</h4><p>Twenty-six, sedentary subjects (prediabetic n=9, T2D n=17; age 49[SD 4] years; BMI 30.5[SD 3]) were randomized into SIT or MICT. Intestinal insulin-stimulated glucose uptake (GU) and fatty acid uptake (FAU) from circulation were measured using PET. Gut microbiota composition was analysed by 16S rRNA gene sequencing and serum inflammatory markers with multiplex assays and enzyme-linked immunoassay kit.</p><h4>RESULTS:</h4><p>VO2peak improved only after SIT (p=0.01). Both training modes reduced systematic and intestinal inflammatory markers (TNF α, LBP) (time p<0.05). Training modified microbiota profile by increasing Bacteroidetes phylum (time p=0.03) and decreasing Firmicutes/Bacteroidetes ratio (time p=0.04). Moreover, there was a decrease in Clostridium genus (time p=0.04) and Blautia (time p=0.051). Only MICT decreased jejunal FAU (p=0.02). Training had no significant effect on intestinal GU. Colonic GU associated positively with Bacteroidetes and inversely with Firmicutes phylum, ratio Firmicutes/Bacteroidetes and Blautia genus.</p><h4>CONCLUSION:</h4><p>Intestinal substrate uptake associates with gut microbiota composition and activity and whole-body insulin sensitivity. Exercise training improves gut microbiota profiles and reduces endotoxemia.</p>