Moderate-Intensity Exercise Improves Endothelial Function by Altering Gut Microbiome Composition in Rats Fed a High-Fat Diet

Background: Obesity changes gut microbial ecology and is related to endothelial dysfunction. Although the correlation between gut microbial ecology and endothelial dysfunction has been studied in obese persons, the underlying mechanisms by which exercise enhances endothelial function in this group re-main unclear. This study investigated whether exercise improves endothelial function and alters gut mi-crobiome composition in rats fed a high-fat diet (HFD).Methods: Obesity was induced by an HFD for 11 weeks. Whole-body composition and endothelium -dependent relaxation of mesenteric arteries were measured. Blood biochemical tests were performed, and gut microbiomes were characterized by 16S rRNA gene sequencing on an Illumina HiSeq platform.Results: Exercise training for 8 weeks improved body composition in HFD-fed rats. Furthermore, com-pared with the untrained/HFD group, aerobic exercise significantly increased acetylcholine-induced, endothelium-dependent relaxation in mesenteric arteries (P < 0.05) and circulating vascular endothelial growth factor levels (P < 0.01) and decreased circulating C-reactive protein levels (P < 0.05). In addition, exercise and HFD resulted in alterations in the composition of the gut microbiome; exercise reduced the relative abundance of Clostridiales and Romboutsia. Moreover, 12 species of bacteria, including Rombout-sia, were significantly associated with parameters of endothelial function in the overall sample.Conclusions: These results suggest that aerobic exercise enhances endothelial function in HFD-fed rats by altering the composition of the gut microbiota. These findings provide new insights on the applica-tion of physical exercise for improving endothelial function in obese persons.