Effects of aerobic exercise on inflammation and gut microbiota in obese mice: a metagenomic and metabolomic analysis.

BACKGROUND: Aerobic exercise can ameliorate insulin resistance (IR). However, the mechanism by which aerobic exercise regulates the gut microbiome to ameliorate IR and obesity remains unexplored. METHODS: Obese models were established by feeding C57BL/6 male mice a high-fat diet. A total of 26 mice were randomly divided into control group (group A, N = 8) and high-fat diet group (HFD group, N = 18). Successfully modeled mice were further assigned to model group (group B, N = 8) and exercise group (group C, N = 8). Group C underwent a 6-week treadmill exercise program (12 m/min, 60 min per day, 5 days per week). After intervention, colon tissue morphology was observed through hematoxylin-eosin staining, serum lipids and inflammatory indicators levels were detected by ELISA. The changes in the intestinal microbiota of the mice were also examined using metagenomic sequencing and UPLC-MS non-targeted metabolomics. RESULTS: Compared with the group A, the body weight, TC, TG, LDL-C, blood glucose, insulin, and IR in the group B significantly increased (P < 0.01), while the levels of pro-inflammatory cytokines TXNIP, TNF-α, NLRP3, IL-1β, and IL-18 significantly increased (P < 0.05 or P < 0.01). Compared with the group B, aerobic exercise reduced the body weight, TC, blood glucose, insulin, IR, TXNIP, TNF-α and other indicators in obese mice (P < 0.05 or P < 0.01). Moreover, aerobic exercise can regulate the imbalance of the intestinal flora in obese mice and ameliorate the disorder of metabolites. The metabolic pathways including arachidonic acid metabolism and histidine metabolism showed the most significant differences after the intervention of aerobic exercise. CONCLUSIONS: In conclusion, aerobic exercise can ameliorate glucose and lipid metabolism, IR, inflammatory response, and regulate the intestinal microecology and metabolic disorders in obese mice. The mechanism may be closely related to enhancing the diversity of intestinal flora, regulating the metabolism of arachidonic acid and histidine.