Role of gut microbiota on the exercise-induced metabolic effects in women undergoing bariatric surgery: a translational study

Exercise training exerts additional metabolic effects in bariatric patients despite similar weight and fat loss, which may be at least partially explained by changes in gut microbiota. We aimed to understand the role of gut microbiota on the exercise-induced metabolic effects in women undergoing bariatric surgery by performing a clinical trial and a human-to-mice fecal microbiota transplant (FMT) study. First, 32 women were randomized to either a 6-month exercise training program following RYGB (RYGB + ET) or standard of care (RYGB). A lean control group was assessed once (LEAN). Blood and gut microbiota assessments were performed at baseline and 3 and 9 months after surgery. We next colonized 36 SPF female mice under a high-fat diet with fecal microbiota collected at 9 months, resulting in groups rRGYB, rRGYB+ET and rLEAN. Mice were assessed before and after FMT for gut microbiota and for blood and tissue parameters post FMT only. No between-group differences were observed for body composition and systemic inflammation in bariatric groups. Biochemical parameters improved similarly, but greater improvements in HDL-cholesterol, triglycerides, fasting glucose and fasting insulin were shown in RGYB+ET vs. RGYB. Exercise training increased gut microbiota alpha-diversity and within-group differential abundance analysis showed that it differentially impacted some bacteria genera involved in short-chain fatty acid and endotoxin production. FMT study showed no differences in systemic and adipose tissue inflammation and glucose tolerance, but rRGYB showed higher fasting insulin levels and HOMA-IR when compared with rRGYB+ET and rLEAN. Moreover, all intestinal morphology parameters were worse in RGYB vs. rLEAN, whereas rRGYB+ET showed comparable villi/crypt ratio and histological scores vs. rLEAN. In conclusion, we showed that exercise-training induced changes in gut microbiota were associated with greater improvements in hepatic insulin sensitivity, which may be at least partially explained by more positive changes in intestinal morphology. Our results further underscore the clinical importance of exercise in bariatric patients.