The role of intestinal microbiota on the cardiometabolic response to exercise in women undergoing bariatric surgery: from clinical outcomes to potential mechanisms

Abstract

Bariatric surgery is the treatment of choice for severe obesity leading to short-term improvements in a number of associated comorbidities. However, less pronounced effects are reported in the long-run, suggesting that the sustainability of a number of surgery-induced protective benefits may be transient in the absence of changes in lifestyle. We have recently shown that improvements in endothelial function, insulin sensitivity and systemic inflammation observed 3 months after bariatric surgery returned to baseline values nine months after surgery despite substantial weight and fat loss. Importantly, an exercise training program prevented this effect. Changes in gut microbiota are directly associated with obesity-related metabolic disorders. Bariatric surgery has been shown to impact gut microbiota diversity of obese patients, so that it becomes more similar to that observed in normal-weight individuals. Recent studies also suggest the exercise also increases gut microbiota diversity. Thus, one may speculate that this could explain the protective effects of exercise observed in our patients. Thus, the aim of the present study is to investigate the effects of an exercise training program in gut microbiota and its association with cardiometabolic risk factors in patients undergoing bariatric surgery. This proposal encompasses two studies. Study 1 is a clinical randomized trial, which is part of a larger study aimed at gathering knowledge on the effects of an exercise training program in bariatric surgery patients (NCT02441361). After screening, patients will be randomly allocated into one of the two groups: exercise trained (strength + aerobic training; RGBY + TF) and non-exercise trained (RGBY). All patients will undergo a Roux-en-Y Gastric Bypass (RYGB) surgery. Three months after surgery, subjects of the RGBY+TF group will undergo a 6-month exercise training program. At baseline, 3 (3 MONTHS) and 9 months (9 MONTHS) after surgery, patients will be assessed for body composition, insulin sensitivity, physical capacity, physical activity level, systemic inflammation, endothelial function, gut microbiota diversity, and food intake. A healthy control group will be assessed at baseline only for comparison purposes. Study 2 will be a proof-of-concept experimental trial, in which 40 Swiss mice will receive a high-fat diet for 14 weeks in order to become obese. After this period (14 WK), animals will be randomized into four groups: mRGYB - this group will be transplanted with feces from the RGYB group of Study 1 collected at 9 MONTHS. mRGYB+TF - this group will be transplanted with feces from the RGYB+TF group of Study 1 collected at 9 MONTHS. mCTRL - this group will be transplanted with feces from the CTRL group of Study 1; and mAUT - autologous control group, which will be transplanted with feces from 40 mice collected at 14 WK. Six weeks after the transplant (20 WK), animals will be assessed for insulin sensitivity (glucose and insulin tolerance tests), body composition (DXA), and systemic inflammation. Skeletal muscle will also be collected for lipid oxidation analyses and triacylglycerol, diacylglycerol, and ceramide content, and expression of genes and proteins associated with lipid oxidation and insulin sensitivity. (AU)