Fecal Microbiota Transfer to Improve Diabetes Control Post-bariatric Surgery

Obesity progresses worldwide with few effective treatments leading to a burst in Bariatric surgery (BS). France is the 3rd country in BS numbers yearly. BS improves diabetes (T2D) and even induces diabetes remission (DR) in 60% of patients. Thus, an expert consensus recommended extending BS to T2D with BMI≥30kg/m² with uncontrolled glycaemia, anticipating even more BS. Glycaemic control further deteriorates in the longer term in non DR (NDR) patients and relapse occurs in some DR patients, urging the need to add new therapy to control glycaemia and provide new recommendations in the future. Obesity and T2D are characterized by gut microbiota dysbiosis with low to very low microbial gene richness (MGR). About 75% of patients' candidates for BS are in the low MGR category. Whereas BS modifies microbiota composition and increases MGR 1-year post-BS, we demonstrated that only a few patients reach high MGR. Dysbiosis can be improved by several means; fibre enriched diet, prebiotics, probiotics also improve metabolic alterations and insulin resistance in mice. However, human studies observed rather divergent results: some studies display a beneficial effect in improving insulin-resistance but to a small extent while others do not display any significant effects at all. Therefore, other innovative strategies should be tested in humans. For example, Faecal microbiota transfer (FMT) ameliorates insulin sensitivity and MGR in metabolic syndrome patients, but was never tested in T2D nor post-BS. Whether adding such an innovative therapy to further modify gut microbiota post-BS can help improve glucose control should be tested. FMT showed health benefits in several diseases (clostridium difficile (CD) and Crohn's). Until recently, FMT was performed using invasive tool (endoscopy or colonoscopy) thus with potential secondary effects, or enema yet maybe less effective. Recent technologic developments enabled to generate oral capsulized FMT (filled with fecal material) performing as well as invasive FMT for CD with good tolerance. This strategy has never been tested in obesity or T2D, whereas in metabolic syndrome patients (before T2D occurrence) and less severe dysbiosis, a proof-of-concept study showed that endoscopic FMT may improve insulin sensitivity after 6 weeks. Yet these studies have included a small number of patients, non T2D and did not test oral FMT. We here hypothesize that an intervention improving dysbiosis after 1-year post-BS might help improve/maintain diabetes control in the long-term. We will examine the effects of FMT (from lean healthy donors) vs. placebo transfer in dietary-controlled non-DR patients after 1-year post-BS, on Hba1c reduction evaluated 6 months' post-intervention