Fecal Microbiota Transfer to Improve Diabetes Control Post-bariatric Surgery
Status:
Not yet recruiting
Trial end date:
2029-02-01
Target enrollment:
Participant gender:
Summary
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