A short-term randomized clinical trial testing feasibility and physiological responses of a Ruminococcus torques strain in healthy overweight humans

Background: The human gut microbiota interacts with host biology as exemplified by the effects of the Ruminococcus torques (RT) ATCC 27756 strain - a commensal human intestinal bacterial strain that synthesizes the polypeptides RORDEP1 and RORDEP2 which in rodents improve metabolism. Aim: Motivated by the metabolic effects of the RT strain in the rodent host, we explored in a short-term double blind and placebo-controlled randomized cross-over trial the feasibility and potential physiological responses of the same bacterial strain in humans. Materials and Methods: The trial included 32 healthy overweight adults. We infused either 3.1×1011 colony forming units of the live RT ATCC 27756 strain or placebo into the duodenum during an observation period of six hours including a two-hour oral glucose tolerance test. Results: The infusion of the bacterium was safe and well-tolerated. We found no effects on the primary endpoint of the trial, insulin sensitivity. Compared to placebo, short-term RT infusion induced a relative rise in plasma concentrations of Glucagon-Like-Peptide-1 (GLP-1) and Peptide YY (PYY) in parallel with a relative decline in Gastric Inhibitory Polypeptide (GIP). These intestinal hormone responses mirrored those previously reported from studies in rats. The abundance of secondary bile acids in plasma as well as a plasma marker of bone remodeling increased after infusion of RT compared to placebo. Measures of glucose tolerance, energy expenditure, cutaneous thermography, and main markers of systemic low-grade inflammation remained unchanged. Conclusion: Duodenal infusion for six hours of the RT ATCC 27756 strain in healthy overweight men shows that the bacterial strain is well tolerated, and the short-term effects on intestinal hormone release align with those previously reported in rodents.