A short-term randomized clinical trial testing feasibility of and physiological responses to 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. 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. METHODS: 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. Insulin sensitivity measured as Matsuda Insulin Sensitivity Index was the primary endpoint. RESULTS: The infusion of the bacterium was safe and well-tolerated. We found no effects on the primary endpoint of the trial. 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. CONCLUSIONS: Duodenal infusion during six hours of the RT ATCC 27756 strain in healthy overweight humans shows that the bacterial strain is well tolerated, and the short-term effects on intestinal hormone release align with those previously reported in rodents. TRIAL REGISTRATION: The trial is registered prospectively in ClinicalTrials.gov on 2022-06-28 with ID NCT05448274 (https://clinicaltrials.gov/study/NCT05448274?intr=ruminococcus%20torques&viewType=Card&rank=1).