Anaerobutyricum soehngenii (previously Eubacterium hallii) is a butyrate-producing next-generation beneficial microbe generally recognized as safe. Several short-term intervention trials by A. soehngenii L2-7 have shown improvement of insulin sensitivity in prediabetic subjects and type 2 diabetes patients. To determine the long-term cardiometabolic benefits and safety, we performed a 3-month double-blind, randomized placebo-controlled intervention in 98 prediabetic insulin-resistant adults in Europe and U.S. with daily administration of encapsulated cells of A. soehngenii CH-106, a tetracycline-sensitive isogenic derivative of strain L2-7. Compared to placebo, A. soehngenii-treated subjects showed significantly reduced glycemic variability (1% reduction in the coefficient of variation; p = 0.01) and improved glycemic control (6% reduction in the overall net glycemic action-1; p < 0.05), including reduced serum glycated hemoglobin (HbA1c) levels when including the 4-week washout period (1 mmol/mol reduction; p < 0.05). Moreover, diastolic blood pressure was significantly reduced in all A. soehngenii-treated subjects (3 mm Hg; p < 0.05). The study product was well-tolerated and had no effect on the global intestinal microbiota composition, including alpha and beta-diversity, besides an increased abundance of A. soehngenii in the treatment group, indicative of compliance. The U.S. participants, compared to those in Europe, responded best, notably in the oral glucose tolerance tests (15% improvement in the area-under-the curve of plasma glucose levels; p = 0.039) or coefficient of variation (reduction of 3.1%; p < 0.05). This potentially relates to a more severe prediabetic state in U.S. subjects, associated with significantly reduced (1.5-3.5-fold) relative abundance of Bifidobacterium, Coprococcus, Ruminococcus spp. and two-fold increased relative abundance of Lachnoclostridium spp. In conclusion, daily oral supplementation with A. soehngenii was safe and improved various markers of glycemic control, reduced HbA1c levels and diastolic blood pressure, indicating a novel microbiome-based approach to improve cardio-metabolic health in adults at risk for developing type 2 diabetes.Clinical trial reg. no. NCT04529473, clinicaltrials.govSocial media summary 120 characters: Anaerobutyricum soehngenii supplementation improves #cardio-metabolic health in subjects at risk for type 2 #diabetes.

The gut commensal Anaerobutyricum soehngenii is an anaerobe that can produce both propionate and butyrate, metabolites that have been shown to have a positive effect on gut and overall health. Murine and human dose finding studies have shown that oral intake of A. soehngenii has a positive influence on peripheral insulin resistance, thereby reducing the risk of type 2 diabetes. A recent human intervention provided support for the mode of action of A. soehngenii as it affected gene expression in the duodenum, stimulated the secretion of GLP‐1 and improved insulin sensitivity. For these reasons A. soehngenii has been proposed as a food ingredient. Before introducing this bacterium to the food chain, however, it must be established that oral intake of live A. soehngenii bacteria does not pose any health risk. As part of the safety analysis of A. soehngenii strain CH106, we performed genotoxicity assays to determine its mutagenic potential (bacterial reverse mutation and in vitro mammalian cell micronucleus tests) and a 90‐day subchronic toxicity study in rats to determine overall toxicity potential. The results of both genotoxicity studies were negative, showing no genotoxic effects. For the 90‐day subchronic toxicity study, no adverse events were registered that could be attributed to the feeding with A. soehngenii strain CH106. Even at the highest dose, which exceeds the expected daily human intake more than 100‐fold, no adverse events were observed. These result support the conclusion that the use of A. soehngenii strain CH106 as a food ingredient is safe.