<i>Anaerobutyricum soehngenii</i> improves glycemic control and other markers of cardio-metabolic health in adults at risk of type 2 diabetes

<i>Anaerobutyricum soehngenii</i> (previously <i>Eubacterium hallii</i>) is a butyrate-producing next-generation beneficial microbe generally recognized as safe. Several short-term intervention trials by <i>A. soehngenii</i> 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 <i>A. soehngenii</i> CH-106, a tetracycline-sensitive isogenic derivative of strain L2-7. Compared to placebo, <i>A. soehngenii</i>-treated subjects showed significantly reduced glycemic variability (1% reduction in the coefficient of variation; <i>p</i> = 0.01) and improved glycemic control (6% reduction in the overall net glycemic action-1; <i>p</i> < 0.05), including reduced serum glycated hemoglobin (HbA1c) levels when including the 4-week washout period (1 mmol/mol reduction; <i>p</i> < 0.05). Moreover, diastolic blood pressure was significantly reduced in all <i>A. soehngenii</i>-treated subjects (3 mm Hg; <i>p</i> < 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 <i>A. soehngenii</i> 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; <i>p</i> = 0.039) or coefficient of variation (reduction of 3.1%; <i>p</i> < 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 <i>Bifidobacterium, Coprococcus</i>, <i>Ruminococcus</i> spp. and two-fold increased relative abundance of <i>Lachnoclostridium</i> spp. In conclusion, daily oral supplementation with <i>A. soehngenii</i> 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.<b>Clinical trial reg. no.</b> NCT04529473, clinicaltrials.gov<b>Social media summary 120 characters:</b> <i>Anaerobutyricum soehngenii</i> supplementation improves #cardio-metabolic health in subjects at risk for type 2 #diabetes.