Duodenal infusion of Anaerobutyricum soehngenii ameliorates glycemic control and postprandial GLP-1 responses and alters the transcriptional profile of small intestine in subjects with metabolic syndrome.

The gut microbiota constitutes an important modulator of metabolic heath and an unbalanced microbiota is increasingly recognized as an important risk factor for metabolic disorders, such as obesity, insulin resistance and type 2 diabetes. Seeking for novel treatments to counteract insulin resistance and metabolic disturbances in obese subjects, we explore whether delivering a protective commensal bacteria (Anaerobutyricum soehngenii L2-7) directly into the small intestine of treatment-naïve subjects with metabolic syndrome would ameliorate glucose metabolism (NTR NL6630). We previously identified this butyrate-producing intestinal commensal to be associated with improved insulin sensitivity in metabolic syndrome subjects. Herein, we found that a single-dose of duodenal infusion containing A. soehngenii improved peripheral glucose control and stimulated the secretion of the hormone GLP-1, which is reported to positively act on both insulin secretion and sensitivity. Moreover, by RNA-seq, we found that A. soehngenii-treatment triggered a prominent alteration of the duodenal transcriptome with 73 genes being differentially expressed. Among these, the expression of regenerating islet-protein 1B-encoding gene (REG1B) was the most significantly unregulated by A. soehngenii administration. Strikingly, duodenal REG1B expression negatively correlated with peripheral glucose variability, which was significantly diminished by A. soehngeniiduodenal infusion. Altogether our findings disclose that a single-dose of A. soehngenii is sufficient to greatly impact the duodenal transcriptional profile and ameliorate glucose metabolism in metabolic syndrome individuals, likely through induction of intestinal GLP-1 production. Nonetheless, further studies are needed to delineate the specific pathways involved in induction of REG1B and GLP-1. Notably, duodenal administration of A. soehngenii was also safe and well-tolerated.