Duodenal Anaerobutyricum soehngenii infusion stimulates GLP-1 production, ameliorates glycaemic control and beneficially shapes the duodenal transcriptome in metabolic syndrome subjects: a randomised double-blind placebo-controlled cross-over study

Abstract

ObjectiveAlthough gut dysbiosis is increasingly recognised as a pathophysiological component of metabolic syndrome (MetS), the role and mode of action of specific gut microbes in metabolic health remain elusive. Previously, we identified the commensal butyrogenic Anaerobutyricum soehngenii to be associated with improved insulin sensitivity in subjects with MetS. In this proof-of-concept study, we investigated the potential therapeutic effects of A. soehngenii L2-7 on systemic metabolic responses and duodenal transcriptome profiles in individuals with MetS.DesignIn this randomised double-blind placebo-controlled cross-over study, 12 male subjects with MetS received duodenal infusions of A. soehngenii/ placebo and underwent duodenal biopsies, mixed meal tests (6 hours postinfusion) and 24-hour continuous glucose monitoring.ResultsA. soehngenii treatment provoked a markedly increased postprandial excursion of the insulinotropic hormone glucagon-like peptide 1 (GLP-1) and an elevation of plasma secondary bile acids, which were positively associated with GLP-1 levels. Moreover, A. soehngenii treatment robustly shaped the duodenal expression of 73 genes, with the highest fold induction in the expression of regenerating islet-protein 1B (REG1B)-encoding gene. Strikingly, duodenal REG1B expression positively correlated with GLP-1 levels and negatively correlated with peripheral glucose variability, which was significantly diminished in the 24 hours following A. soehngenii intake. Mechanistically, Reg1B expression is induced upon sensing butyrate or bacterial peptidoglycan. Importantly, A. soehngenii duodenal administration was safe and well tolerated.ConclusionsA single dose of A. soehngenii improves peripheral glycaemic control within 24 hours; it specifically stimulates intestinal GLP-1 production and REG1B expression. Further studies are needed to delineate the specific pathways involved in REG1B induction and function in insulin sensitivity.Trial registration numberNTR-NL6630.

Gut microbiome and health: mechanistic insights

“…Moreover, duodenal perfusions of live or dead Lactobacillus spp have been found to affect the host immune response, providing an experimental system for human discovery 27–29. This has been recently exploited for the analysis of a single duodenal dose of Anaerobutyricum soehngenii (previously known as Eubacterium hallii )30 that increased the duodenal expression level of the gene for regenerating islet-protein 1B almost 10-fold and also increased serum glucagon-like peptide-1 (GLP-1) and secondary bile salts in metabolic syndrome subjects, thereby potentially explaining their improved response to glucose 31 32…”

The probiotic Bacillus subtilis BS50 decreases gastrointestinal symptoms in healthy adults: a randomized, double-blind, placebo-controlled trial

“… 59 However, it is the acute response and contribution of GLP-1 to insulin regulation that is traditionally studied in oral glucose and meal challenges. In this context, the probiotic strains Limosilactobacillus reuteri SD5865 (formerly Lactobacillus reuteri ) and Anaerobutyricum soehngenii CH106 have been shown to beneficially increase acute postprandial GLP-1 response following oral supplementation and duodenal infusion, respectively, in clinical trials, 60 , 61 as well as other strains in animal studies. 62 , 63 Many clinical trials of probiotic supplementation have shown direct benefits on blood glucose control in patients with diabetes.…”

Microbial lactate utilisation and the stability of the gut microbiome

“…Importantly, the probiotic could be detected in stool samples provided by the recipients, suggesting survival through the gastrointestinal tract, and was deemed safe. Duodenal infusion of A. soehngenii in individuals with metabolic syndrome revealed that it stimulated the insulinotropic hormone glucagon-like peptide 1 production and increased expression of regenerating islet-protein 1B (Koopen et al, 2021).…”