Holdemanella biformis improves glucose tolerance via GLP-1 signalling in diet-induced obese mice

Impaired glucose homeostasis in obesity is ameliorated by enhancing the glucoregulatory actions of glucagon-like peptide 1 (GLP-1). Strategies that enhance the endogenous GLP-1 sensitivity and its secretion have a translational potential for type 2 diabetes (T2D). Diverse microbial by-products derived from dietary macronutrients are GLP-1 enhancers, although the involved intestinal bacteria remain almost unexplored. Holdemanella biformis, isolated from feces of lean and metabolically healthy volunteer participating in an observational study focused on obesity, reduced hyperglycemia, improved oral glucose tolerance and prevented the impaired gluconeogenesis and insulin signalling in liver of diet-induced obese mice. Additionally, H.biformis restored the impaired circulating levels of GLP-1, modulated the GLP-1-mediated neural signalling in ileum and colon, enhanced the GLP-1 sensitivity of cultured nodose ganglion neurons and influenced the cecal abundance of acetate, oleic acid and a-linolenic acid, GLP-1 secretagogues. Our data open a novel H.biformis-based strategy to combat T2D by modulating the GLP-1 system.