Gut Commensal Barnesiella Intestinihominis Ameliorates Hyperglycemia and Liver Metabolic Disorders

Adv Sci (Weinh). 2024 Dec 31:e2411181. doi: 10.1002/advs.202411181. Online ahead of print.

Abstract

Recent studies have highlighted the role of the gut microbiota in type 2 diabetes (T2D). Improving gut microbiota dysbiosis can be a potential strategy for the prevention and management of T2D. Here, this work finds that the abundance of Barnesiella intestinihominis is significantly decreased in the fecal of T2D patients from 2-independent centers. Oral treatment of live B. intestinihominis (LBI) considerably ameliorates hyperglycemia and liver metabolic disorders in HFD/STZ-induced T2D models and db/db mice. LBI-derived acetate has similar protective effects against T2D. Mechanistically, acetate enhances fibroblast growth factor 21 (FGF21) through inhibition of histone deacetylase 9 (HDAC9) to increase H3K27 acetylation at the FGF21 promoter. The screening puerarin from Gegen Qinlian decoction in a gut microbiota-dependent manner improved hyperglycemia and liver metabolic disorders by promoting the growth of B. intestinihominis. This study suggests that gut commensal B. intestinihominis and puerarin, respectively have the potential as a probiotic and prebiotic in the treatment of T2D.

Keywords: acetate; fibroblast growth factor 21; gut microbiota; histone deacetylase 9; puerarin; type 2 diabetes.