The Gut Commensal Butyricimonas Virosa Modulates Gut Microbiota-Dependent Thiamine Metabolism and Attenuates Mouse Steatotic Liver Disease.

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common chronic liver disease. This study investigates the anti-MASLD effects of dietary prebiotic stachyose (STA) on disease progression identifying Butyricimonas virosa as a key bacterium boosted by STA supplementation. Oral gavage of B. virosa to high fat diet (HFD)-fed mice significantly suppresses the progression of MASLD and modulates gut microbiota composition. Integration of metagenomic and metabolomic data demonstrates that B. virosa treatment significantly enhances the production of thiamine monophosphate (TMP), as well as its conversion to thiamine and subsequent accumulation in the liver. The accumulation of hepatic thiamine further leads to elevated thiamine pyrophosphate (TPP) concentrations enhancing the activity of branched-chain α-keto acid dehydrogenase E1 subunit α (BCKDHA) associated with augmented degradation of branched chain amino acids (BCAAs). Administration of B. virosa compensates via production of gut bacterial-derived TMP for hepatic TPP deficiency in mice fed a thiamine-deficient HFD. A population-based analysis reveals an inverse correlation between plasma thiamine levels, abundances of bacterial genes involved in thiamine synthesis and metabolism, and phenotypes associated with MASLD, suggesting that key genes involved in fecal thiamine metabolism, as well as serum thiamine determination, may potentially serve as biomarkers for the diagnosis of MASLD.