Is Associated with Disease Severity in MASLD but Its Supplementation Does Not Improve Diet-Induced Steatohepatitis in Mice.

The gut microbiota plays an important role in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). In this study, we aimed to evaluate the role of the butyrate-producing bacterium in MASLD and whether supplementation with butyrate-producing bacteria, in particular , can ameliorate diet-induced steatohepatitis in mice. The relative abundance of the genus and its most abundant strain was determined by 16S rRNA sequencing and quantitative polymerase chain reaction (qPCR), respectively, in 95 participants with MASLD and 19 healthy control subjects. Butyrate and butyrate-producing bacteria ( and ) were gavaged to C57BL/6 mice fed a steatohepatitis-inducing diet. The fecal relative abundance of and was decreased in subjects with MASLD versus healthy controls and lower in individuals with MASLD and stage 3-4 fibrosis versus those with stage 0-2 fibrosis. Sodium-butyrate supplementation improved hepatic steatosis in mice on high-fat diet (HFD). Gavage of various butyrate-producing bacteria including and isolated from humans did not improve HFD-induced liver disease in mice. Although the abundance of is associated with MASLD severity in humans, its gavage to mice does not improve experimental diet-induced liver disease.