Faecalibacterium prausnitzii 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 <i>Faecalibacterium prausnitzii</i> in MASLD and whether supplementation with butyrate-producing bacteria, in particular <i>Faecalibacterium prausnitzii</i>, can ameliorate diet-induced steatohepatitis in mice. The relative abundance of the genus <i>Faecalibacterium</i> and its most abundant strain <i>Faecalibacterium prausnitzii</i> 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 (<i>Faecalibacterium prausnitzii</i> and <i>Coprococcus comes</i>) were gavaged to C57BL/6 mice fed a steatohepatitis-inducing diet. The fecal relative abundance of <i>Faecalibacterium</i> and <i>Faecalibacterium prausnitzii</i> 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 <i>Faecalibacterium prausnitzii</i> and <i>Coprococcus comes</i> isolated from humans did not improve HFD-induced liver disease in mice. Although the abundance of <i>Faecalibacterium prausnitzii</i> is associated with MASLD severity in humans, its gavage to mice does not improve experimental diet-induced liver disease.