Saccharomyces Boulardii Ameliorates Non-alcoholic Steatohepatitis in Mice Induced by a Methionine-Choline-Deficient Diet Through Gut-Liver Axis

Abstract

Non-alcoholic steatohepatitis (NASH) is affecting people worldwide. Changes in the intestinal microbiome are crucial to NASH. A previous study showed that eradicating intestinal fungi ameliorates NASH; however, the role of intestinal fungi in the development of NASH remains unclear. <i>Saccharomyces boulardii (SB)</i>, a dietary supplement yeast, has been reported to restore the integrity of the intestine. Here, we tested the effect of <i>SB</i> in the treatment of NASH. For this study, we fed eight-week-old C57/BL6 male mice either a methionine-choline deficient (MCD) diet or a normal chow diet (NCD) for eight weeks. Half of the MCD diet-fed mice were gavaged with SB (5 mg/day) once daily. The remainder of the NCD-fed mice were gavaged with normal saline as a control. The MCD diet-fed mice on <i>SB</i> supplement showed better liver function, less hepatic steatosis, and decreased inflammation. Both hepatic inflammatory gene expression and fibrogenic gene expression were suppressed in mice with <i>SB</i> gavage. Intestinal damage caused by the MCD diet was tampered with, intestine inflammation decreased, and gut permeability improved in mice that had been given the <i>SB</i> supplement. Deep sequencing of the fecal microbiome showed a potentially increased beneficial gut microbiota and increased microbiota diversity in the <i>SB</i>-supplemented mice. The <i>SB</i> supplement maintains gut integrity, increases microbial diversity, and increases the number of potentially beneficial gut microbiota. Thus, the <i>SB</i> supplement attenuates gut leakage and exerts a protective effect against NASH. Our results provide new insight into the prevention of NASH.