Bupleuri Radix Polysaccharides Alleviate MASLD by Regulating Muribaculaceae-Derived SCFAs in the Gut–Liver Axis

<i>Bupleuri radix</i> has demonstrated therapeutic potential in treating liver disorders, and polysaccharides are one of its main bioactive components; however, the effects of <i>Bupleuri radix</i> polysaccharides (BRP) on metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear. This study aimed to identify the BRP fractions with anti-MASLD activity and elucidate their underlying mechanisms. We prepared BRP and characterized its physicochemical properties. It markedly alleviated liver injury and restored intestinal barrier function in MASLD. The correlation analysis between transcriptomics and targeted metabolomics showed that BRP restored intestinal acetic acid and propionic acid, with acetic acid activating AMPK and propionic acid promoting cholesterol efflux and metabolism in the liver, thereby reducing lipid accumulation in hepatocytes. Mechanistically, 16S RNA sequencing and diversity analysis indicated that BRP enriched short chain fatty acids (SCFAs)-producing bacteria, such as the genus <i>Muribaculaceae</i>, and inhibited pro-inflammatory microbiota. Interestingly, <i>Paramuribaculum intestinale</i> (<i>P. intestinale</i>), a representative species in the genus <i>Muribaculaceae</i>, synergistically enhanced BRP in improving liver and colonic mucosal damage in MASLD. In conclusion, our findings revealed that BRP improved MASLD by regulating <i>Muribaculaceae</i>-derived SCFAs in the gut-liver axis and could be used in combination with probiotics as a novel therapeutic strategy for MASLD.