Shenling Jianpiwei formula ameliorates metabolic associated fatty liver disease through modulation of the gut microbiota and attenuation of LPS-mediated inflammation.

The gut microbiota and its products are recognized as pivotal contributors to the pathogenesis of metabolic-associated fatty liver disease (MAFLD). Shenling Jianpiwei formula (SLJPW), a prescription renowned for its protective effects in intestinal disorders, demonstrates efficacy against MAFLD. However, its underlying mechanisms and chemical composition remain unclear. In this study, SLJPW treatment significantly alleviated high-fat diet-induced weight gain, lipid accumulation, liver injury, inflammation, and oxidative stress in MAFLD rats. And also markedly restored gut microbiota dysbiosis, primarily characterized by an increase in Lactobacillus and Allobaculum, a decrease in Spirochaetes and Collinsella, and alterations in microbial functional pathways. Moreover, SLJPW treatment reversed the abundance of gut microbes associated with MAFLD pathological parameters, particularly by reducing the abundance of microbes positively correlated with LPS and NF-κB. Through UHPLC-Q-TOF-MS analysis, 37 constituents in SLJPW were successfully determined, including triterpenes, flavonoids, and phenolic acids. Based on network pharmacology analysis, TNF, CASP3, and STAT3, as well as 11 compounds from SLJPW and metabolites derived from Lactobacillus, were implicated in the therapeutic effects of SLJPW on MAFLD. Crucially, the efficacy of SLJPW was substantially diminished in antibiotic-induced pseudo-germ-free MAFLD rats, highlighting the essential role of the gut microbiota in its therapeutic effects. Collectively, this study presents a novel finding that most of the anti-MAFLD effects of SLJPW is gut microbiota-dependent.