Si-Wu-Tang Targets Microbiota Homeostasis and Intestinal Mucosal Barriers to Provide Protection Against MASLD by Favoring P. goldsteinii-like Taxa Colonization.

Objective: This study examined the pharmacological mechanisms of the therapeutic benefits of SWT to MASLD via regulating the gut-liver axis. Methods: The components of SWT were analyzed by liquid chromatograph mass spectrometer (LC-MS). After establishing an MCD-induced MASLD mice model, we invested the protective mechanism of SWT through 16S rRNA sequencing combined with molecular biological experiments. After eliminating the intestinal microbiota through an antibiotic cocktail experiment, we identified the key microbiota by which SWT improves MASLD. Results: SWT markedly reduced MASLD injury by alleviating intestinal inflammation and restoring the intestinal mucosal barrier, which could be reversed following alcohol exposure. Additionally, SWT altered the intestinal flora of MASLD mice, significantly raising the relative abundance of Parabacteroides goldsteinii-like taxa, while alcohol caused the destruction of P. goldsteinii-like-taxa-centered probiotic habitats and a proliferation of pathogenic bacteria, especially Bacteroides intestinalis-like taxa. After the elimination of intestinal flora, the anti-MASLD effect of SWT was lost. Moreover, the supplement of P. goldsteinii could significantly ameliorate liver damage caused by an MCD diet, functioning similarly to SWT. However, the liver-protective effect of SWT was suppressed following the administration of B. intestinalis. Conclusions: SWT ameliorates MCD diet-induced MASLD via modulating intestinal microbiota homeostasis and restoring intestinal mucosal barriers. Given that P. goldsteinii is effective for treating MASLD, it provides insights into new therapeutic strategies.