Bombyx mori silk fibroin alleviates alcohol-induced liver injury via modulation of the gut-liver axis.

Alcohol-induced liver disease (ALD) remains a major global health burden with limited therapeutic options. Modulating the gut microbiota has emerged as a promising strategy for ameliorating ALD. Bombyx mori silk fibroin (SF), an animal-derived protein with demonstrated gut microbiota-modulating properties, has shown potential in metabolic disease models, yet the mechanisms underlying its hepatoprotective effects against ALD remain poorly understood. In this study, we established an acute alcoholic liver injury (AALI) mouse model to investigate whether orally administered SF attenuates AALI through modulation of the gut-liver axis. SF supplementation improved lipid profiles and hepatic function, and alleviated hepatic oxidative stress and inflammatory responses. Antibiotic clearance experiments revealed that these protective effects were dependent on an intact gut microbiota. SF treatment also preserved colonic expression of the tight junction proteins ZO-1 and Occludin in a microbiota-dependent manner. Gut microbiota and metabolomic analyses further showed that SF promoted the proliferation of beneficial genera, including Alistipes, norank_f__Oscillospiraceae, and Colidextribacter, while inhibiting potentially harmful genera such as Staphylococcus and Romboutsia. These microbial changes were accompanied by the upregulation of beneficial metabolites, including acetylcholine, ethyl 4-pentenoate, 12-hydroxydodecanoic acid, PGF2a ethanolamide, and kinetensin 4-7. Collectively, these findings demonstrate that SF alleviates AALI through modulation of the gut microbiota and its metabolic output, with preservation of intestinal barrier integrity serving as an integral component of this gut-liver axis-mediated mechanism.