Schisandra chinensis polysaccharide prevents alcohol-associated liver disease in mice by modulating the gut microbiota-tryptophan metabolism-AHR pathway axis.

Polysaccharides are one of the main active components of Schisandra chinensis and have been shown to possess diverse biological activities. In this study, we investigated the preventive effect of Schisandra chinensis polysaccharide (SCP) on alcohol-associated liver disease (ALD) by chronic-plus-binge ethanol feeding and the underlying mechanisms. The results suggest that supplementation with SCP prevents ALD by modulating gut microbiota and tryptophan (Trp) metabolism. SCP significantly enriched intestinal Lactobacillus, especially Lactobacillus reuteri, restored the content of intestinal indole derivatives (TRM, IAA, ILA, IALD) that can activate the aromatic hydrocarbon receptor (AHR), increased the colon AHR pathway activity, repaired intestinal barriers damage, reduced the circulating LPS, and inhibited the liver inflammation, oxidative stress, and lipid accumulation. The in vitro Trp metabolizing capacity was used to selected for a strain of L.reuteri whose in vitro proliferation was similarly promoted by SCP. Importantly, the gavage of the L.reuteri increased intestinal TRM content in mice. In addition, its ALD preventive effects were consistent with SCP and dependent on the colon AHR pathway. Our findings confirm that SCP may prevent ALD by mudulating the gut microbial-Trp metabolism-AHR pathway axis, suggesting that supplementation with the prebiotic SCP is an effective way to prevent ALD.