Structural elucidation of a highly branched α-D-glucan from Huangjiu and its hepatoprotective activity via gut microbiome regulation and intestinal barrier repairment

Polysaccharides in Huangjiu, a traditional fermented food, are expected to be potentially effective ingredients in protecting against alcoholic liver disease (ALD). Elucidating their precise structural and functional characteristics is essential for in-depth understanding of structure-activity relationships of hepatoprotective polysaccharides. Herein, a major polysaccharide component HJPS1-2 was purified from Huangjiu with an average molecular weight of 3.49 kDa. Structural analyses inferred that HJPS1-2 backbone was composed of (1 → 4)-linked α-D-Glcp and a single α(1 → 6)-D-Glcp-α(1 → 6)-D-Glcp branched unit for every three α(1 → 4)-D-Glcp. An ALD mouse model was further established to clarify the underlying effect of HJPS1-2 on ALD alleviation. Biochemical detection and histopathological assessment revealed that HJPS1-2 intervention remarkably improved ethanol-induced hepatic dysfunction and steatosis. HJPS1-2 treatment ameliorated gut microbiota dysbiosis of ALD mice in a dose-dependent manner, mainly manifested as restoration of microbial diversities, community structure and bacterial interaction patterns. Compared with ethanol group, the strikingly elevated intestinal short-chain fatty acids' levels and enhanced intestinal barrier function after HJPS1-2 intake might contribute to reduced serum and liver lipopolysaccharide levels and subsequently suppressed release of hepatic inflammatory cytokines, thus mitigating ALD. Collectively, this research supports the potential of food-derived polysaccharides to hinder the early formation and progression of ALD through maintaining intestinal homeostasis.