Structural elucidation of a highly branched -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 alpha-DGlcp and a single alpha(1 -> 6)-D-Glcp-alpha(1 -> 6)-D-Glcp branched unit for every three alpha(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 ethanolinduced 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 shortchain 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.