Alleviating effects of noni fruit polysaccharide on hepatic oxidative stress and inflammation in rats under a high-fat diet and its possible mechanisms

Non-alcoholic fatty liver disease is associated with the gut microbiota, oxidative stress, and inflammation. We aimed to investigate the possible mechanism by which noni fruit polysaccharide (NFP) improved hepatic oxidative stress and inflammation in rats under a high-fat diet (HFD) by modulating short-chain fatty acids (SCFAs), intestinal barrier, and gut microbiota. Hepatic oxidative stress, inflammation, and gut dysbiosis in rats were induced through HFD feeding for 4 weeks, followed by intervention with NFP treatment (100 mg per kg bw) for 5 weeks. Results showed that NFP reduced body weight gain and improved lipid metabolism, hepatic oxidative stress, and inflammation in rats under HFD. Aside from these beneficial effects, NFP positively affected SCFAs production and reversed the HFD-induced gut dysbiosis as indicated by improved microbiota diversity and composition. The levels of Lactobacillus, Ruminococca-ceae_UCG_014, Parasutterella, Ruminococcus_1, and [Eubacte-rium]_coprostanoligenes_group improved, whereas the levels of Prevotella_9, Collinsella, Bacteroides, and Turicibacter decreased. Furthermore, NFP maintained the colonic barrier integrity (increased the mRNA relative expression of CCL5, ZO-1, and occludin in the colon, and decreased the serum CCL5 level), and decreased the serum lipopolysaccharide level. Thus, NFP may modulate the gut microflora and SCFAs production, reduce the permeability of colonic barrier and metabolic endotoxemia, thereby alleviating hepatic oxidative stress and inflammation in rats under HFD.