Abstract:In order to investigate the effect and its possible mechanisms of noni fruit polysaccharide (NFP) intervention on glucose metabolism in mice fed with a high-fat diet (HFD). 30 male C57BL/6 mice were employed to an 8-week experiment, and the glucose metabolism-related indicators and the intestinal microbiota in the cecum of mice were analyzed and compared in this study. The results showed that compared with the normal control group, the fasting blood glucose (FBG) in mice of the Model group increased by 41.38%, 50.55%, 54.44%, and 42.45% respectively in the 2nd, 4th, 6th, and 8th weeks. The glucose tolerance of mice in the Model group was also damaged to some degrees. While supplementing 200 mg/kg of NFP could alleviate the increase in FBG and the damage of glucose tolerance caused by HFD. Furthermore, compared with the Model group, the insulin resistance index and glycated serum protein content in mice of the NFP group decreased significantly by 19.03% and 22.26% respectively (P < 0.05). Gut microbiota analysis indicated that the NFP intervention suppressed the HFD-induced increases in relative abundance of Faecalibaculum, Dubosiella, Lachnospiraceae_UCG-006, and norank_f_erysipelotrichaceae. Spearman correlation analysis revealed positive correlations between Lachnospiraceae_UCG-006, norank_f_erysipelotrichaceae, and Faecalibaculum with IR index, while negative correlations were observed for norank_f_muribaculaceae and Akkermansia with IR index. In conclusion, this study suggests that HFD-induced insulin resistance in mice was closely related to the disruption of the intestinal microbiota. NFP could alleviate insulin resistance by regulating the intestinal microbiota. This research provides an important reference for the study and development of related functional foods or drugs.