Effects of three Huanglian-derived polysaccharides on the gut microbiome and fecal metabolome of high-fat diet/streptozocin-induced type 2 diabetes mice

Plant-derived polysaccharides are important components for biological functions. The objective of this study is to study the mechanisms by which polysaccharides from three Huanglian (Rhizome Coptidis, HL) of Coptis chinensis, C. deltoidea, and Coptis teeta affect type 2 diabetes mellitus (T2DM) by analyzing the gut microbiome and their metabolites. A long-term high-fat diet (HFD) combined with streptozocin (STZ) induction was used to construct the T2DM mice model. The histopathology of liver, pancreas, and colon, biochemical indexes related to mice were determined to assess the ameliorative effects of these three HL polysaccharides (HLPs) on T2DM. The results indicated that oral HLPs improved hyperglycemia, insulin resistance, blood lipid levels, and β-cell function. Further, HLPs elevated the growth of advantageous beneficial bacteria within the gut microbiota and raised the concentrations of short-chain fatty acids (SCFAs), particularly butyric acid. Metabolic analyses showed that HLPs ameliorated the effects of T2DM on microbial-derived metabolites and related metabolic pathways, especially the biosynthetic pathways of phenylalanine, tyrosine, and tryptophan. In the combined analysis, many associations of T2DM-related biochemical indicators with gut microbes and their metabolites were extracted, which suggested the important role of gut microbiome and fecal metabolome in the amelioration of type 2 diabetes mellitus by HLPs.