BACKGROUND: Bile-Processed Rhizoma Coptidis (BPRC) is a processed products of Rhizoma Coptidis (RC) commonly used to treat type 2 diabetes mellitus (T2DM). However, the synergistic mechanism of its processing remains unknown. Current research indicates that the gut microbiota and its metabolites, such as short-chain fatty acids (SCFAs), are closely associated with the progression of T2DM.
PURPOSE: This study aims to investigate the effects of BPRC on the gut microbiota and its metabolite SCFAs in T2DM rats.
METHODS: T2DM rat model was induced by a high-fat diet (HFD) combined with streptozotocin (STZ), followed by a 4-week treatment with BPRC to observe its therapeutic effects. The impact of BPRC on the gut microbiota was studied through metagenomic sequencing. Quantitative analysis of SCFAs was conducted using GC-MS. Western blot and quantitative real-time PCR (qRT-PCR) were conducted to investigate the potential mechanisms of BPRC.
RESULTS: BPRC significantly improved insulin resistance in T2DM rats, downregulated levels of pancreatic cell apoptosis factors, and upregulated the abundance of Bacteroides uniformis, Bacteroides sp A1C1, Anaerostipes caccae, Alistipes finegoldii and Blautia sp.N6H1-15 in T2DM rats. Additionally, BPRC increased the levels of seven SCFAs in the intestines of T2DM rats. It activated intestinal TGR5, GPR41, GPR43, and GPR109a receptors, collectively upregulating GLP-1 protein expression, and exerted therapeutic effects on T2DM.
CONCLUSION: The results indicate that the synergistic mechanism of BPRC in treating T2DM is associated with modulating the gut microbiota, increasing SCFAs content in the intestines, and regulating intestinal GLP-1 production.
