Metformin Affects Gut Microbiota Composition and Diversity Associated with Amelioration of Dextran Sulfate Sodium-Induced Colitis in Mice

Abstract

Background: Inflammatory bowel disease (IBD) is an increasingly common and globally emergent immune-mediated disorder. The etiology of IBD is complex, involving multiple factors such as immune dysregulation, environmental factors, genetic mutations, and microbiota dysbiosis, exacerbated by a lack of effective clinical therapies. Recently, studies hypothesized that dysbiosis of intestinal flora might participate in the onset of IBD. Metformin is widely used to treat type 2 diabetes and has shown beneficial effects in mouse models of IBD, although its underlying mechanisms remain poorly understood. Accumulating studies found that metformin shows beneficial effects for diabetes by affecting microbiota composition. This study explores possible regulatory effects of metformin on intestinal microecology during treatment for IBD.Methods: Inflammation was induced using 3% Dextran Sulfate Sodium (DSS) solution to generate mice models of IBD. Metformin treatments were assayed by measuring body weights and colon lengths of mice and H&E staining to observe histological effects on colon tissue structures. Changes in bacterial community composition and diversity-related to IBD and metformin treatment were assessed by high-throughput metagenomic sequencing analysis.Results: Metformin administration significantly ameliorated body weight loss, inhibited colon shrinking, and contributed to preserving the integrity of colon histological structures. The gut microbiota profiles revealed that the biodiversity of intestinal flora lost during inflammation was restored under metformin treatment. Metformin administration was also associated with decreased pathogenic Escherichia shigella and increased abundance of Lactobacillus and Akkermansia.Conclusion: Metformin appears to induce anti-inflammatory effects, thus ameliorating colitis symptoms, concurrent with enrichment for beneficial taxa and restored microbial diversity, suggesting a viable strategy against IBD.

Effects of Oral Glucose-Lowering Agents on Gut Microbiota and Microbial Metabolites

“…In addition to clinical studies on T2DM patients, a clinical trial which recruited 20 healthy Korean participants found that metformin treatment altered the abundances of Clostridium , Escherichia , Intestinibacter , and Romboutsia , and the relative abundances of metabolites changed including carbohydrate, fatty acid, and amino acid metabolism ( 95 ). In experimental animal models, treatment with metformin was revealed to increase SCFA production, to reduce circulation LPS, to inhibit intestinal proinflammatory signaling activities, which was in line with clinical studies ( 80 , 96 , 97 ) ( Figure 2 ). The activation of SCFA receptors, GPR41 and GPR43, stimulated the secretion of PYY and GLP-1, inhibiting appetite and improving insulin secretion.…”

Alterations in the Gut Microbiota and Hepatitis-B-Virus Infection in Southern Chinese Patients With Coexisting Non-Alcoholic Fatty Liver Disease and Type-2 Diabetes Mellitus

“…The diversity and richness of bacteria in the gut are important for maintaining intestinal homeostasis, the intestinal mucosal barrier, the immune system, and metabolism of the host. Reduced diversity is a characteristic of microbiota dysbiosis (21)(22)(23). In this work, α-diversity and β-diversity were reduced significantly in patients with coexistent HBV infection, NAFLD, and T2DM.…”

Akkermansia muciniphila in inflammatory bowel disease and colorectal cancer

“…Enrichment of A. muciniphila following metformin treatment has been found to frequently coincide with alleviated colonic inflammation in colitis mice. [ 11 ] TAK-242 (resatorvid), an inhibitor of Toll-like receptor 4 (TLR4), was reported to exhibit therapeutic potential in UC by regulating the gut microbiota and promoting the growth of A. muciniphila . Hyaluronic acid-bilirubin nanomedicine has been found to be associated with enrichment of A. muciniphila , regulate innate immune responses, and exert potent therapeutic efficacy against colitis.…”