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

Zhiyi Liu,Yunfei Luo,Qiongfeng Chen,Wangdi Liao,Zihan Zhang,Ruiling Lu,Ruipu Sun,Ying Ying,Xin Li

doi:10.3389/fphar.2021.640347

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.

Highlights

Inflammatory bowel disease (IBD), characterized by chronic inflammatory disorders of the colon and small intestine, are common and widespread
The gut microbiota profiles revealed that the biodiversity of intestinal flora lost during inflammation was restored under metformin treatment
These results show that metformin administration can counteract colitis’s negative impacts on body weight and colon length in Dextran Sulfate Sodium (DSS)-induced colitis mice

Summary

Introduction

Inflammatory bowel disease (IBD), characterized by chronic inflammatory disorders of the colon and small intestine, are common and widespread. Evidence has been reported in both human and animal studies for a potential role for imbalance among gut microbiota in the pathogenic mechanisms of IBD (Matsuoka and Kanai, 2015; Nishida et al, 2018). The majority of colitis lesions in IBD patients are located in segments where gut microbes are highly concentrated, significantly associated with fecal accumulation, such as the colorectal terminal segment (Ni et al, 2017). Inflammatory bowel disease (IBD) is an increasingly common and globally emergent immune-mediated disorder. Metformin is widely used to treat type 2 diabetes and has shown beneficial effects in mouse models of IBD, its underlying mechanisms remain poorly understood. This study explores possible regulatory effects of metformin on intestinal microecology during treatment for IBD

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Results

Discussion

Conclusion