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

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

doi:10.3389/fphar.2021.640347

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

Front Pharmacol. 2021 May 21:12:640347. doi: 10.3389/fphar.2021.640347. eCollection 2021.

Authors

Zhiyi Liu^{1

2}, Wangdi Liao³, Zihan Zhang^{1

2}, Ruipu Sun^{1

2}, Yunfei Luo⁴, Qiongfeng Chen⁴, Xin Li³, Ruiling Lu³, Ying Ying^{1

4

5}

Affiliations

¹ Jiangxi Institute of Respiratory Disease, The First Affiliated Hospital of Nanchang University, Nanchang, China.
² Queen Mary School, Nanchang University, Nanchang, China.
³ Departments of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
⁴ Department of Pathophysiology, Schools of Basic Medical Sciences, Nanchang University, Nanchang, China.
⁵ The Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, China.

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.

Keywords: anti-inflammatory effect; biodiversity; gut microbiota; inflammatory bowel disease; metformin.