Abstract
In recent years, the first-line anti-diabetic drug metformin has been shown to be also useful for the treatment of other diseases like cancer. To date, few reports were about the impact of metformin on gut microbiota. To fully understand the mechanism of action of metformin in treating diseases other than diabetes, it is especially important to investigate the impact of long-term metformin treatment on the gut microbiome in non-diabetic status. In this study, we treated healthy mice with metformin for 30 days, and observed 46 significantly changed gut microbes by using the 16S rRNA-based microbiome profiling technique. We found that microbes from the Verrucomicrobiaceae and Prevotellaceae classes were enriched, while those from Lachnospiraceae and Rhodobacteraceae were depleted. We further compared the altered microbiome profile with the profiles under various disease conditions using our recently developed comparative microbiome tool known as MicroPattern. Interestingly, the treatment of diabetes patients with metformin positively correlates with colon cancer and type 1 diabetes, indicating a confounding effect on the gut microbiome in patients with diabetes. However, the treatment of healthy mice with metformin exhibits a negative correlation with multiple inflammatory diseases, indicating a protective anti-inflammatory role of metformin in non-diabetes status. This result underscores the potential effect of metformin on gut microbiome homeostasis, which may contribute to the treatment of non-diabetic diseases.
Highlights
Metformin, known as 1,1-dimethylbiguanide has been widely used in the treatment of type 2 diabetes mellitus (T2DM) since 1958 in United Kingdom and 1995 in United States (Witters, 2001)
Could metformin alter gut microbiota of healthy individuals? How does metformin alter the gut microbiota of healthy individuals? What is the difference of the influence of metformin on gut microbiota under healthy and disease conditions? Does any correlation of microbiota alteration exist between different metformin treatment context? In our study, we treated healthy mice with metformin and found that metformin could prominently affect gut microbiota under healthy condition
Metformin shows a beneficial effect on gut microbiota in terms of improving disease condition in diabetic patients, our result cannot support the idea that metformin treatment of healthy mice could prevent diabetes-related gut microbiota disorder
Summary
Known as 1,1-dimethylbiguanide has been widely used in the treatment of type 2 diabetes mellitus (T2DM) since 1958 in United Kingdom and 1995 in United States (Witters, 2001). Because clinical investigations have shown that metformin has low Metformin Alters Gut Microbiota risk of hypoglycemia, modest weight loss, persistent antihyperglycemic effect and cardiovascular safety, it is approved as one of the first-line drugs for treating T2DM (Garber et al, 2013). It was shown in 2005 that metformin has the anti-cancer properties (Evans et al, 2005). It was reported that metformin has potentially anti-aging effects (Novelle et al, 2016)
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