Abstract
BackgroundMetformin is a widely used first-line drug for treatment of type 2 diabetes. Despite its advantages, metformin has variable therapeutic effects, contraindications, and side effects. Here, for the very first time, we investigate the short-term effect of metformin on the composition of healthy human gut microbiota.MethodsWe used an exploratory longitudinal study design in which the first sample from an individual was the control for further samples. Eighteen healthy individuals were treated with metformin (2 × 850 mg) for 7 days. Stool samples were collected at three time points: prior to administration, 24 hours and 7 days after metformin administration. Taxonomic composition of the gut microbiome was analyzed by massive parallel sequencing of 16S rRNA gene (V3 region).ResultsThere was a significant reduction of inner diversity of gut microbiota observed already 24 hours after metformin administration. We observed an association between the severity of gastrointestinal side effects and the increase in relative abundance of common gut opportunistic pathogen Escherichia-Shigella spp. One week long treatment with metformin was associated with a significant decrease in the families Peptostreptococcaceae and Clostridiaceae_1 and four genera within these families.ConclusionsOur results are in line with previous findings on the capability of metformin to influence gut microbiota. However, for the first time we provide evidence that metformin has an immediate effect on the gut microbiome in humans. It is likely that this effect results from the increase in abundance of opportunistic pathogens and further triggers the occurrence of side effects associated with the observed dysbiosis. An additional randomized controlled trial would be required in order to reach definitive conclusions, as this is an exploratory study without a placebo control arm. Our findings may be further used to create approaches that improve the tolerability of metformin.
Highlights
Metformin is a biguanide agent that is widely used as a first-line treatment of type 2 diabetes (T2D) [1]
There was a significant reduction of inner diversity of gut microbiota observed already 24 hours after metformin administration
One participant withdrew from the trial at the fifth day of metformin administration due to severe GI side effects
Summary
Metformin is a biguanide agent that is widely used as a first-line treatment of type 2 diabetes (T2D) [1]. A delayed-release formulation of metformin improves glycemic control to the same extent as the immediate-release form despite lower systemic exposure [9]. These findings have led to the hypothesis that the effects of metformin are partially explained by its interaction with the gut microbiome. The connection between the effects of metformin and the gut microbiome has been supported by several recent studies [10,11,12,13,14,15,16,17] These studies suggest that the gut microbiome is involved in both the therapeutic and side effects of the drug, yet details of this interaction remain obscure. For the very first time, we investigate the short-term effect of metformin on the composition of healthy human gut microbiota
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
