Evaluation of the gut microbiota after metformin intervention in children with obesity: A metagenomic study of a randomized controlled trial

[Display omitted] •In obesity, gut microbiota is altered, playing a role in its pathophysiology.•Lifestyle behaviors have a potential impact on gut microbiota.•Metformin alters gut microbiota in diabetic people; in obesity, it is still unknown.•A metformin intervention might modify gut microbiota in children with obesity. Metformin, a first-line oral antidiabetic agent that has shown promising results in terms of treating childhood and adolescent obesity, might influence the composition of the gut microbiota. We aimed to evaluate whether the gut microbiota of non-diabetic children with obesity changes after a metformin intervention. The study was a multicenter and double-blind randomized controlled trial in 160 children with obesity. Children were randomly assigned to receive either metformin (1 g/day) or placebo for 6 months in combination with healthy lifestyle recommendations in both groups. Then, we conducted a metagenomic analysis in a subsample obtained from 33 children (15 metformin, 18 placebo). A linear mixed-effects model (LMM) was used to determine the abundance changes from baseline to six months according to treatment. To analyze the data by clusters, a principal component analysis was performed to understand whether lifestyle habits have a different influence on the microbiota depending on the treatment group. Actinobacteria abundance was higher after placebo treatment compared with metformin. However, the interaction time x treatment just showed a trend to be significant (4.6% to 8.1% after placebo vs. 3.8 % to 2.6 % after metformin treatment, p = 0.055). At genus level, only the abundance of Bacillus was significantly higher after the placebo intervention compared with metformin (2.5% to 5.7% after placebo vs. 1.5 % to 0.8 % after metformin treatment, p = 0.044). Furthermore, different ensembles formed by Firmicutes, Bacteroidetes, and Verrucomicrobia were found according to the interventions under a similar food consumption. Further studies with a large sample size controlled by lifestyle patterns are required in obese children and adolescents to clarify whether metformin might trigger gut microbiota alterations. Trial Registration: Registered on the European Clinical Trials Database (EudraCT, ID: 2010−023061-21) on 14 November 2011.