RT Journal Article T1 Evaluation of the gut microbiota after metformin intervention in children with obesity: A metagenomic study of a randomized controlled trial A1 Pastor-Villaescusa, Belén A1 Plaza-Díaz, Julio A1 Egea-Zorrilla, Alejandro A1 Leis, Rosaura A1 Bueno, Gloria A1 Hoyos, Raúl A1 Vázquez-Cobela, Rocío A1 Latorre, Miriam A1 Cañete, María Dolores A1 Caballero-Villarraso, Javier A1 Gil, Ángel A1 Cañete, Ramón A1 Aguilera, Concepción María K1 Metformin K1 Microbiota K1 Children population K1 Pubertal stage K1 Obesity K1 Healthy lifestyle K1 Gut microbiota K1 Verrucomicrobia K1 Actinobacteria K1 Bacteroidetes K1 Firmicutes K1 Bacillus K1 Metformina K1 Niño K1 Obesidad K1 Estilo de vida saludable K1 Microbioma gastrointestinal K1 Ensayo clínico controlado aleatorio AB BackgroundMetformin, 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.MethodsThe 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.ResultsActinobacteria 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.ConclusionFurther 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. PB Elsevier Masson SAS SN 0753-3322 YR 2020 FD 2020-12-24 LK http://hdl.handle.net/10668/4375 UL http://hdl.handle.net/10668/4375 LA en NO Pastor-Villaescusa B, Plaza-Díaz J, Egea-Zorrilla A, Leis R, Bueno G, Hoyos R, et al. Evaluation of the gut microbiota after metformin intervention in children with obesity: A metagenomic study of a randomized controlled trial. Biomed Pharmacother. 2020 Dic;134:111117. DS RISalud RD Apr 9, 2025