Pastor-Villaescusa, BelénPlaza-Díaz, JulioEgea-Zorrilla, AlejandroLeis, RosauraBueno, GloriaHoyos, RaúlVázquez-Cobela, RocíoLatorre, MiriamCañete, María DoloresCaballero-Villarraso, JavierGil, ÁngelCañete, RamónAguilera, Concepción María2022-11-212022-11-212020-12-24Pastor-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;134:111117.0753-3322http://hdl.handle.net/10668/4375Background 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. Methods 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. Results 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. Conclusion 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/MetforminMicrobiotaChildren populationPubertal stageObesityHealthy lifestyleGut microbiotaVerrucomicrobiaActinobacteriaBacteroidetesFirmicutesBacillusMetforminaNiñoObesidadEstilo de vida saludableMicrobioma gastrointestinalEnsayo clínico controlado aleatorioMedical Subject Headings::Persons::Persons::Age Groups::AdolescentMedical Subject Headings::Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Epidemiologic Factors::Age FactorsMedical Subject Headings::Organisms::BacteriaMedical Subject Headings::Persons::Persons::Age Groups::ChildMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Research Design::Double-Blind MethodMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Hypoglycemic AgentsMedical Subject Headings::Anatomy::Digestive System::Gastrointestinal Tract::IntestinesMedical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Life StyleMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amidines::Guanidines::Biguanides::MetforminMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity::Pediatric ObesityMedical Subject Headings::Geographical Locations::Geographic Locations::Europe::SpainMedical Subject Headings::Phenomena and Processes::Physical Phenomena::Time::Time FactorsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment OutcomeMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::MetagenomeMedical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Genetics::Genomics::MetagenomicsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Principal Component AnalysisMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Research Design::Sample SizeMedical Subject Headings::Organisms::Bacteria::VerrucomicrobiaMedical Subject Headings::Organisms::Bacteria::Gram-Positive Bacteria::ActinobacteriaMedical Subject Headings::Organisms::Bacteria::BacteroidetesMedical Subject Headings::Organisms::Bacteria::Endospore-Forming Bacteria::Gram-Positive Endospore-Forming Bacteria::Gram-Positive Endospore-Forming Rods::Bacillaceae::BacillusMedical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Feeding BehaviorMedical Subject Headings::Publication Type::Study Characteristics::Clinical Trial::Randomized Controlled Trialresearch article33360047open access10.1016/j.biopha.2020.1111171950-6007