Evaluation of the gut microbiota after metformin intervention in children with obesity: A metagenomic study of a randomized controlled trial
Background: 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 afte...
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Elsevier
2021-02-01
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Series: | Biomedicine & Pharmacotherapy |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S075333222031310X |
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doaj-25644e777d8d4efd9fd13705e8e9d3dd |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Belén Pastor-Villaescusa Julio Plaza-Díaz Alejandro Egea-Zorrilla Rosaura Leis Gloria Bueno Raúl Hoyos Rocío Vázquez-Cobela Miriam Latorre María Dolores Cañete Javier Caballero-Villarraso Ángel Gil Ramón Cañete Concepción María Aguilera |
spellingShingle |
Belén Pastor-Villaescusa Julio Plaza-Díaz Alejandro Egea-Zorrilla Rosaura Leis Gloria Bueno Raúl Hoyos Rocío Vázquez-Cobela Miriam Latorre María Dolores Cañete Javier Caballero-Villarraso Ángel Gil Ramón Cañete Concepción María Aguilera Evaluation of the gut microbiota after metformin intervention in children with obesity: A metagenomic study of a randomized controlled trial Biomedicine & Pharmacotherapy Metformin Microbiota Children population Pubertal stage Obesity |
author_facet |
Belén Pastor-Villaescusa Julio Plaza-Díaz Alejandro Egea-Zorrilla Rosaura Leis Gloria Bueno Raúl Hoyos Rocío Vázquez-Cobela Miriam Latorre María Dolores Cañete Javier Caballero-Villarraso Ángel Gil Ramón Cañete Concepción María Aguilera |
author_sort |
Belén Pastor-Villaescusa |
title |
Evaluation of the gut microbiota after metformin intervention in children with obesity: A metagenomic study of a randomized controlled trial |
title_short |
Evaluation of the gut microbiota after metformin intervention in children with obesity: A metagenomic study of a randomized controlled trial |
title_full |
Evaluation of the gut microbiota after metformin intervention in children with obesity: A metagenomic study of a randomized controlled trial |
title_fullStr |
Evaluation of the gut microbiota after metformin intervention in children with obesity: A metagenomic study of a randomized controlled trial |
title_full_unstemmed |
Evaluation of the gut microbiota after metformin intervention in children with obesity: A metagenomic study of a randomized controlled trial |
title_sort |
evaluation of the gut microbiota after metformin intervention in children with obesity: a metagenomic study of a randomized controlled trial |
publisher |
Elsevier |
series |
Biomedicine & Pharmacotherapy |
issn |
0753-3322 |
publishDate |
2021-02-01 |
description |
Background: 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. |
topic |
Metformin Microbiota Children population Pubertal stage Obesity |
url |
http://www.sciencedirect.com/science/article/pii/S075333222031310X |
work_keys_str_mv |
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doaj-25644e777d8d4efd9fd13705e8e9d3dd2021-06-11T05:11:54ZengElsevierBiomedicine & Pharmacotherapy0753-33222021-02-01134111117Evaluation of the gut microbiota after metformin intervention in children with obesity: A metagenomic study of a randomized controlled trialBelén Pastor-Villaescusa0Julio Plaza-Díaz1Alejandro Egea-Zorrilla2Rosaura Leis3Gloria Bueno4Raúl Hoyos5Rocío Vázquez-Cobela6Miriam Latorre7María Dolores Cañete8Javier Caballero-Villarraso9Ángel Gil10Ramón Cañete11Concepción María Aguilera12Institute for Nutritional Medicine, Else Kröner-Fresenius-Center for Nutritional Medicine, School of Life Sciences, Technical University of Munich, 85354, Freising, Germany; Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071, Granada, Spain; Institute of Nutrition and Food Technology ''José Mataix'', Centre of Biomedical Research, University of Granada, Avda. Del Conocimiento s/n, 18016 Armilla, Granada, Spain; Corresponding authors at: Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071, Granada, Spain.Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071, Granada, Spain; Institute of Nutrition and Food Technology ''José Mataix'', Centre of Biomedical Research, University of Granada, Avda. Del Conocimiento s/n, 18016 Armilla, Granada, Spain; Instituto de Investigación Biosanitaria IBS.GRANADA, Complejo Hospitalario Universitario de Granada, Granada, 18014, Spain; Corresponding authors at: Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071, Granada, Spain.Institute of Nutrition and Food Technology ''José Mataix'', Centre of Biomedical Research, University of Granada, Avda. Del Conocimiento s/n, 18016 Armilla, Granada, SpainCIBEROBN (CIBER Physiopathology of Obesity and Nutrition), Instituto de Salud Carlos III, 28029, Madrid, Spain; Unit of Investigation in Nutrition, Growth and Human Development of Galicia, Paediatric Department, Clinic University Hospital of Santiago, University of Santiago de Compostela, Santiago de Compostela, 15706, SpainCIBEROBN (CIBER Physiopathology of Obesity and Nutrition), Instituto de Salud Carlos III, 28029, Madrid, Spain; Pediatric Department, Lozano Blesa University Clinical Hospital, University of Zaragoza, Zaragoza, 50009, SpainPediatric Department, Virgen de Las Nieves University Hospital, Andalusian Health Service, Granada, 18014, SpainUnit of Investigation in Nutrition, Growth and Human Development of Galicia, Paediatric Department, Clinic University Hospital of Santiago, University of Santiago de Compostela, Santiago de Compostela, 15706, SpainPediatric Department, Lozano Blesa University Clinical Hospital, University of Zaragoza, Zaragoza, 50009, Spain; Pediatric Department and Health Sciences Institute in Aragon, Zaragoza, 50009, SpainPAIDI CTS-329, Maimonides Institute of Biomedical Research of Córdoba (IMIBIC), Córdoba, 14004, SpainClinical Analysis Services, IMIBIC/Reina Sofía Hospital, Córdoba University, Córdoba, 14004, SpainDepartment of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071, Granada, Spain; Institute of Nutrition and Food Technology ''José Mataix'', Centre of Biomedical Research, University of Granada, Avda. Del Conocimiento s/n, 18016 Armilla, Granada, Spain; Instituto de Investigación Biosanitaria IBS.GRANADA, Complejo Hospitalario Universitario de Granada, Granada, 18014, Spain; CIBEROBN (CIBER Physiopathology of Obesity and Nutrition), Instituto de Salud Carlos III, 28029, Madrid, SpainPAIDI CTS-329, Maimonides Institute of Biomedical Research of Córdoba (IMIBIC), Córdoba, 14004, Spain; Unit of Paediatric Endocrinology, Reina Sofia University Hospital, Córdoba, 14004, SpainDepartment of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071, Granada, Spain; Institute of Nutrition and Food Technology ''José Mataix'', Centre of Biomedical Research, University of Granada, Avda. Del Conocimiento s/n, 18016 Armilla, Granada, Spain; Instituto de Investigación Biosanitaria IBS.GRANADA, Complejo Hospitalario Universitario de Granada, Granada, 18014, Spain; CIBEROBN (CIBER Physiopathology of Obesity and Nutrition), Instituto de Salud Carlos III, 28029, Madrid, SpainBackground: 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.http://www.sciencedirect.com/science/article/pii/S075333222031310XMetforminMicrobiotaChildren populationPubertal stageObesity |