评估肥胖儿童在接受二甲双胍干预后的肠道微生物群：一项随机对照试验的宏基因组学研究。

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

机构信息

Institute 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.

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.

出版信息

Biomed Pharmacother. 2021 Feb;134:111117. doi: 10.1016/j.biopha.2020.111117. Epub 2020 Dec 24.

DOI:10.1016/j.biopha.2020.111117

PMID:33360047

Abstract

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.

摘要

背景

二甲双胍是一种一线口服抗糖尿病药物，在治疗儿童和青少年肥胖方面已显示出良好的效果，可能会影响肠道微生物群的组成。我们旨在评估肥胖的非糖尿病儿童在接受二甲双胍干预后肠道微生物群是否会发生变化。

方法

本研究是一项多中心、双盲、随机对照临床试验，共纳入 160 例肥胖儿童。儿童被随机分为二甲双胍（1g/天）组或安慰剂组，两组均同时接受健康生活方式建议。然后，我们对 33 名儿童（15 名接受二甲双胍，18 名接受安慰剂）的亚样本进行了宏基因组分析。采用线性混合效应模型（LMM）根据治疗确定从基线到六个月时的丰度变化。为了通过聚类分析数据，我们进行了主成分分析，以了解生活方式习惯是否会根据治疗组的不同而对微生物群产生不同的影响。

结果

与二甲双胍相比，安慰剂治疗后厚壁菌门的丰度更高。然而，时间×治疗的交互作用仅显示出显著趋势（安慰剂治疗后增加 4.6%至 8.1%，二甲双胍治疗后增加 3.8%至 2.6%，p=0.055）。在属水平上，只有在接受安慰剂干预后，芽孢杆菌的丰度显著高于二甲双胍（安慰剂治疗后增加 2.5%至 5.7%，二甲双胍治疗后增加 1.5%至 0.8%，p=0.044）。此外，根据相似的食物消耗，发现了由厚壁菌门、拟杆菌门和疣微菌门组成的不同菌群。