Metformin induces weight loss associated with gut microbiota alteration in non-diabetic obese women: a randomized double-blind clinical trial
Metformin induces weight loss associated with gut microbiota alteration in non-diabetic obese women: a randomized double-blind clinical trial
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DOI：
10.1530/eje-18-0826
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发表时间：
2019-03-01
影响因子：
5.8
通讯作者：
Larijani, Bagher
中科院分区：
文献类型：
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作者：
Ejtahed, Hanieh-Sadat;Tito, Raul Y.;Larijani, Bagher
目的：过去几十年来，肥胖症的流行率不断上升，构成了全球健康挑战。药物治疗建议伴随着生活方式的改变肥胖管理。在这里，我们进行了一项临床试验，以调查二甲双胍对人体测量指标和肠道菌群组成的影响，在非糖尿病，治疗初治的肥胖妇女与低热量饮食（LCD）。设计：随机双盲平行组临床trailMethods：46名肥胖妇女被随机分配到二甲双胍（500毫克/片）或安慰剂组使用计算机生成的随机数字。两组受试者每天服用两片，持续2个月。在基线和试验结束时进行人体测量以及血液和粪便样本的采集。肠道菌群组成进行了评估，使用16 S rRNA扩增sequencing.Results：24和22名受试者被纳入二甲双胍+ LCD和安慰剂+ LCD组，分别在试验结束时，20和16名受试者进行了分析。二甲双胍+ LCD和安慰剂+ LCD分别使BMI较基线值降低4.5%和2.6%（P < 0.01）。二甲双胍+ LCD组胰岛素浓度降低（P = 0.046）。二甲双胍+ LCD组的总体粪便微生物群组成和多样性未受影响。然而，二甲双胍+ LCD干预后，观察到大肠杆菌/志贺菌丰度显著增加（P = 0.026）。安慰剂+ LCD组的粪便乙酸盐浓度（但不是生产者）显著更高，校正基线值和BMI（P = 0.002）。结论：尽管二甲双胍摄入后体重减轻，但肥胖女性的总体粪便微生物群组成基本保持不变，特定变形菌群的变化除外。
Objective: The increasing prevalence of obesity over the past few decades constitutes a global health challenge. Pharmacological therapy is recommended to accompany life-style modification for obesity management. Here, we perform a clinical trial to investigate the effects of metformin on anthropometric indices and gut microbiota composition in non-diabetic, treatment-naive obese women with a low-calorie diet (LCD).Design: Randomized double-blind parallel-group clinical trailMethods: Forty-six obese women were randomly assigned to the metformin (500 mg/tab) or placebo groups using computer-generated random numbers. Subjects in both groups took two tablets per day for 2 months. Anthropometric measurements and collection of blood and fecal samples were done at the baseline and at the end of the trial. Gut microbiota composition was assessed using 16S rRNA amplicon sequencing.Results: Twenty-four and twenty-two subjects were included in the metformin + LCD and placebo + LCD groups, respectively; at the end of trial, 20 and 16 subjects were analyzed. The metformin + LCD and placebo + LCD caused a 4.5 and 2.6% decrease in BMI from the baseline values, respectively (P < 0.01). Insulin concentration decreased in the metformin + LCD group (P = 0.046). The overall fecal microbiota composition and diversity were unaffected in the metformin + LCD group. However, a significant specific increase in Escherichia/Shigello abundance was observed after metformin + LCD intervention (P = 0.026). Fecal acetate concentration, but not producers, was significantly higher in the placebo + LCD group, adjusted for baseline values and BMI (P = 0.002).Conclusions: Despite the weight reduction after metformin intake, the overall fecal microbiota composition remained largely unchanged in obese women, with exception of changes in specific proteobacterial groups.