Metformin Affects Gut Microbiome Composition and Function and Circulating Short-Chain Fatty Acids: A Randomized Trial.
Metformin Affects Gut Microbiome Composition and Function and Circulating Short-Chain Fatty Acids: A Randomized Trial.
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DOI：
10.2337/dc20-2257
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发表时间：
2021-07
期刊：
影响因子：
16.2
通讯作者：
Yeh HC
中科院分区：
文献类型：
--
作者：
Mueller NT;Differding MK;Zhang M;Maruthur NM;Juraschek SP;Miller ER 3rd;Appel LJ;Yeh HC
确定二甲双胍治疗和行为减肥对肠道菌群和短链脂肪酸（SCFA）的长期影响。我们进行了一项3平行组随机试验。我们招募了超重/肥胖的成年人，他们曾接受过实体瘤治疗，但没有正在进行的癌症治疗，并将他们（n = 121）随机分为1）二甲双胍（高达2,000 mg），2）教练指导的行为减肥，或3）自我指导的护理（对照）12个月。我们在基线（n = 114）、6个月（n = 109）和12个月（n = 105）时收集粪便和血清。从粪便中提取微生物DNA，进行扩增子和宏基因组测序。我们从空腹血清中检测SCFAs和其他生化参数。在121名参与者中，79%是女性，46%是黑人，平均年龄为60岁。只有二甲双胍治疗显著改变了微生物群组成。与对照组相比，二甲双胍处理增加了埃希氏菌（通过宏基因组测序确认为大肠埃希氏菌）和扭体瘤胃球菌的扩增子序列变体，减少了6个月和12个月时的巴氏肠杆菌，并减少了罗斯拜瑞氏菌属，包括罗斯拜瑞氏菌。faecis和R. 12个月大的时候，二甲双胍组与行为减肥组的效果相似。与对照组相比，二甲双胍在6个月时也增加了丁酸盐、乙酸盐和戊酸盐（但在12个月时没有）。与对照组相比，行为体重减轻并没有显著改变微生物群组成，但在6个月时增加了乙酸盐（但在12个月时没有）。醋酸盐升高与空腹胰岛素降低相关。对二甲双胍组的一个子集进行的额外的全基因组宏基因组测序显示，二甲双胍改变了62个宏基因组功能途径，包括一个乙酸产生途径和三个葡萄糖代谢途径。代谢物，而不是行为减肥，在6个月和12个月时影响肠道微生物群组成。二甲双胍和行为体重减轻都改变了6个月时的循环SCFA，包括增加醋酸盐，这与较低的空腹胰岛素相关。未来的研究需要阐明肠道微生物是否介导或改变二甲双胍的健康效应。
To determine the longer-term effects of metformin treatment and behavioral weight loss on gut microbiota and short-chain fatty acids (SCFAs). We conducted a 3-parallel-arm, randomized trial. We enrolled overweight/obese adults who had been treated for solid tumors but had no ongoing cancer treatment and randomized them (n = 121) to either 1) metformin (up to 2,000 mg), 2) coach-directed behavioral weight loss, or 3) self-directed care (control) for 12 months. We collected stool and serum at baseline (n = 114), 6 months (n = 109), and 12 months (n = 105). From stool, we extracted microbial DNA and conducted amplicon and metagenomic sequencing. We measured SCFAs and other biochemical parameters from fasting serum. Of the 121 participants, 79% were female and 46% were Black, and the mean age was 60 years. Only metformin treatment significantly altered microbiota composition. Compared with control, metformin treatment increased amplicon sequence variants for Escherichia (confirmed as Escherichia coli by metagenomic sequencing) and Ruminococcus torques and decreased Intestinibacter bartlettii at both 6 and 12 months and decreased the genus Roseburia, including R. faecis and R. intestinalis, at 12 months. Effects were similar in comparison of the metformin group with the behavioral weight loss group. Metformin versus control also increased butyrate, acetate, and valerate at 6 months (but not at 12 months). Behavioral weight loss versus control did not significantly alter microbiota composition but did increase acetate at 6 months (but not at 12 months). Increases in acetate were associated with decreases in fasting insulin. Additional whole-genome metagenomic sequencing of a subset of the metformin group showed that metformin altered 62 metagenomic functional pathways, including an acetate-producing pathway and three pathways in glucose metabolism. Metformin, but not behavioral weight loss, impacted gut microbiota composition at 6 months and 12 months. Both metformin and behavioral weight loss altered circulating SCFAs at 6 months, including increasing acetate, which correlated with lower fasting insulin. Future research is needed to elucidate whether the gut microboime mediates or modifies metformin’s health effects.
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影响因子：
4.6
作者：
Choo JM;Leong LE;Rogers GB
通讯作者：
Rogers GB
影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP
影响因子：
8.2
作者：
Bryrup, Thomas;Thomsen, Caecilie W.;Nielsen, Trine
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Nielsen, Trine
影响因子：
15.5
作者：
Fernandes AD;Reid JN;Macklaim JM;McMurrough TA;Edgell DR;Gloor GB
通讯作者：
Gloor GB
影响因子：
2.3
作者：
BONORA, E;CIGOLINI, M;BUTTURINI, U
通讯作者：
BUTTURINI, U