Metformin Is Associated With Higher Relative Abundance of Mucin-Degrading Akkermansia muciniphila and Several Short-Chain Fatty Acid-Producing Microbiota in the Gut

Metformin Is Associated With Higher Relative Abundance of Mucin-Degrading Akkermansia muciniphila and Several Short-Chain Fatty Acid-Producing Microbiota in the Gut
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DOI:
10.2337/dc16-1324
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发表时间:
2017-01-01
期刊:
影响因子:
16.2
通讯作者:
Escobar, Juan S.
Escobar, Juan S.
中科院分区:
医学1区
文献类型:
--
作者:
de la Cuesta-Zuluaga, Jacobo;Mueller, Noel T.;Escobar, Juan S.

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最近的研究表明,二甲双胍对葡萄糖代谢的有益作用可能是微生物介导的。我们研究了社区居住的哥伦比亚成年人中2型糖尿病,二甲双胍和肠道微生物群的关系。在以前的研究的基础上,我们假设二甲双胍与更高水平的短链脂肪酸(SCFA)生产和粘蛋白降解microbiota.RESEARCH设计和方法参与者是从一个更大的队列中选择的459名参与者。目前的分析集中在28名被诊断为糖尿病的参与者-14名服用二甲双胍-和84名无糖尿病的参与者,他们与糖尿病参与者的性别,年龄和BMI匹配(3比1)。我们测量了人口统计学信息,人体测量学和血液生化参数,并收集了粪便样本,从中我们进行了16 S rRNA基因测序,以分析肠道微生物群的组成和结构。与未患糖尿病的参与者相比,服用二甲双胍的糖尿病参与者具有较高的嗜粘蛋白阿克曼氏菌相对丰度,这是一种已知用于粘蛋白降解的微生物群,以及几种已知用于产生SCFA的肠道微生物群,包括丁酸弧菌、两歧双歧杆菌、巨球菌和普雷沃氏菌的操作分类单位。相比之下,与无糖尿病的参与者相比,未服用二甲双胍的糖尿病参与者具有较高的梭菌科02 d 06相对丰度和普雷沃氏菌属的独特操作分类单位,以及较低丰度的粪黄肠球菌。嗜粘蛋白菌以及几种产生SCFA的微生物群。未来的研究需要确定这些变化是否介导二甲双胍的血糖和抗炎特性。
OBJECTIVERecent studies suggest the beneficial effects of metformin on glucose metabolism may be microbially mediated. We examined the association of type 2 diabetes, metformin, and gut microbiota in community-dwelling Colombian adults. On the basis of previous research, we hypothesized that metformin is associated with higher levels of short-chain fatty acid (SCFA)-producing and mucin-degrading microbiota.RESEARCH DESIGN AND METHODSParticipants were selected from a larger cohort of 459 participants. The present analyses focus on the 28 participants diagnosed with diabetes-14 taking metformin- and the 84 participants without diabetes who were matched (3-to-1) to participants with diabetes by sex, age, and BMI. We measured demographic information, anthropometry, and blood biochemical parameters and collected fecal samples from which we performed 16S rRNA gene sequencing to analyze the composition and structure of the gut microbiota.RESULTSWe found an association between diabetes and gut microbiota that was modified by metformin use. Compared with participants without diabetes, participants with diabetes taking metformin had higher relative abundance of Akkermansia muciniphila, a microbiota known for mucin degradation, and several gut microbiota known for production of SCFAs, including Butyrivibrio, Bifidobacterium bifidum, Megasphaera, and an operational taxonomic unit of Prevotella. In contrast, compared with participants without diabetes, participants with diabetes not taking metformin had higher relative abundance of Clostridiaceae 02d06 and a distinct operational taxonomic unit of Prevotella and a lower abundance of Enterococcus casseliflavus.CONCLUSIONSOur results support the hypothesis that metformin shifts gut microbiota composition through the enrichment of mucin-degrading A. muciniphila as well as several SCFA-producing microbiota. Future studies are needed to determine if these shifts mediate metformin's glycemic and anti-inflammatory properties.