The delayed effects of antibiotics in type 2 diabetes, friend or foe?
The delayed effects of antibiotics in type 2 diabetes, friend or foe?
复制标题
抗生素对 2 型糖尿病的延迟效应是友还是敌？
DOI：
10.1530/joe-17-0709
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发表时间：
2018-08-01
影响因子：
4
通讯作者：
Gu, Yanyun
中科院分区：
文献类型：
--
作者：
Fu, Lihong;Qiu, Yixuan;Gu, Yanyun
越来越多的证据表明，抗生素（abx）在停止使用后对肠道微生物群的延迟效应不如其对宿主代谢的直接效应有利。然而，目前尚不清楚不同的abx依赖性代谢效应如何影响糖尿病受试者以及肠道微生物群如何参与。在这里，我们用abx鸡尾酒治疗db/db小鼠12天，停药24天。我们发现db/db小鼠在abx治疗后表现出体重和血糖下降，在abx停止后迅速赶上。abx停药后24天，db/db小鼠表现出血浆、肝脏总胆固醇（TC）水平和肝脏重量增加。当时的肠道微生物群组成显示脱硫弧菌科和Rikenellaceae的相对丰度（RA）降低，丹毒丝菌科和Mogibacteriaceae的RA增加，这与肠道内容物中短链脂肪酸（SCFA）（如丙酸和戊酸）减少以及粪便牛磺酸结合胆汁酸（BA）水平升高相关。分子生物学研究表明，胆固醇抑制肝脏BA合成，阻碍胆固醇的细胞内转运和胆汁排泄，均导致肝脏TC蓄积。肠道微生物群组成、微生物代谢产物谱和宿主表型的改变之间的关联表明存在肠道微生物群相关机制，其介导abx对db/db小鼠胆固醇代谢的不利延迟效应。因此，我们呼吁在研究微生物-宿主相互作用的糖尿病动物模型和预防慢性心血管后果的2型糖尿病受试者中应用abx时要谨慎。
An increasing amount of evidence suggests that the delayed effect of antibiotics (abx) on gut microbiota after its cessation is not as favorable as its immediate effect on host metabolism. However, it is not known how the diverse abx-dependent metabolic effects influence diabetic subjects and how gut microbiota is involved. Here, we treated db/db mice with abx cocktail for 12 days and discontinued for 24 days. We found that db/db mice showed decreased body weight and blood glucose after abx treatment, which rapidly caught up after abx cessation. Twenty-four days after abx withdrawal, db/db mice exhibit increased plasma, hepatic total cholesterol (TC) levels and liver weight. The gut microbiota composition at that time showed decreased relative abundances (RAs) of Desulfovibrionaceae and Rikenellaceae, increased RA of Erysipelotrichaceae and Mogibacteriaceae, which were correlating with the reduced short-chain fatty acids (SCFAs) in gut content, such as propionic acid and valeric acid and with the elevated fecal taurine-conjugated bile acids (BAs) levels. The molecular biology studies showed inhibited hepatic BA synthesis from cholesterol, impeded intracellular transportation and biliary excretion of cholesterol that all conferred to liver TC accumulation. The associations among alterations of gut microbiota composition, microbial metabolite profiles and host phenotypes suggested the existence of gut microbiota-linked mechanisms that mediate the unfavorable delayed effects of abx on db/db mice cholesterol metabolism. Thus, we call upon the caution of applying abx in diabetic animal models for studying microbiota-host interaction and in type 2 diabetes subjects for preventing chronic cardiovascular consequences.