Aberrant intestinal microbiota in individuals with prediabetes.

Aberrant intestinal microbiota in individuals with prediabetes.
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DOI:
10.1007/s00125-018-4550-1
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发表时间:
2018-04
期刊:
影响因子:
8.2
通讯作者:
Pedersen O
Pedersen O
中科院分区:
医学1区
文献类型:
--
作者:
Allin KH;Tremaroli V;Caesar R;Jensen BAH;Damgaard MTF;Bahl MI;Licht TR;Hansen TH;Nielsen T;Dantoft TM;Linneberg A;Jørgensen T;Vestergaard H;Kristiansen K;Franks PW;IMI-DIRECT consortium;Hansen T;Bäckhed F;Pedersen O

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2型糖尿病患者的肠道微生物区系异常。然而,最近的研究表明,二甲双胍改变了肠道微生物区系的组成和功能潜力,从而干扰了糖尿病相关微生物的特征。我们测试了特定的肠道微生物区系特征是否与糖尿病前期(定义为空腹血糖为6.1-7.0mmoL/L或HbA1c为42-48mmoL/moL[6.0-6.5%])和一系列代谢健康不良的临床生物标记物有关。在目前的病例对照研究中,我们分析了134名患有糖尿病前期、超重、胰岛素抵抗、血脂异常和低度炎症的丹麦成年人以及134名年龄和性别匹配、糖调节正常的人的肠道微生物区系。我们发现糖尿病前期患者和正常血糖患者之间存在5个细菌属和36个操作分类单位(OTU)的差异。在属水平上,梭状芽孢杆菌的丰度降低(平均log2倍变化−为0.64(SEM0.23),PADJ = 为0.0497),而DOREA、[瘤胃球菌]、链球菌和链球菌的丰度增加(平均log2倍变化为0.51(SEM0.12),PADJ = 5 × 10−4;0.51(SEM0.11),PADJ = 1 × 10−4;0.60(SEM0.21),PADJ = 0.0497;和0.92(SEM0.21),PADJ = 4 × 10−4)。两种OTU差异最大的是梭状芽胞杆菌目(OTU 146564)和粘液阿克曼氏菌,它们在糖尿病前期个体中的丰度都较低(平均对数2倍变化−1.74(SEM0.41),PADJ = 2 × 10−3和−1.65(SEM0.34),PADJ = 4 × 10−4)。从患有糖尿病前期或筛查发现的药物未成熟的2型糖尿病捐赠者的粪便转移到无菌的瑞士Webster或传统的C57BL/6 JJ小鼠身上,并不会导致受体小鼠的血糖调节受损。总体而言,我们的数据显示,糖尿病前期患者具有异常的肠道微生物区系,其特征是梭状芽胞杆菌属和粘液降解细菌粘液降解细菌的丰度降低。我们的发现与对以低度炎症为特征的显性慢性疾病的观察结果相当。这篇文章的在线版本(10.1007/s00125-0184550-1)包含经同行审查但未经编辑的补充材料,授权用户可以使用。
Individuals with type 2 diabetes have aberrant intestinal microbiota. However, recent studies suggest that metformin alters the composition and functional potential of gut microbiota, thereby interfering with the diabetes-related microbial signatures. We tested whether specific gut microbiota profiles are associated with prediabetes (defined as fasting plasma glucose of 6.1–7.0 mmol/l or HbA1c of 42–48 mmol/mol [6.0–6.5%]) and a range of clinical biomarkers of poor metabolic health. In the present case–control study, we analysed the gut microbiota of 134 Danish adults with prediabetes, overweight, insulin resistance, dyslipidaemia and low-grade inflammation and 134 age- and sex-matched individuals with normal glucose regulation. We found that five bacterial genera and 36 operational taxonomic units (OTUs) were differentially abundant between individuals with prediabetes and those with normal glucose regulation. At the genus level, the abundance of Clostridium was decreased (mean log2 fold change −0.64 (SEM 0.23), padj = 0.0497), whereas the abundances of Dorea, [Ruminococcus], Sutterella and Streptococcus were increased (mean log2 fold change 0.51 (SEM 0.12), padj = 5 × 10−4; 0.51 (SEM 0.11), padj = 1 × 10−4; 0.60 (SEM 0.21), padj = 0.0497; and 0.92 (SEM 0.21), padj = 4 × 10−4, respectively). The two OTUs that differed the most were a member of the order Clostridiales (OTU 146564) and Akkermansia muciniphila, which both displayed lower abundance among individuals with prediabetes (mean log2 fold change −1.74 (SEM 0.41), padj = 2 × 10−3 and −1.65 (SEM 0.34), padj = 4 × 10−4, respectively). Faecal transfer from donors with prediabetes or screen-detected, drug-naive type 2 diabetes to germfree Swiss Webster or conventional C57BL/6 J mice did not induce impaired glucose regulation in recipient mice. Collectively, our data show that individuals with prediabetes have aberrant intestinal microbiota characterised by a decreased abundance of the genus Clostridium and the mucin-degrading bacterium A. muciniphila. Our findings are comparable to observations in overt chronic diseases characterised by low-grade inflammation. The online version of this article (10.1007/s00125-018-4550-1) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
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