An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis.
An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis.
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DOI：
10.1186/s13073-016-0299-7
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发表时间：
2016-04-21
期刊：
影响因子：
12.3
通讯作者：
Taneja V
中科院分区：
文献类型：
--
作者：
Chen J;Wright K;Davis JM;Jeraldo P;Marietta EV;Murray J;Nelson H;Matteson EL;Taneja V
类风湿性关节炎（RA）的适应性免疫反应受到宿主遗传学和环境（特别是宿主微生物组）之间相互作用的影响。已经报道了肠道微生物群与各种疾病的关联，尽管影响导致疾病的宿主反应的微生物群的特定组分仍然未知。然而，关于肠道微生物群在RA中的作用的信息有限。在这项研究中，我们的目的是确定一个微生物和代谢产物的档案，可以预测疾病的状态。此外，我们的目的是产生一个人源化的关节炎模型，以确认RA相关的微生物。为了鉴定RA生物标志物谱，对来自RA患者、一级亲属（排除环境/背景作为混杂因素）和随机健康非RA对照的粪便样品的16 S核糖体DNA进行测序。分析代谢产物及其与特定类群的关联，以研究潜在的机制联系。使用人上皮细胞系和人源化关节炎小鼠模型证实了RA相关微生物的作用。与对照组相比，RA患者的肠道微生物多样性降低，这与疾病持续时间和自身抗体水平相关。分类单元水平的分析表明，与对照组相比，RA患者中稀有分类单元（放线菌）的数量有所增加，而丰富的分类单元却有所减少。随机森林算法的基础上的预测模型表明，三个属，柯林斯，Eggerthella，和粪杆菌，与RA分离。科林氏菌的丰度与高水平的α-氨基己二酸和天冬酰胺以及促炎细胞因子IL-17 A的产生密切相关。在实验性关节炎中证实了Collinsella在改变肠道通透性和疾病严重程度方面的作用。这些观察结果表明，RA患者中的生态失调是由某些罕见细菌谱系的丰度引起的。肠道微生物群和代谢特征之间的相关性可以确定疾病病因和进展的预测特征。本文的在线版本（doi：10.1186/s13073-016-0299-7）包含补充材料，可供授权用户使用。
The adaptive immune response in rheumatoid arthritis (RA) is influenced by an interaction between host genetics and environment, particularly the host microbiome. Association of the gut microbiota with various diseases has been reported, though the specific components of the microbiota that affect the host response leading to disease remain unknown. However, there is limited information on the role of gut microbiota in RA. In this study we aimed to define a microbial and metabolite profile that could predict disease status. In addition, we aimed to generate a humanized model of arthritis to confirm the RA-associated microbe. To identify an RA biomarker profile, the 16S ribosomal DNA of fecal samples from RA patients, first-degree relatives (to rule out environment/background as confounding factors), and random healthy non-RA controls were sequenced. Analysis of metabolites and their association with specific taxa was performed to investigate a potential mechanistic link. The role of an RA-associated microbe was confirmed using a human epithelial cell line and a humanized mouse model of arthritis. Patients with RA exhibited decreased gut microbial diversity compared with controls, which correlated with disease duration and autoantibody levels. A taxon-level analysis suggested an expansion of rare taxa, Actinobacteria, with a decrease in abundant taxa in patients with RA compared with controls. Prediction models based on the random forests algorithm suggested that three genera, Collinsella, Eggerthella, and Faecalibacterium, segregated with RA. The abundance of Collinsella correlated strongly with high levels of alpha-aminoadipic acid and asparagine as well as production of the proinflammatory cytokine IL-17A. A role for Collinsella in altering gut permeability and disease severity was confirmed in experimental arthritis. These observations suggest dysbiosis in RA patients resulting from the abundance of certain rare bacterial lineages. A correlation between the intestinal microbiota and metabolic signatures could determine a predictive profile for disease causation and progression. The online version of this article (doi:10.1186/s13073-016-0299-7) contains supplementary material, which is available to authorized users.