The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment
The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment
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DOI：
10.1038/nm.3914
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发表时间：
2015-08-01
期刊：
影响因子：
82.9
通讯作者：
Wang, Jun
中科院分区：
文献类型：
--
作者：
Zhang, Xuan;Zhang, Dongya;Wang, Jun
我们对类风湿关节炎（RA）患者和健康对照者的粪便、牙齿和唾液样本进行了宏基因组鸟枪测序和全宏基因组关联研究（MGWAS）。在肠道和口腔微生物组之间观察到一致性，表明物种在不同身体部位的丰度和功能重叠。在RA患者的肠道和口腔微生物组中检测到生态失调，但在RA治疗后部分解决。肠道、牙齿或唾液微生物组的改变将RA患者与健康对照组区分开来，与临床措施相关，可用于根据患者对治疗的反应对患者进行分层。特别是，血友菌在RA患者的所有三个位点都减少了，并且与血清自身抗体水平呈负相关，而唾液乳杆菌在RA患者的所有三个位点都过量存在，并且在非常活跃的RA患者中数量增加。在功能上，RA患者的微生物群中铁、硫、锌和精氨酸的氧化还原环境、运输和代谢发生了改变。与类风湿关节炎相关的人抗原的分子模拟也被检测到。我们的研究结果确定了RA患者肠道和口腔微生物组的特异性改变，并提出了使用微生物组组成进行预后和诊断的潜在方法。
We carried out metagenomic shotgun sequencing and a metagenome-wide association study (MGWAS) of fecal, dental and salivary samples from a cohort of individuals with rheumatoid arthritis (RA) and healthy controls. Concordance was observed between the gut and oral microbiomes, suggesting overlap in the abundance and function of species at different body sites. Dysbiosis was detected in the gut and oral microbiomes of RA patients, but it was partially resolved after RA treatment. Alterations in the gut, dental or saliva microbiome distinguished individuals with RA from healthy controls, were correlated with clinical measures and could be used to stratify individuals on the basis of their response to therapy. In particular, Haemophilus spp. were depleted in individuals with RA at all three sites and negatively correlated with levels of serum autoantibodies, whereas Lactobacillus salivarius was over-represented in individuals with RA at all three sites and was present in increased amounts in cases of very active RA. Functionally, the redox environment, transport and metabolism of iron, sulfur, zinc and arginine were altered in the microbiota of individuals with RA. Molecular mimicry of human antigens related to RA was also detectable. Our results establish specific alterations in the gut and oral microbiomes in individuals with RA and suggest potential ways of using microbiome composition for prognosis and diagnosis.