Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
1] BGI-Shenzhen, Shenzhen, China. [2] Shenzhen Key Laboratory of Human Commensal Microorganisms and Health Research, BGI-Shenzhen, Shenzhen, China.
Nat Med. 2015 Aug;21(8):895-905. doi: 10.1038/nm.3914. Epub 2015 Jul 27.
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.
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法测序和宏基因组关联研究（MGWAS）。肠道和口腔微生物组之间存在一致性，表明不同身体部位的物种丰度和功能存在重叠。在 RA 患者的肠道和口腔微生物组中检测到了失调，但在 RA 治疗后部分得到了缓解。肠道、牙齿或唾液微生物组的改变可以将 RA 患者与健康对照者区分开来，与临床指标相关，并且可以基于对治疗的反应对个体进行分层。特别是，在所有三个部位，嗜血菌属在 RA 患者中均减少，并且与血清自身抗体水平呈负相关，而唾液乳杆菌在所有三个部位的 RA 患者中均过度表达，并且在非常活跃的 RA 病例中数量增加。在功能上，RA 患者的微生物组中，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 RA 相关的人类抗原的分子模拟也可以检测到。我们的研究结果确立了 RA 患者肠道和口腔微生物组的特定改变，并提出了利用微生物组组成进行预后和诊断的潜在方法。
