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29-01-2015 | Microbiome | Article

The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment

Authors:
Xuan Zhang, Dongya Zhang, Huijue Jia, Qiang Feng, Donghui Wang, Di Liang, Xiangni Wu, Junhua Li, Longqin Tang, Yin Li, Zhou Lan, Bing Chen, Yanli Li, Huanzi Zhong, Hailiang Xie, Zhuye Jie, Weineng Chen, Shanmei Tang, Xiaoqiang Xu, Xiaokai Wang, Xianghang Cai, Sheng Liu, Yan Xia, Jiyang Li, Xingye Qiao, Jumana Yousuf Al-Aama, hua Chen, Li Wang, Qing-jun Wu, Fengchun Zhang, Wenjie Zheng, Yongzhe Li, Mingrong Zhang, Guangwen Luo, Wenbin Xue, Liang Xiao, Jun Li, Wanting Chen, Xun Xu, Ye Yin, Huanming Yang, Jian Wang, Karsten Kristiansen, Liang Liu, Ting Li, Qingchun Huang, Yingrui Li, Jun Wang

Abstract

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.

Subject terms: Metagenomics • Rheumatoid arthritis

Nat Med 2015;21:895–905. doi:10.1038/nm.3914

A is an autoimmune disorder affecting tens of millions of people worldwide and is associated with increased mortality owing to cardiovascular and other systemic complications. However, the etiology of RA remains elusive1. Although studies on genetic predisposition to RA have implicated genes such as HLA-DRB1, TNFAIP3, PTPN22 and PADI4, environmental factors have also been shown to contribute to disease pathogenesis1, 2, 3, 4, 5. Microbial triggers have been implicated in RA1; however, the identity and pathogenicity of specific microbes have remained unclear. Although there are reports of clinical success in reducing inflammation in RA with disease-modifying antirheumatic drugs (DMARDs), the development of specific and more effective therapies has been hindered by insufficient understanding of factors that trigger or promote the disease. Investigation of the microbiome might also reveal probiotics that could prevent or attenuate RA symptoms.

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