title: The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment.
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.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] Shenzhen Key Laboratory of Human Commensal Microorganisms and Health Research, BGI-Shenzhen, Shenzhen, China.
authors.forename: Dongya
authors.initials: D
authors.lastname: Zhang
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] Shenzhen Key Laboratory of Human Commensal Microorganisms and Health Research, BGI-Shenzhen, Shenzhen, China.
authors.forename: Huijue
authors.identifier: 000000023592126X
authors.initials: H
authors.lastname: Jia
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] Shenzhen Engineering Laboratory of Detection and Intervention of Human Intestinal Microbiome, BGI-Shenzhen, Shenzhen, China. [3] Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Feng
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Donghui
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Di
authors.initials: D
authors.lastname: Liang
authors.affiliation: Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xiangni
authors.initials: X
authors.lastname: Wu
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] Shenzhen Key Laboratory of Human Commensal Microorganisms and Health Research, BGI-Shenzhen, Shenzhen, China. [3] School of Bioscience and Biotechnology, South China University of Technology, Guangzhou, China.
authors.forename: Junhua
authors.initials: J
authors.lastname: Li
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Longqing
authors.initials: L
authors.lastname: Tang
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Li
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Lan
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Li
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Huanzi
authors.initials: H
authors.lastname: Zhong
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Hailiang
authors.initials: H
authors.lastname: Xie
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Zhuye
authors.initials: Z
authors.lastname: Jie
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Weineng
authors.initials: W
authors.lastname: Chen
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Shanmei
authors.initials: S
authors.lastname: Tang
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, China.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Xu
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, China.
authors.forename: Xiaokai
authors.initials: X
authors.lastname: Wang
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Xianghang
authors.initials: X
authors.lastname: Cai
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Liu
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xia
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] Qingdao University-BGI Joint Innovation College, Qingdao University, Qingdao, China.
authors.forename: Jiyang
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Mathematical Sciences, Binghamton University, State University of New York, Binghamton, New York, USA.
authors.forename: Xingye
authors.initials: X
authors.lastname: Qiao
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] Princess Al-Jawhara Al Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Jumana Yousuf
authors.initials: JY
authors.lastname: Al-Aama
authors.affiliation: Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Qing-Jun
authors.initials: QJ
authors.lastname: Wu
authors.affiliation: Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Fengchun
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Yongzhe
authors.initials: Y
authors.lastname: Li
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Mingrong
authors.initials: M
authors.lastname: Zhang
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Guangwen
authors.initials: G
authors.lastname: Luo
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Xue
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] Shenzhen Key Laboratory of Human Commensal Microorganisms and Health Research, BGI-Shenzhen, Shenzhen, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xiao
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Wanting
authors.initials: W
authors.lastname: Chen
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Xu
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yin
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Huanming
authors.initials: H
authors.lastname: Yang
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
authors.affiliation: Macau University of Science and Technology, Taipa, Macau, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.affiliation: Macau University of Science and Technology, Taipa, Macau, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Rheumatology, Guangdong Hospital of Traditional Chinese Medicine, Guangzhou, China.
authors.forename: Qingchun
authors.initials: Q
authors.lastname: Huang
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Yingrui
authors.initials: Y
authors.lastname: Li
authors.affiliation: 1] BGI-Shenzhen, Shenzhen, China. [2] Department of Biology, University of Copenhagen, Copenhagen, Denmark. [3] Macau University of Science and Technology, Taipa, Macau, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000382:microbiology*; D002097:C-Reactive Protein / Q000032:analysis; D006801:Humans; D007422:Intestines / Q000382:microbiology*; D054892:Metagenome; D064307:Microbiota; D009055:Mouth / Q000382:microbiology*; D012463:Saliva / Q000382:microbiology
chemical_list: D018501:Antirheumatic Agents; D002097:C-Reactive Protein