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Proinflammatory and autoimmunogenic gut microbiome in systemic lupus erythematosus

View ORCID ProfileBei-di Chen, Xin-miao Jia, Jia-yue Xu, Li-dan Zhao, Jun-yi Ji, Bing-xuan Wu, Yun-yun Fei, Hua-xia Yang, Hua Chen, Xiao-xia Zuo, Hui Li, Wen-you Pan, View ORCID ProfileXiao-han Wang, Shuang Ye, Dong-geng Guo, Li Wang, Jing Li, Lin-yi Peng, Wen-jie Zheng, View ORCID ProfileWen Zhang, Feng-chun Zhang, Jian-min Zhang, Wei He, Xue-tao Cao, De-pei Liu, Jun Wang, Xuan Zhang
doi: https://doi.org/10.1101/621995
Bei-di Chen
1Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College Hospital, Beijing, China, 100730
2Clinical Immunology Centre, Medical Epigenetics Research Centre, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 100730
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  • ORCID record for Bei-di Chen
Xin-miao Jia
1Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College Hospital, Beijing, China, 100730
2Clinical Immunology Centre, Medical Epigenetics Research Centre, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 100730
3Central Research Laboratory, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College Hospital, Beijing, China, 100730
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Jia-yue Xu
4CAS Key Laboratory for Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China, 100101
5University of Chinese Academy of Sciences, Beijing, China, 100049
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Li-dan Zhao
1Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College Hospital, Beijing, China, 100730
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Jun-yi Ji
6School of Medicine, Tsinghua University, No.1 Tsinghua Yuan, Beijing, China, 100084
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Bing-xuan Wu
1Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College Hospital, Beijing, China, 100730
2Clinical Immunology Centre, Medical Epigenetics Research Centre, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 100730
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Yun-yun Fei
1Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College Hospital, Beijing, China, 100730
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Hua-xia Yang
1Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College Hospital, Beijing, China, 100730
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Hua Chen
1Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College Hospital, Beijing, China, 100730
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Xiao-xia Zuo
7Department of Rheumatology, Xiangya Hospital, Central South University, Changsha, Hunan, China, 410008
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Hui Li
8Department of Immunology and Rheumatology, Huaian First People’s Hospital, Nanjing Medical University, Huaian, Jiangsu, China, 223300
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Wen-you Pan
8Department of Immunology and Rheumatology, Huaian First People’s Hospital, Nanjing Medical University, Huaian, Jiangsu, China, 223300
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Xiao-han Wang
9Department of Rheumatology, Anyang District Hospital, Anyang, Henan, China, 455002
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Shuang Ye
10Department of Rheumatology, South Campus, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China, 200025
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Dong-geng Guo
11Department of Rheumatology, Ningxia Hui Autonomous Region Peoples Hospital, Affiliated People’s Hospital of Ningxia Medical University, First Affiliated Hospital of Northwest Minzu University, Ningxia Hui Autonomous Region, China, 750000
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Li Wang
1Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College Hospital, Beijing, China, 100730
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Jing Li
1Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College Hospital, Beijing, China, 100730
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Lin-yi Peng
1Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College Hospital, Beijing, China, 100730
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Wen-jie Zheng
1Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College Hospital, Beijing, China, 100730
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Wen Zhang
1Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College Hospital, Beijing, China, 100730
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Feng-chun Zhang
1Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College Hospital, Beijing, China, 100730
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Jian-min Zhang
12Department of Immunology & National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing, China, 100005
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Wei He
12Department of Immunology & National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing, China, 100005
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Xue-tao Cao
12Department of Immunology & National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing, China, 100005
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De-pei Liu
2Clinical Immunology Centre, Medical Epigenetics Research Centre, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 100730
12Department of Immunology & National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing, China, 100005
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Jun Wang
4CAS Key Laboratory for Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China, 100101
5University of Chinese Academy of Sciences, Beijing, China, 100049
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  • For correspondence: zxpumch2003@sina.com junwang@im.ac.cn
Xuan Zhang
1Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College Hospital, Beijing, China, 100730
2Clinical Immunology Centre, Medical Epigenetics Research Centre, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 100730
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  • For correspondence: zxpumch2003@sina.com junwang@im.ac.cn
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Abstract

Systemic lupus erythematosus (SLE), characterized by chronic inflammation and multi-organ damage, has been suggested to associate with gut dysbiosis, but knowledge is limited from small sample size and 16s rRNA-based studies. To shed new light on the role of microbiota in SLE development, we analyzed the fecal metagenome of 117 treatment-naïve SLE patients and 115 sex- and age-matched healthy controls (HC) by deep-sequencing; in addition, 52 of the aforementioned patients have post-treatment fecal metagenome for comparison. We found significant differences in microbial composition and function between SLE and HC, revealing multiple plausible contributing bacterial species and metabolic pathways in SLE. In-depth SNP-based analysis revealed an oral-microbiome origin for two marker species, strengthening the importance of bacterial translocation in disease development. Lastly, we confirmed experimentally that peptides of SLE-enriched species mimicking autoantigens such as Sm and Fas could trigger autoimmune responses, suggesting a potential causal role of gut microbiota in SLE.

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Posted April 29, 2019.
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Proinflammatory and autoimmunogenic gut microbiome in systemic lupus erythematosus
Bei-di Chen, Xin-miao Jia, Jia-yue Xu, Li-dan Zhao, Jun-yi Ji, Bing-xuan Wu, Yun-yun Fei, Hua-xia Yang, Hua Chen, Xiao-xia Zuo, Hui Li, Wen-you Pan, Xiao-han Wang, Shuang Ye, Dong-geng Guo, Li Wang, Jing Li, Lin-yi Peng, Wen-jie Zheng, Wen Zhang, Feng-chun Zhang, Jian-min Zhang, Wei He, Xue-tao Cao, De-pei Liu, Jun Wang, Xuan Zhang
bioRxiv 621995; doi: https://doi.org/10.1101/621995
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Proinflammatory and autoimmunogenic gut microbiome in systemic lupus erythematosus
Bei-di Chen, Xin-miao Jia, Jia-yue Xu, Li-dan Zhao, Jun-yi Ji, Bing-xuan Wu, Yun-yun Fei, Hua-xia Yang, Hua Chen, Xiao-xia Zuo, Hui Li, Wen-you Pan, Xiao-han Wang, Shuang Ye, Dong-geng Guo, Li Wang, Jing Li, Lin-yi Peng, Wen-jie Zheng, Wen Zhang, Feng-chun Zhang, Jian-min Zhang, Wei He, Xue-tao Cao, De-pei Liu, Jun Wang, Xuan Zhang
bioRxiv 621995; doi: https://doi.org/10.1101/621995

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