Chen Zhou1, Hui Zhao2, Xin-Yue Xiao1, Bei-di Chen1, Rui-Jin Guo2, Qi Wang2, Hua Chen3, Li-Dan Zhao1, Chen-Chen Zhang2, Yu-Hao Jiao1, Yan-Mei Ju2, Hua-Xia Yang3, Yun-Yun Fei3, Li Wang3, Min Shen3, Hui Li4, Xiao-Han Wang5, Xin Lu6, Bo Yang6, Jin-Jing Liu3, Jing Li3, Lin-Yi Peng3, Wen-Jie Zheng3, Chun-Yan Zhang3, Jia-Xin Zhou3, Qing-Jun Wu3, Yun-Jiao Yang3, Jin-Mei Su3, Qun Shi3, Di Wu3, Wen Zhang3, Feng-Chun Zhang3, Hui-Jue Jia2, De-Pei Liu7, Zhu-Ye Jie8, Xuan Zhang9. 1. Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, The Ministry of Education Key Laboratory, Beijing, 100730, China; Clinical Immunology Centre, Medical Epigenetics Research Centre, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China. 2. BGI-Shenzhen, Shenzhen, 518083, China. 3. Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, The Ministry of Education Key Laboratory, Beijing, 100730, China. 4. Department of Immunology and Rheumatology, Huaian No.1 People's Hospital, Nanjing Medical University, Huaian, Jiangsu, 223300, China. 5. Department of Rheumatology, Anyang District Hospital, Anyang, Henan, 455002, China. 6. Department of Orthopedics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China. 7. State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China. 8. BGI-Shenzhen, Shenzhen, 518083, China. Electronic address: jiezhuye@genomics.cn. 9. Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, The Ministry of Education Key Laboratory, Beijing, 100730, China; Clinical Immunology Centre, Medical Epigenetics Research Centre, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China. Electronic address: zxpumch2003@sina.com.
Abstract
OBJECTIVE: Gut dysbiosis has been reported implicated in ankylosing spondylitis (AS), a common chronic inflammatory disease mainly affects sacroiliac joints and spine. Utilizing deep sequencing on the feces of untreated AS patients, our study aimed at providing an in-depth understanding of AS gut microbiota. METHODS: We analyzed the fecal metagenome of 85 untreated AS patients and 62 healthy controls by metagenomic shotgun sequencing, and 23 post-treatment feces of those AS patients were collected for comparison. Comparative analyses among different cohorts including AS, rheumatoid arthritis and Behcet's disease were performed to uncover some common signatures related to inflammatory arthritis. Molecular mimicry of a microbial peptide was also demonstrated by ELISpot assay. RESULTS: We identified AS-enriched species including Bacteroides coprophilus, Parabacteroides distasonis, Eubacterium siraeum, Acidaminococcus fermentans and Prevotella copri. Pathway analysis revealed increased oxidative phosphorylation, lipopolysaccharide biosynthesis and glycosaminoglycan degradation in AS gut microbiota. Microbial signatures of AS gut selected by random forest model showed high distinguishing accuracy. Some common signatures related to autoimmunity, such as Bacteroides fragilis and type III secretion system (T3SS), were also found. Finally, in vitro experiments demonstrated an increased amount of IFN-γ producing cells triggered by a bacterial peptide of AS-enriched species, mimicking type II collagen. CONCLUSIONS: These findings collectively indicate that gut microbiota was perturbed in untreated AS patients with diagnostic potential, and some AS-enriched species might be triggers of autoimmunity by molecular mimicry. Additionally, different inflammatory arthritis shared some common microbial signatures.
OBJECTIVE: Gut dysbiosis has been reported implicated in ankylosing spondylitis (AS), a common chronic inflammatory disease mainly affects sacroiliac joints and spine. Utilizing deep sequencing on the feces of untreated AS patients, our study aimed at providing an in-depth understanding of AS gut microbiota. METHODS: We analyzed the fecal metagenome of 85 untreated AS patients and 62 healthy controls by metagenomic shotgun sequencing, and 23 post-treatment feces of those AS patients were collected for comparison. Comparative analyses among different cohorts including AS, rheumatoid arthritis and Behcet's disease were performed to uncover some common signatures related to inflammatory arthritis. Molecular mimicry of a microbial peptide was also demonstrated by ELISpot assay. RESULTS: We identified AS-enriched species including Bacteroides coprophilus, Parabacteroides distasonis, Eubacterium siraeum, Acidaminococcus fermentans and Prevotella copri. Pathway analysis revealed increased oxidative phosphorylation, lipopolysaccharide biosynthesis and glycosaminoglycan degradation in AS gut microbiota. Microbial signatures of AS gut selected by random forest model showed high distinguishing accuracy. Some common signatures related to autoimmunity, such as Bacteroides fragilis and type III secretion system (T3SS), were also found. Finally, in vitro experiments demonstrated an increased amount of IFN-γ producing cells triggered by a bacterial peptide of AS-enriched species, mimicking type II collagen. CONCLUSIONS: These findings collectively indicate that gut microbiota was perturbed in untreated AS patients with diagnostic potential, and some AS-enriched species might be triggers of autoimmunity by molecular mimicry. Additionally, different inflammatory arthritis shared some common microbial signatures.
Authors: Henry Yue Hong Meng; Christopher Chi Hang Mak; Wing Yan Mak; Tao Zuo; Ho Ko; Francis Ka Leung Chan Journal: Eur J Nutr Date: 2022-01-10 Impact factor: 5.614
Authors: Marta Calatayud Arroyo; Tom Van de Wiele; Annelore Beterams; Kim De Paepe; Ann-Sophie De Craemer; Dirk Elewaut; Koen Venken Journal: Sci Rep Date: 2022-06-21 Impact factor: 4.996
Authors: Jessica C Ezeji; Daven K Sarikonda; Austin Hopperton; Hailey L Erkkila; Daniel E Cohen; Sandra P Martinez; Fabio Cominelli; Tomomi Kuwahara; Armand E K Dichosa; Caryn E Good; Michael R Jacobs; Mikhail Khoretonenko; Alida Veloo; Alexander Rodriguez-Palacios Journal: Gut Microbes Date: 2021 Jan-Dec