A high-fiber diet synergizes with Prevotella copri and exacerbates rheumatoid arthritis  

作　　者：Lingjuan Jiang Mengmeng Shang Shengnan Yu Yudong Liu Hui Zhang Yangzhong Zhou Min Wang Tingting Wang Hui Li Zhihua Liu Xuan Zhang 

机构地区：[1]Department of Medical Research Center,National Science and Technology Key Infrastructure on Translational Medicine,Peking Union Medical College Hospital,Department of Rheumatology,Beijing Hospital,National Center of Gerontology,Institute of Geriatric Medicine,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,100730,China [2]State Key Laboratory of Complex Severe and Rare Diseases,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,100730,China [3]Department of Rheumatology,Beijing Hospital,National Center of Gerontology,Institute of Geriatric Medicine,Clinical Immunology Center,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,100730,China [4]Department of Pathology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,100730,China [5]Department of Internal Medicine,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,100730,China [6]Key Laboratory of Infection and Immunity,Institute of Biophysics,Chinese Academy of Sciences,Beijing,100101,China [7]Institute for Immunology,School of Medicine,Tsinghua University,Beijing,100084,China [8]Tsinghua-Peking Center for Life Sciences,Beijing,100084,China

出　　处：《Cellular & Molecular Immunology》2022年第12期1414-1424,共11页中国免疫学杂志（英文版）

基　　金：supported by the National Natural Science Foundation of China (81788101,82230060,81630064,and 81701624);the CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-017,2021-I2M-1-047,2021-I2M-1-040,and 2021-I2M-1-016);the Capital’s Funds for Health Improvement and Research (2020-2-4019);the National Key Research and Development Program of China (Grant no.2018YFE0207300).

摘　　要：Both preclinical and established rheumatoid arthritis(RA)patients display alterations in the gut microbiome.Prevotella spp.are preferentially enriched in a subset of RA patients.Here,we isolated a Prevotella strain,P.copri RA,from the feces of RA patients and showed that colonization of P.copri RA exacerbated arthritis in a collagen-induced arthritis(CIA)model.With the presence of P.copri RA colonization,a high-fiber diet exacerbated arthritis via microbial alterations and intestinal inflammation.Colonization of P.copri together with a high-fiber diet enabled the digestion of complex fiber,which led to the overproduction of organic acids,including fumarate,succinate and short-chain fatty acids.Succinate promoted proinflammatory responses in macrophages,and supplementation with succinate exacerbated arthritis in the CIA model.Our findings highlight the importance of dysbiosis when evaluating the effects of dietary interventions on RA pathogenesis and provide new insight into dietary interventions or microbiome modifications to improve RA management.

关 键 词：Rheumatoid arthritis DYSBIOSIS Prevotella copri High-fber diet Microbiota-derived metabolites 

分 类 号：R593.22[医药卫生—内科学]