Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis
Jose U Scher,
Andrew Sczesnak,
Randy S Longman,
Nicola Segata,
Carles Ubeda,
Craig Bielski,
Tim Rostron,
Vincenzo Cerundolo,
Eric G Pamer,
Steven B Abramson,
Curtis Huttenhower,
Dan R Littman
Affiliations
Jose U Scher
Department of Medicine, New York University School of Medicine and Hospital for Joint Diseases, New York, United States
Andrew Sczesnak
Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, United States; Graduate Program in Bioinformatics and Computational Biology, University of California, San Francisco, San Francisco, United States
Randy S Longman
Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, United States; Jill Roberts IBD Center, Department of Medicine, Weill Cornell Medical College, New York, United States
Nicola Segata
Centre for Integrative Biology, University of Trento, Trento, Italy; Department of Biostatistics, Harvard School of Public Health, Boston, United States
Carles Ubeda
Immunology Program, Infectious Diseases Service, and The Lucille Castori Center for Microbes, Inflammation, and Cancer, Memorial Sloan-Kettering Cancer Center, New York, United States; Centro Superior de Investigacion en Salud Publica, University of Valencia, Valencia, Spain
Craig Bielski
Department of Biostatistics, Harvard School of Public Health, Boston, United States
Tim Rostron
Department of Medicine, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom
Vincenzo Cerundolo
Department of Medicine, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom
Eric G Pamer
Immunology Program, Infectious Diseases Service, and The Lucille Castori Center for Microbes, Inflammation, and Cancer, Memorial Sloan-Kettering Cancer Center, New York, United States
Steven B Abramson
Department of Medicine, New York University School of Medicine and Hospital for Joint Diseases, New York, United States
Curtis Huttenhower
Department of Biostatistics, Harvard School of Public Health, Boston, United States
Dan R Littman
Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, United States; Howard Hughes Medical Institute, New York University School of Medicine, New York, United States
Rheumatoid arthritis (RA) is a prevalent systemic autoimmune disease, caused by a combination of genetic and environmental factors. Animal models suggest a role for intestinal bacteria in supporting the systemic immune response required for joint inflammation. Here we performed 16S sequencing on 114 stool samples from rheumatoid arthritis patients and controls, and shotgun sequencing on a subset of 44 such samples. We identified the presence of Prevotella copri as strongly correlated with disease in new-onset untreated rheumatoid arthritis (NORA) patients. Increases in Prevotella abundance correlated with a reduction in Bacteroides and a loss of reportedly beneficial microbes in NORA subjects. We also identified unique Prevotella genes that correlated with disease. Further, colonization of mice revealed the ability of P. copri to dominate the intestinal microbiota and resulted in an increased sensitivity to chemically induced colitis. This work identifies a potential role for P. copri in the pathogenesis of RA.
