Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis

Author:

Scher Jose U1,Sczesnak Andrew23,Longman Randy S24,Segata Nicola56,Ubeda Carles78,Bielski Craig6,Rostron Tim9,Cerundolo Vincenzo9,Pamer Eric G7,Abramson Steven B1,Huttenhower Curtis6,Littman Dan R210

Affiliation:

1. Department of Medicine, New York University School of Medicine and Hospital for Joint Diseases, New York, United States

2. Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, United States

3. Graduate Program in Bioinformatics and Computational Biology, University of California, San Francisco, San Francisco, United States

4. Jill Roberts IBD Center, Department of Medicine, Weill Cornell Medical College, New York, United States

5. Centre for Integrative Biology, University of Trento, Trento, Italy

6. Department of Biostatistics, Harvard School of Public Health, Boston, United States

7. Immunology Program, Infectious Diseases Service, and The Lucille Castori Center for Microbes, Inflammation, and Cancer, Memorial Sloan-Kettering Cancer Center, New York, United States

8. Centro Superior de Investigacion en Salud Publica, University of Valencia, Valencia, Spain

9. Department of Medicine, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom

10. Howard Hughes Medical Institute, New York University School of Medicine, New York, United States

Abstract

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.

Funder

National Institutes of Health

Howard Hughes Medical Institute

American Gastroenterological Association

NSF Graduate Research Fellowship

Danone Research

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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