Individuals at risk for rheumatoid arthritis harbor differential intestinal bacteriophage communities with distinct metabolic potential

Cell Host Microbe. 2021 May 12;29(5):726-739.e5. doi: 10.1016/j.chom.2021.03.020. Epub 2021 May 5.


Rheumatoid arthritis (RA) is an autoimmune disease characterized in seropositive individuals by the presence of anti-cyclic citrullinated protein (CCP) antibodies. RA is linked to the intestinal microbiota, yet the association of microbes with CCP serology and their contribution to RA is unclear. We describe intestinal phage communities of individuals at risk for developing RA, with or without anti-CCP antibodies, whose first-degree relatives have been diagnosed with RA. We show that at-risk individuals harbor intestinal phage compositions that diverge based on CCP serology, are dominated by Streptococcaceae, Bacteroidaceae, and Lachnospiraceae phages, and may originate from disparate ecosystems. These phages encode unique repertoires of auxiliary metabolic genes, which associate with anti-CCP status, suggesting that these phages directly influence the metabolic and immunomodulatory capability of the microbiota. This work sets the stage for the use of phages as preclinical biomarkers and provides insight into a possible microbial-based causation of RA disease development.

Keywords: autoimmune disease; bacteriophages; microbiome; phage-host interaction; phage-host metabolism; rheumatoid arthritis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Citrullinated Protein Antibodies / blood
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / virology*
  • Bacteriophages / classification
  • Bacteriophages / genetics
  • Bacteriophages / isolation & purification*
  • Female
  • Humans
  • Intestines / virology*
  • Male
  • Microbiota
  • Middle Aged
  • Phylogeny
  • Risk Factors


  • Anti-Citrullinated Protein Antibodies