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

• Published in: Cell host & microbe Vol. 29; no. 5; pp. 726 - 739.e5
• Main Authors: Mangalea, Mihnea R., Paez-Espino, David, Kieft, Kristopher, Chatterjee, Anushila, Chriswell, Meagan E., Seifert, Jennifer A., Feser, Marie L., Demoruelle, M. Kristen, Sakatos, Alexandra, Anantharaman, Karthik, Deane, Kevin D., Kuhn, Kristine A., Holers, V. Michael, Duerkop, Breck A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.05.2021
• Subjects: Adult; Aged; Anti-Citrullinated Protein Antibodies - blood; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - metabolism; Arthritis, Rheumatoid - virology; autoimmune disease; bacteriophages; Bacteriophages - classification; Bacteriophages - genetics; Bacteriophages - isolation & purification; Female; Humans; Intestines - virology; Male; microbiome; Microbiota; Middle Aged; phage-host interaction; phage-host metabolism; Phylogeny; rheumatoid arthritis; Risk Factors; phage-host interaction; rheumatoid arthritis; autoimmune disease; microbiome; phage-host metabolism; bacteriophages
• ISSN: 1931-3128; 1934-6069
• DOI: 10.1016/j.chom.2021.03.020

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. [Display omitted] •Unique intestinal phage compositions correlate to at-risk RA anti-CCP serology•Lachnospiraceae phage-host interactions dominate in CCP+ individuals at risk for RA•Phages from CCP+ individuals may originate from disparate ecological niches•Phage AMGs contribute to cohort-associated differences Mangalea et al. characterize intestinal bacteriophage communities from humans at risk of developing rheumatoid arthritis. Bacteriophage profiles diverge based on anti-cyclic citrullinated protein autoantibody status compared to healthy controls. Bacteriophage profiling could complement existing diagnostics as a microbial biomarker for preclinical rheumatoid arthritis.