Intestinal VLP reads and predicted phage contigs for at-risk RA individuals

Here, we describe the intestinal phage communities of individuals at risk for developing rheumatoid arthritis (RA), with or without anti-CCP antibodies, compared to healthy adults with no family history of RA. We show that these at-risk individuals harbor distinct intestinal phage communities that diverge based on CCP serology. Using short read shotgun metagenomics, we describe an RA-related intestinal virome in which Lachnospiraceae-targeting phages dominate. We further describe a dysbiotic community of phages in CCP positive individuals that originate from disparate ecosystems compared to healthy controls or CCP negative individuals. Phages that are differentially abundant compared to healthy controls encode a unique repertoire of auxiliary metabolic genes (AMGs) which associate with anti-CCP status, suggesting that disparate phages directly influence the metabolism of the intestinal microbiota and its immunomodulatory capability. This work sets the stage for using phages and their genetic features as preclinical biomarkers of RA and provides insight into a microbial-based causation of RA disease development.