Study Links Gut Microbiome to Rheumatoid Arthritis

The gut microbiome may play a role in the development of rheumatoid arthritis (RA), according to a study appearing this week in Science Translational Medicine. While the specific triggers of RA are unknown, some hypothesize that mucosal immune responses are involved in the initiation or perpetuation of the systemic autoimmunity that occurs with the disease and, to investigate, a team led by University of Colorado Anschutz Medical Campus researchers analyzed immunoglobulin A and immunoglobulin G in blood samples from four people at risk of developing RA and two people in the early stages of the disease. They find that the antibodies reacted not only to RA-relevant autoantigens, but also to gut bacteria from the bacterial families Lachnospiraceae and Ruminococcaceae, and specifically Subdoligranulum bacteria. Further experimentation revealed a Subdoligranulum isolate from an RA patient that is targeted by monoclonal antibodies and activated T cells. When mice were colonized with this isolate, they developed RA symptoms such as inflamed joints. "Our data suggest one pathway by which the intestinal microbiome and mucosal immune responses can lead to systemic autoreactivity and joint pathology that is potentially a pathway in human RA," the study's authors write.