Gut Microbiota Directly Affects Inflammatory Arthritis

Despite extensive genetic studies of patients with rheumatoid arthritis (RA), researchers cannot successfully predict which individuals will ultimately develop disease. This knowledge gap has led many to assume that environmental triggers must be important for RA pathogenesis. Others have even proposed that the gut microbiota can provide such a trigger. This hypothesis is based on data indicating that gastrointestinal microbial imbalance can contribute to the development of autoimmune diseases. More specifically, not only do mice with clinical arthritis exhibit dysbiosis, but so, too, do patients with symptomatic RA.

Intestinal Dysbiosis Triggers Mucosal Immune Response
New research in mice suggests intestinal dysbiosis triggers a mucosal immune response that stimulates the T and B cells critical for the development of inflammatory arthritis. Widian K. Jubiar, MS, MD, postdoctoral fellow at the University of Colorado School of Medicine in Aurora, Colo., and colleagues used the murine collagen-induced arthritis (CIA) model to examine how both the microbiota and mucosal immune response change over time. They published their results March 13 in Arthritis & Rheumatology.¹

“From our study and the ongoing studies of many others in rheumatology and other fields, we know that there is an important role of the microbiome in educating our immune system,” writes co-author Kristine Kuhn, MD, PhD, assistant professor of medicine at the University of Colorado School of Medicine in an email interview with The Rheumatologist. “We believe that continued work in these areas will reveal unique pathways in how gut bacteria influence the development of many different autoimmune diseases.”

The Study
Dr. Jubiar and colleagues used the CIA model that induces arthritis in genetically susceptible DBA/1J mice via immunization with bovine collagen type II (CII) emulsified in complete Freund’s adjuvant (CFA). The mice are immunized on Day 0 and Day 21 and develop arthritis between Days 23 and 24. Researchers measured disease severity every two days by determining a mean clinical score from the animal’s four paws with 0=normal, 1=erythema, 2=swelling and 3=ankylosis. Not all of the mice treated in this way develop arthritis. Previous studies have shown the mice that developed disease had intestinal dysbiosis relative to those that were immunized and did not develop observable joint swelling.

In the current study, the investigators hypothesized the microbiota could modulate immune responses that lead to autoimmune arthritis. If true, then it should be possible to identify the critical point at which dysbiosis-modulated disease activity occurs. The team sought to identify this time point.