Can gut bacteria cause rheumatoid arthritis?

Researchers at the University of Colorado School of Medicine have found that a unique bacterium found in the gut can trigger rheumatoid arthritis (RA) in people who are already at risk for the autoimmune disease.

Christine Kuhn, MD, assistant professor of rheumatology, led a team of researchers from the Division of Rheumatology in the study, which was published Oct. 26 in the journal Science Translational Medicine. CU Medical School student Meaghan Criswell is the paper’s lead author.

“Work led by co-authors Drs. Kevin Dean, Kristen Demaruel and Mike Hollers here at CU has helped establish that we can identify people at risk for RA based on serological markers and that these markers can be present in the blood for many years before diagnosis,” Kuhn says. “When they looked at these antibodies, one is a normal class of antibodies that we normally see in circulation, and the other is an antibody that we normally associate with mucosa, whether it’s mucous lining of the mouth, intestines or lungs mucous membrane. We began to wonder, “Could there be something at the mucosal barrier site that could be causing RA?”

Discovery of a new bacterium

CU researchers, with the help of a team led by Bill Robinson, MD, of Stanford University, took antibodies created by immune cells from people whose blood markers showed they were at risk for the disease, and mixed them with the feces of people at risk to find bacteria which were labeled with antibodies.

To further test their hypothesis, the researchers used animal models to house the newly discovered bacteria. These experiments showed that the bacteria not only caused animal models to produce blood markers found in people at risk for RA; but some of the models also showed the development of full-scale RA.

“Our collaborators, led by Drs Eddie James and Jane Buckner of the Benaroya Research Institute, confirmed that T cells in the blood of people with RA will respond to these bacteria, but people who are otherwise healthy do not,” says Kun. . “Through studies in humans and animal models, we have been able to identify these bacteria as being associated with the risk of developing RA. They cause an RA-like disease in animal models, and in humans we can show that this bacteria appears to trigger immune responses, characteristic of RA”.

A new goal for RA

When a unique species of bacteria really moves immune response that leads to RA in people who are already at risk for the disease, Kuhn says, it may be possible to target the bacteria with drugs to prevent such a reaction.

“What we want to do next is to determine in large populations of people at risk for RA whether these bacteria correlate with other genetic, environmental, and immune mucosal responses and ultimately with the development of RA,” Kuhn says. . “Then we could say, ‘This is a marker that helps predict who will develop RA in the future,’ and apply prevention strategies. Another possibility is that if we can understand how it causes these immune responses, we may have the ability to block the bacteria’s ability to do this.”

Study of the trigger mechanism

The study took five years to conduct and analyze, and Kuhn says he was helped by people who identified themselves as at risk for RA and volunteered to support the research effort. Ultimately, the researchers want to study exactly how the bacteria trigger the immune response, as well as different methods of preventing the response.

“There are many different technologies that are just beginning to emerge that can selectively target a bacterium in the gut microbiome, for example, to prevent it from having an immunogenic effect on the host,” she says. “For a long time, people believed that antibiotics could be a useful therapy for RA, but instead of a traditional antibiotic killing a large group of bacteria, we could selectively target that bacteria or its effects.”