Gut Bacteria May Trigger Rheumatoid Arthritis

Researchers in Colorado have discovered a gut bacteria that could trigger rheumatoid arthritis (RA) in individuals already at risk for the common autoimmune disease. The findings suggest it could be possible to target the strain of Subdoligranulum as a means of prevention in those susceptible.

“Work led by co-authors Drs. Kevin Deane, Kristen Demoruelle, and Mike Holers here at [University of Colorado School of Medicine] helped establish that we can identify people who are at risk for RA based on serologic markers, and that these markers can be present in the blood for many years before diagnosis,” says Kristine Kuhn, MD, PhD, associate professor of rheumatology at University of Colorado (UC). “When they looked at those antibodies, one is the normal class of antibody we normally see in circulation, but the other is an antibody that we usually associate with our mucosa, whether it be the oral mucosa, the gut mucosa, or the lung mucosa. We started to wonder, ‘Could there be something at a mucosal barrier site that could be driving RA?’”

The CU researchers, with the help of a group led by Bill Robinson, MD, PhD, at Stanford University, took the antibodies created by immune cells from individuals whose blood markers showed they were at risk for the disease and mixed them with the feces of the at-risk individuals to find the bacteria that were tagged by the antibodies.  

To further test their hypothesis, the researchers used animal models to host the newly discovered bacteria, a Subdoligranulum strain. Those experiments showed that not only did the bacteria cause the mice to develop the blood markers found in individuals at risk for RA, but some of the models showed development of full-blown RA as well.

“Our collaborators… [at] Benaroya Research Institute confirmed that the T cells in the blood of people with RA will respond to these bacteria, but people who are otherwise healthy do not respond to these bacteria,” Kuhn says. “Through studies in humans and animal models, we were able to identify these bacteria as being associated with the risk for developing RA. They trigger an RA-like disease in the animal models, and in humans, we can show that this bacterium seems to be triggering immune responses specific to RA.”

If the unique species of bacteria is indeed driving the immune response that leads to RA in individuals already at risk for the disease, Kuhn says, it might be possible to target the bacteria with medication to prevent that response from happening.  

“The next thing we want to do is identify, in larger populations of individuals at risk for RA, if these bacteria correlate with other genetic, environmental, and mucosal immune responses, and then ultimately, the development of RA,” Kuhn says. “Then we could say, ‘This is a marker that's useful in helping predict who will go on to develop RA,’ and apply prevention strategies. The other opportunity there is that if we can understand how it is triggering these immune responses, we might be able to block the bacteria’s ability to do that.”

Kuhn adds that rather than a “sledgehammer” effect of traditional antibiotics for RA that wipe out a large group of bacteria, it may be possible to selectively target Subdoligranulum.  “There are a lot of different technologies that are just starting to come out that could selectively target a bacterium in the gut microbiome, for example, to prevent it from having immunogenic effects on the host,” Kuhn adds.

The findings  were published in the journal Science Translational Medicine.