Newly discovered gut microbe may be a trigger for rheumatoid arthritis: ScienceAlert

Rheumatoid arthritis affects 1 in 100 people worldwide. It causes inflamed, painful, and swollen joints, often in the hands and wrists, and can lead to loss of joint function as well as chronic pain and joint deformity and damage. The causes of this condition are unknown.

In our recently published study, my colleagues and I found an important clue to a potential culprit behind this disease: bacteria in your gut.

What causes rheumatoid arthritis?

Rheumatoid arthritis is an autoimmune disease, which means it develops when the body’s immune system begins to attack itself. Proteins called antibodies, which usually help fight off viruses and bacteria, start attacking the joints instead.

The origins of the antibodies that cause rheumatoid arthritis have been a field of study for many years. Some research has shown that these antibodies can start forming at sites like the mouth, lungs, and intestines more than 10 years before symptoms appear. But until now, it was unclear why the researchers were finding these antibodies in these particular areas.

We wanted to study what could trigger the formation of these antibodies. Specifically, we wondered if bacteria in the microbiome, a community of microorganisms that live in the gut, might be the ones that activate the immune response that leads to rheumatoid arthritis.

Since the microbes typically live at the same sites as the antibodies that cause rheumatoid arthritis, we hypothesized that these bacteria could trigger the production of these antibodies. We felt that although these antibodies were intended to attack bacteria, rheumatoid arthritis develops when they spread beyond the intestines to attack the joints.

First, we sought to identify the intestinal bacteria targeted by these antibodies. To do this, we exposed the bacteria present in the feces of a subset of people at risk of developing rheumatoid arthritis to these antibodies, which allowed us to isolate only the bacterial species that reacted and are related to antibodies.

We have discovered that a previously unknown species of bacteria is present in the intestines of about 20% of people who have been diagnosed with rheumatoid arthritis or who produce the antibodies that cause the disease.

As a member of the Cherokee Nation of Oklahoma, I suggested naming this species Subdoligranulum didolesgii (“didolesgii” means arthritis or rheumatism in Cherokee) as a nod to the contributions other Indigenous researchers have made to science as well as the fact that rheumatoid arthritis affects Indigenous people at a higher rate than others populations.

Subdoligranulum didolesgii has not been detected in the feces of healthy people before, and the prevalence of this bacterium in the general population is currently unknown.

We also discovered that these bacteria can activate specialized immune cells called T cells in people with rheumatoid arthritis. T cells drive inflammatory responses in the body and have been linked to the development of different autoimmune diseases.

These results suggest that these gut bacteria may activate the immune system of people with rheumatoid arthritis. But instead of attacking the bacteria, their immune system attacks the joints.

frameborder=”0″ allow=”accelerometer; automatic reading; clipboard-write; encrypted media; gyroscope; picture in picture” allow full screen >

Why this bacteria?

It is still unclear why people with rheumatoid arthritis develop an immune response to Subdoligranulum didolesgii. But we think it may be the culprit when it comes to rheumatoid arthritis, because this bacteria is only found in the intestines of people with rheumatoid arthritis, not in the intestines of healthy people.

Although many immune responses occur in the intestines, they are generally self-contained and do not spread to other parts of the body. However, we believe that a particularly strong intestinal immune response against Subdoligranulum didolesgii could allow antibodies to bypass the intestinal “firewall” and spread to the joints.

To confirm our hypothesis, we administered to mice an oral dose of Subdoligranulum didolesgii and followed their reaction. Within 14 days, the mice began to develop joint swelling and antibodies that attacked their joints.

The future of rheumatoid arthritis treatment

My colleagues and I hope this research can shed light on the origins of rheumatoid arthritis. Our next goal is to find out how common these bacteria are in the general population and to test whether the presence of these bacteria in the gut can lead to the development of rheumatoid arthritis in humans.

Importantly, antibiotics are unlikely to be a useful treatment for the microbiomes of patients with rheumatoid arthritis. Although Subdoligranulum didolesgii may trigger an autoimmune response in some people with rheumatoid arthritis, antibiotics kill both helpful and harmful bacteria in the gut. Also, eliminating the bacteria will not necessarily prevent the immune system from attacking the joints once it has started.

Nonetheless, we believe these bacteria can be used as tools to develop treatments for rheumatoid arthritis and hopefully ways to prevent the disease.The conversation

Meagan Chriswell, MD/PhD Candidate in Immunology, University of Colorado Anschutz Medical Campus

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Leave a Comment