Targeting the gut for rheumatoid arthritis relief

UCL researchers have shown that damage to the intestinal lining plays an important role in the development of rheumatoid arthritis, paving the way for a new approach to treating the disease.

In the preclinical study, which used mouse models and patient samples, the research team suggests that restoring the intestinal barrier may offer a novel therapeutic approach to reduce the severity of rheumatoid arthritis (RA) symptoms. .

Rheumatoid arthritis is a chronic disease that causes joint pain, swelling, and inflammation. Despite understanding some of the genetic and environmental factors that could be involved in the development of arthritis, scientists still don’t fully understand what triggers the disease and how it speeds up. Recent research in this area is exploring how bacteria in the gut may be involved in the development of arthritis, with researchers suggesting that the growth of “bad” bacteria in the gut may play a role in triggering the disease. .

Co-lead author Prof Claudia Mauri (UCL Division of Infection & Immunity) said: “We wanted to know what was going on in the gut and if there were any changes in the gut lining, which generally acts as a barrier for protecting the body against bacteria “are a hallmark of disease and contribute to its development. “

Using preclinical mouse models and patient samples, the team found that blood markers of intestinal damage were increased compared to healthy people, even in the early stages of arthritis, and that these lesion markers increased as the disease progressed; and, unexpectedly, there were distinct signs of inflammation, as could be seen in inflammatory bowel disease. The team also showed that the intestinal lining became “permeable,” potentially allowing bacteria to pass through the intestinal lining into the body, thereby increasing inflammation both in the gut and potentially in the joints.

“Our results suggest that the intestinal lining is a therapeutic target. Importantly, we have found that the use of existing drugs that restore the integrity of the intestinal barrier, i.e. prevent the intestine from leaking or prevent inflammatory cells to travel to and from the intestine, could reduce the severity of arthritis in preclinical models, ”says Professor Mauri.

“Current treatments for rheumatoid arthritis do not appear to correct bowel problems and therefore may leave the patient vulnerable to disease reactivation due to continued inflammation in this area. In the future, we need to assess the therapeutic impact of treating the intestine. lining of rheumatoid arthritis patients in addition to their joints. Maintaining gut health through both diet and pharmacological intervention can be a valuable new strategy. “

The study is published in With, a Cell journal, and was funded by Versus Arthritis and UKRI / MRC.