Researchers discover hidden link between gut bacteria and arthritis

Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are progressive inflammatory conditions that cause joint damage over time.

Genetic factors play a role in both diseases, but they do not fully explain who develops arthritis. Environmental factors, including smoking, increase the risk, particularly in genetically susceptible individuals. Now, new research suggests that gut bacteria and their byproducts may be a crucial trigger for inflammatory arthritis.

Scientists have found that people with RA and SpA often show signs of microbial imbalances in the gut, a condition known as dysbiosis. In RA, the "mucosal origins hypothesis" suggests that immune system dysfunction starts at mucosal sites such as the intestines before spreading to the joints.

Studies have identified a preclinical phase lasting 5–10 years, during which intestinal dysbiosis, increased inflammatory markers, and specific autoantibodies appear. Recent findings also highlight a particular strain of gut bacteria, Subdoligranulum, as a potential RA trigger.

Similarly, about half of SpA patients exhibit intestinal inflammation at the microscopic level. This has led researchers to explore the "gut-joint axis"—the idea that immune disturbances begin in the gut and later impact the joints. However, the precise mechanisms linking gut bacteria to arthritis remain unclear.

A groundbreaking study from the University of Colorado sheds light on how gut bacteria contribute to arthritis. Led by Kristine Kuhn, MD, PhD, researchers identified a connection between tryptophan metabolism and inflammation. Tryptophan is an essential amino acid obtained from food, aiding in protein synthesis, muscle growth, and neurotransmitter production.

The study, published in the Journal of Clinical Investigation, found that when gut bacteria break down tryptophan, they produce inflammatory byproducts such as indole. In experiments with mice, those given antibiotics to remove their gut bacteria did not develop arthritis or produce indole.

Similarly, when mice were fed a diet low in tryptophan, they also remained free of arthritis. These findings suggest that microbial breakdown of tryptophan into indole plays a critical role in triggering the disease.

Further analysis revealed that indole increases inflammatory T-cells while reducing regulatory T-cells, which normally help maintain immune balance. Indole also enhances the production of inflammatory antibodies, worsening immune system attacks on the joints.

Understanding the role of tryptophan metabolism in arthritis opens new possibilities for treatment. Kuhn and her colleagues propose that blocking indole production or shifting tryptophan metabolism toward anti-inflammatory pathways could provide relief.

Since diet affects gut bacteria, dietary interventions might help reduce inflammation. Research suggests that fiber-rich, plant-based diets, such as the Mediterranean diet, promote a gut microbiome that favors anti-inflammatory tryptophan metabolism.

Beyond dietary changes, the Division of Rheumatology at the University of Colorado is working on ways to identify people at high risk for RA. By detecting specific blood markers, researchers hope to develop early interventions that could prevent or slow the disease.

Although much work remains, this research could lead to new therapeutic approaches that mitigate arthritis before irreversible joint damage occurs.

The connection between gut bacteria and inflammatory arthritis highlights the complex interplay between the microbiome and the immune system.

By targeting this pathway, scientists may be able to develop treatments that not only manage symptoms but also prevent disease onset altogether.

According to the Mayo Clinic, signs and symptoms of rheumatoid arthritis may include:

Early rheumatoid arthritis tends to affect your smaller joints first — particularly the joints that attach your fingers to your hands and your toes to your feet.

As the disease progresses, symptoms often spread to the wrists, knees, ankles, elbows, hips and shoulders. In most cases, symptoms occur in the same joints on both sides of your body.

About 40% of people who have rheumatoid arthritis also experience signs and symptoms that don't involve the joints. Areas that may be affected include:

Rheumatoid arthritis signs and symptoms may vary in severity and may even come and go. Periods of increased disease activity, called flares, alternate with periods of relative remission — when the swelling and pain fade or disappear. Over time, rheumatoid arthritis can cause joints to deform and shift out of place.

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