Study Reveals How Oral Bacteria Can Worsen Rheumatoid Arthritis

Understanding the Link Between Periodontal Disease and Rheumatoid Arthritis

JAPAN: A new study published by researchers at Tokyo Medical and Dental University (TMDU) has shed light on the connection between oral bacteria and rheumatoid arthritis (RA), an autoimmune disease that primarily affects the joints. The research, published in the International Journal of Oral Science on 15 August 2024, explores how the periodontal pathogen Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) contributes to the worsening of RA symptoms.

Periodontal disease, a common dental disorder, is caused by the accumulation of bacterial biofilm around the teeth and can lead to tooth loss if untreated. However, the study reveals that the impact of these bacteria extends beyond oral health. “Our research findings provide new insights into the link between periodontal pathogenic bacteria and the exacerbation of arthritis through inflammasome activation,” said Professor Toshihiko Suzuki, one of the study’s lead authors.

Research Methodology: Exploring the Role of Bacteria in Arthritis

The research team focused on understanding how A. actinomycetemcomitans might worsen RA. Using the collagen antibody-induced arthritis mouse model—an established model that mimics aspects of RA in humans—the scientists examined the effect of bacterial infection on arthritis progression. They observed increased swelling in the limbs, cellular infiltration in the joints, and elevated levels of the inflammatory cytokine interleukin-1b (IL-1b) in infected mice. These findings confirm the role of oral bacteria in worsening arthritis.

The study also found that macrophages, a type of immune cell, were implicated in the process. Injecting clodronate, a chemical that depletes macrophages, alleviated the symptoms of RA in the mice, further demonstrating the immune cells’ role in driving inflammation.

Inflammasome Activation and the Role of Caspase-11

In their detailed investigations, the researchers discovered that A. actinomycetemcomitans infection triggered the activation of a multiprotein complex known as the inflammasome, which plays a crucial role in regulating the body’s inflammatory response. By analyzing macrophages derived from mouse bone marrow, they found that infection with the bacteria heightened IL-1b production, leading to this inflammasome activation.

Notably, caspase-11, a key protein involved in inflammasome regulation, was identified as a critical factor in the disease mechanism. In caspase-11-deficient mice, inflammasome activation due to A. actinomycetemcomitans was suppressed, and these animals showed less severe arthritis symptoms. This crucial discovery suggests that targeting caspase-11 could help mitigate inflammation caused by bacterial infection in RA patients.

Future Implications for Treating Rheumatoid Arthritis

The findings from this study have significant implications for the future treatment of RA. Dr. Tokuju Okano, the study’s lead author, noted that the research could pave the way for new therapeutic strategies. “Our suggestion to inhibit inflammasome activation could attenuate the expansion of inflammation to joints, resulting in a recovery from arthritis symptoms,” he explained.

Looking ahead, the research team is optimistic that their discoveries could lead to broader applications in treating other systemic diseases linked to periodontal bacteria, including Alzheimer’s disease. “The outcome of our work could contribute to the development of treatment strategies for not only arthritis but also other systemic diseases,” Dr. Okano added.

This study reinforces the growing body of evidence that oral health has far-reaching effects on overall health, particularly in autoimmune and inflammatory conditions such as rheumatoid arthritis.