A New Perspective on Rheumatoid Arthritis: Could Oral Bacteria be a Causative Factor?

A study was published in the Science Translational Medicine journal studying the role of oral bacteria in the pathogenesis of rheumatoid arthritis. The study was performed by analyzing patient samples from three universities namely, Stanford Unversity, Rockefeller University, and the University of Colorado.

Open Mouth

Open Mouth

Introduction

It is previously known that periodontal disease (inflammation of the gums and bone surrounding the teeth) is present more frequently in patients suffering from rheumatoid arthritis (RA). Also that RA patients with periodontal disease (PD) suffer severe forms of disease and their disease is more likely to be treatment resistant. Scientists reasoned that it suggests that periodontal disease (PD) may contribute to widespread inflammatory responses that are linked to ongoing joint inflammation in patients with RA.

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In PD, there is evidence of damage to the inner lining of the mouth that leads to the transfer of bacteria in the blood. These bacteria trigger immune responses in patients with RA activating an inflammatory response in the whole body. Scientists sought to determine the exact mechanism underlying this role of oral bacteria by studying two groups of rheumatoid arthritis patients, one with periodontal disease and the other without periodontal disease.

Presence of bacteria in the mouth

They first established the abundant presence of bacteria in the oral cavity in patients with RA by analyzing blood samples, obtained by finger stick method, using a technique called RNA sequencing analysis. Then, they determined if these bacteria were abundant from samples from other human body sites. Seeing that the number was significantly higher in the oral cavity, they concluded that entry and presence of bacteria in blood were higher in the oral cavity than in other bodily sites.

The associated immune response

Furthermore, they studied the relationship between the presence of these bacteria in the blood and the associated immune response in those patients. They observed that the percentage of monocytes, a type of immune cell, was positively associated with the presence of bacteria. The next step they took was to determine if these bacteria triggered a similar inflammatory response under lab conditions. And it was observed that these bacteria triggered a similar response under these conditions.

Specific mechanism

After this, they studied a gene expression (specific to inflammatory responses in RA patients with PD) to determine if there was evidence suggesting the link between oral bacteria in the blood circulation and the increase in the severity of rheumatoid arthritis. They found that RA patients’ severity of disease increases if they have periodontal disease. Learning this, they further studied whether RA patients have a specific form of antibodies called anti-citrullinated protein antibodies (ACPAs) that bind to modified forms of oral bacteria (citrullinated bacteria). After observing this finding, they looked if oral bacteria go through that specific process of modification that makes them vulnerable to the human immune response in patients with RA. They analyzed this by flow cytometry and observed that this specific type of modification was highest in oral bacteria.

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Findings

Conclusively, they found that patients with RA develop antibodies against this modified form of oral bacterial proteins. These findings suggested that damage to the inner lining of the oral cavity leads to the entrance of bacteria into the blood circulation and if repeated exposures occur, they can contribute to the mechanisms involved in the development of rheumatoid arthritis and possibly, worsening of RA in those patients.

Limitations

Scientists have highlighted the limitations of their approach and encouraged further research investigating similar associations in at-risk patients and in patients who have not taken any treatment for their rheumatoid arthritis. They also mentioned that further research might highlight if better oral care will help in better management f patients with RA.

Significance

This research highlights a potential mechanism in the development of rheumatoid arthritis and the relationship between periodontal disease-associated damage to the inner lining of the mouth and subsequent entrance of oral bacteria in the blood and their role in the development of RA and related worsening of the disease activity in the patients with RA. The studied mechanism can be helpful for steering further research studying this relationship and it can also lead to studying new forms of treatment targeting different steps of the observed mechanism. Although further research will provide information about the potential significance and possible treatments, the current study highlights new directions to possible prevention of periodontal disease-associated worsening of RA.

The funding and acknowledgment information can be found on the provided link.

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References

https://www.science.org/doi/10.1126/scitranslmed.abq8476

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