The Gut, Oral Health, and Rheumatoid Arthritis: Exploring the Link

Rheumatoid arthritis (RA) is a chronic condition where the immune system mistakenly attacks the joints, leading to inflammation, bone damage, and cartilage breakdown. Recent research has uncovered a strong connection between the bacteria in our gut and mouth with RA. This article delves into how imbalances in gut and oral bacteria may contribute to the development of RA. Another article will focus on non-medical treatments for RA, including evidence-based diets and specific nutrients that can help improve RA symptoms.

Gut Microbiota and RA

The bacteria living in our gut can have a big impact on the development of rheumatoid arthritis (RA). Inside our gut, there is a special type of immunity that involves certain cells called T cells. These T cells help regulate the immune system and maintain a healthy balance. When there is an imbalance of bacteria in the gut, some of these T cells can become overactive and make the immune system more sensitive to arthritis.

For example, having more beneficial bacteria like Bifidobacterium in the gut can produce a substance called butyric acid, a kind of short chain fatty acid, which helps reduce inflammation and increases the number of regulatory T cells. On the other hand, certain harmful bacteria and their byproducts can promote the production of another type of pro-inflammatory T cell called Th17, which contributes to the development of RA. [1]

The balance between two types of T cells, Th17 and regulatory T cells, is important for our immune system to work properly.

In an animal study, researchers transplanted fecal samples from RA patients into mice, and they found that the mice developed severe arthritis with an increased population of Th17 cells in their gut. [2]

But how does this relate to rheumatoid arthritis outside the gut? When the gut becomes “leaky” or permeable, allowing bacteria and their byproducts to enter the bloodstream, it can trigger an immune response and cause inflammation in the joints [1].

RA patients are found to have imbalances in their gut bacteria compared to healthy individuals in different studies [3,4]. 

While leaky gut is observed in RA patients, it may not be the primary cause of RA itself. It could result from the use of non-steroidal anti-inflammatory drugs (NSAIDs), commonly prescribed for RA treatment. NSAIDs can raise the risk of leaky gut in RA patients. Although leaky gut may not initiate RA, it enables bacteria and their byproducts to enter the bloodstream, potentially exacerbating the progression of RA [5,6].

Another substance called lipopolysaccharide (LPS), produced by certain bacteria in the gut, can also worsen arthritis. Studies have shown that higher levels of LPS in the blood are associated with more severe arthritis symptoms. In experiments with mice, injecting LPS into their gums led to both periodontitis (gum disease) and rheumatoid arthritis [7,8].

Periodontitis and RA

Besides the link between gut bacteria and RA, oral diseases also have a strong connection to RA. A study examined 132 RA patients and discovered that 72.7% of them also had periodontitis. The RA patients with periodontitis had higher disease activity scores (DAS28) and increased levels of inflammation markers like CRP, RF factors, and anti-CCP antibodies compared to those with RA alone [9]. This suggests that periodontitis can affect the severity of RA.

A study conducted in 2008 analyzing 4,461 subjects, including 103 RA patients, found that RA patients were 1.82 times more likely to have periodontitis compared to those with only RA [10],

Another study comparing 57 RA patients with 52 healthy controls, found that RA patients were 8 times more likely to have periodontitis than non-patients [11].

A Korean study in 2016 not only found that RA patients had more severe periodontitis but also observed a positive correlation between the severity of periodontitis and the duration of RA [12].

Mechanism of Gum Diseases Relating to RA

Various bacteria can cause periodontitis, with P. gingivalis being one of the most common. P. gingivalis is the only bacterium that secretes PAD enzyme, which leads to an immune system response and the production of anti-citrullinated protein (ACP) antibodies, potentially inducing autoimmune reactions.

Human organ and tissues are composed of proteins which are a combination of different amino acids. One of these amino acids is arginine, which undergoes a chemical change called “citrullination” under the action of PAD enzymes. Once arginine in the body’s own proteins is citrullinated, the immune system no longer recognizes them as self-tissues and produces antibodies against these substances, known as ACP antibodies.

Studies have found that 50% of newly diagnosed RA patients have ACP antibodies in their serum, and RA patients with ACP antibodies tend to have more severe symptoms and faster joint degradation [13].

A study conducted in Sweden in 2016, comparing 251 RA patients with 198 control subjects, found that ACP antibodies were present in RA patients five years before diagnosis, suggesting a higher prevalence of ACP antibodies in RA patients, which appeared years before the diagnosis of RA. This provides evidence supporting the relationship between P. gingivalis and the pathogenesis of RA [14].

Can We Treat RA by Targeting Periodontal Disease?

The link between gum disease bacteria and RA is summarized in a 2019 Johns Hopkins University study. Gum disease bacteria, like P. gingivalis, may have different effects at various stages of RA. Gum disease triggers ACP antibodies, which appear years before RA diagnosis. Gum disease and citrullination caused by these bacteria can lead to long-term inflammation, promoting RA onset. Early gum disease treatment may prevent RA, but treating gum disease after RA onset doesn’t seem to improve RA. The connection between gum disease, bacteria, and RA’s progression is still uncertain. [15]

Summary:

Gut microbiota influences RA development, and imbalances can lead to overactive immune responses and increased sensitivity to arthritis.

Beneficial bacteria reduce inflammation and promote regulatory T cell growth, while harmful bacteria stimulate pro-inflammatory T cells, contributing to RA.

Leaky gut allows bacteria and byproducts to enter the bloodstream, triggering joint inflammation.

RA patients exhibit imbalances in gut bacteria compared to healthy individuals.

Periodontal disease, especially periodontitis, is strongly associated with RA, with higher disease activity and inflammation markers in RA patients with periodontitis.