Tuesday 25 February 2014

Gum disease may be linked to arthritis

Gum disease may be linked to arthritis "Brushing your teeth well could help prevent arthritis," the Mail Online advises after scientists found that the bacteria that causes gum disease – P. gingivalis – may also damage joints. But the Mail's advice – though well meaning – is premature. This study involved mice and did not assess whether tooth brushing reduced the risk of arthritis.

That said, this was interesting research that provided a plausible and coherent mechanism whereby the common gum bacteria P. gingivalis caused the worsening of collagen-induced arthritis in mice.


This type of arthritis was essentially a "mouse version" of rheumatoid arthritis and was designed to mimic the human disease in many ways. The result may well have implications for humans affected by this common and distressing condition.

However, we need to be cautious in this assumption, as none of the experiments involved people. There may be more to be discovered in the human form of the disease, which has complex causes.

This research does appear to have broken new ground in suggesting a plausible mechanism that links gum disease to arthritis, something that has been suggested for years but has never been proven.

While we cannot say that brushing your teeth regularly will definitely prevent rheumatoid arthritis, we do know it can prevent tooth decay and gum disease. Read more about maintaining good oral health.

Where did the story come from?

The study was carried out by a large collaboration of researchers from different international universities and institutes and was funded by a similarly wide range of foundations, trusts, medical charities and research grants from across the globe.

It was published in the peer-reviewed science journal, PLOS Pathogens. This is an open accessjournal, so the study can be read free online.

The Mail Online's reporting of the story was generally accurate, but neglected to inform readers that the research was in a model of arthritis using mice, rather than humans.

No discussions of the research limitations were included in most media reports, leaving the impression that the findings were more solid than they were.

What kind of research was this?

This was a laboratory study involving mice. It aimed to see if, and how, bacteria involved in gum disease contributed to rheumatoid arthritis.

The researchers set the scene for their research by describing how clinical and epidemiological studies have suggested that chronic periodontal disease (PD, or gum disease) is one of the most prevalent infectious inflammatory diseases of mankind.

It has been linked to a number of systemic inflammatory diseases, such as cardiovascular diseases (CVD), rheumatoid arthritis (RA) and chronic obstructive pulmonary disease (COPD).

But what causes this link is not well understood. Two gum disease bacteria – Porphyromonas gingivalis and Prevotella intermedia – have been mooted as possible culprits, so this research sought to investigate their effects on rheumatoid arthritis in particular. The researchers used a mouse model of arthritis to study the causes of the disease as it shared many similarities with the human form.

What did the research involve?

Researchers created a version of rheumatoid arthritis in mice called collagen-induced arthritis, which broadly mimics the human form. They then infected the mice with two different bacteria known to cause gum disease and measured how these influenced the initiation, rate of progress and severity of arthritis. The biological causes of any disease changes were investigated further to gain a more complete understanding of what was happening.

The researchers took a host of biological measurements at the molecular and cellular levels to monitor the disease, as well as regularly examining the mice for swelling and joint nodule formation. They paid particular attention to citrullination, a chemical modification that can take place in some proteins.

The main analysis compared arthritis measures in mice that either were or were not deliberately infected with each of the two gum disease bacteria under investigation.

What were the basic results?

There were a number of individual laboratory results that led to the summary findings:
One gum disease bacterium, Porphyromonas gingivalis (but not the oral bacterium Prevotella intermedia), worsened collagen-induced arthritis by causing earlier onset, accelerated progression and enhanced severity of the disease, including significantly increased bone and cartilage destruction.
Looking into how this occurred, the researchers found that the ability of P. gingivalis to worsen collagen-induced arthritis was dependent on the expression of a unique enzyme called peptidylarginine deiminase (PAD), which converts arginine residues in proteins to citrulline, a compound thought to trigger inflammation in humans with rheumatoid arthritis.

How did the researchers interpret the results?

The authors concluded that their results "suggest bacterial PAD as the mechanistic link between P. gingivalis periodontal infection and rheumatoid arthritis".

Their thoughts on the implications of their findings were naturally cautious, stating that their findings "may create new perspectives in the treatment and prevention of RA [rheumatoid arthritis] in susceptible individuals."

Conclusion

The laboratory results showed a plausible and coherent mechanism by which the gum bacteria P. gingivalis can cause a deterioration of collagen-induced arthritis in mice. This sheds some light on how the same thing might happen in people.

However, we need to be quite cautious in this assumption, as none of the experiments involved people – there may be further complexities to be uncovered in the human form of the disease.

This research does appear to have broken new ground in suggesting a plausible mechanism that links gum disease to arthritis, an observed link that has evaded broad scientific explanation for a long time.

This may be just one of many mechanisms involved in this complex disease. The authors themselves are wise in saying that, "This ground-breaking conclusion will need to be verified with further research." This cautious conclusion recognises that the results, while promising, were preliminary findings in mice and are not on firm ground yet.

There was another important positive finding from the study, however. The researchers identified how a particular enzyme called peptidylarginine deiminase (PAD) was equally important in worsening the disease. This could potentially be a therapeutic target for future research efforts.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join theHealthy Evidence forum.

Links To The Headlines

Clean teeth can hold off arthritis: Scientists discover link between gum disease bacteria and early onset of the condition. Mail Online, February 24 2014

Links To Science

Maresz KJ, Hellvard A, Sroka A, et al. Porphyromonas gingivalis Facilitates the Development and Progression of Destructive Arthritis through Its Unique Bacterial Peptidylarginine Deiminase (PAD). PLOS Pathogens. Published online September 12 2013

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