A new study from the Netherlands found that people at risk of developing rheumatoid arthritis (RA) and people with early RA (ERA) had higher levels of two groups of bacteria, Prevotella and Veillonella, in their saliva.
Both groups also had higher levels of Veillonella in the bacterial coating of their tongue.
Prevotella and Veillonella are potentially pro-inflammatory bacteria, and their relative abundance suggests a possible link between oral microbes and RA.
This study builds on previous research that found that people with ERA, at risk of developing RA, and with diagnosed RA tend to experience higher rates of periodontal disease and changes in their oral and intestinal microbiota.
If confirmed, these findings could help illuminate how RA develops and improve preclinical testing for RA and ERA.
An estimated 1.5 million people living in the United States alone have RA, an autoimmune disease that causes joint pain, swelling, and eventually damage.
Researchers continue to look for new ways to diagnose RA, especially in its early stages. That is because the earlier a person receives a proper diagnosis of and treatment for RA, the better their chances of good outcomes, such as limiting joint damage and functional loss.
Researchers also remain uncertain as to what exactly causes RA to develop, although it seems to depend on a mix of genetic and environmental factors.
In more recent years, RA researchers have been exploring the link between ERA, people at risk of RA, and the changes in their oral and intestinal microbiota, or community of microbes.
It seems people with ERA and at risk of RA have abnormal levels of certain bacteria in the mucus that lines the mouth and intestines. They also seem to be more likely than other people to have periodontal disease, or gum disease.
That is why a team of researchers from the Academic Centre for Dentistry of Amsterdam (ACTA) set out to analyze the microbial populations and periodontal condition of people with ERA, those at risk of RA, and a control group of people without these conditions for comparison.
Several studies seem to show that oral microbes — in particular anaerobic bacteria, which do not require oxygen — may play a role in the development of RA.
A 2009 study highlights three types of anaerobic bacteria occurring in the oral cavity that have been identified in joint fluid from people with RA. Several studies show that antibodies for certain types of anaerobic bacteria associated with periodontal disease may play a role in the development of RA.
Some researchers think these bacteria may cause an RA-associated immune response by producing proteins that trigger the formation of anti-citrullinated protein antibodies (ACPAs).
These compounds appear to promote inflammatory responses in different types of cells, including bone cells. Some studies have shown that this response ACPAs promote may be involved in the mediation of bone damage in the joints of people with RA.
For these and other reasons, the detection of ACPAs is now considered the most specific biomarker for RA in serum, which is the fluid component of blood.
The detection of ACPAs in serum also seems to help predict RA development several years before a person has clinical RA or experiences symptoms and receives an RA diagnosis.
That is why several research teams, including the team involved in the current study, have been exploring how changes in the composition and other components of the oral microbiome may relate to the onset of RA.
In the new study, researchers analyzed the oral microbiome and periodontal status of three groups of 50 people.
People in the first group had ERA, and the second group included people at risk of RA (people with serum ACPAs or arthralgia). People in the third group did not have RA and were not at risk, did not have autoimmune conditions, and were generally healthy.
Each participant was examined by a dentist to assess their periodontal condition. Dentists checked whether their gums bled with probing, the inflamed gum surface area, and how deep into the gum line dental tools could probe.
They also examined how many teeth each participant had, how many of their teeth were missing, decayed, or filled, and whether a person wore a removable denture. They also asked each participant about the last time they brushed their teeth and what their regular oral hygiene measures were.
In addition, the scientists collected from each participant samples of the tongue coating or film, saliva, and subgingival dental plaque, which is found below the gum.
After using devices to amplify the DNA present in the samples, they collected, analyzed, and quantified the microbial populations within the samples. They then compared microbial differences between the three groups.
The team identified no difference in periodontal conditions between the groups. There was also no difference in dental plaque samples.
Yet differences did exist between the oral saliva and tongue coating of people with ERA and at risk of RA compared with the control group.
Levels of bacteria belonging to the genera Prevotella and Veillonella were higher in saliva samples from people with ERA and at risk of RA compared with the control group. Veillonella bacterial levels were also higher in the tongue coatings of the RA groups than in those of people in the control group.
According to the authors, these findings suggest that a possible link between the oral microbe and RA may truly exist.
This also suggests that bacteria from these two genera, as well as some others already reported to be involved in RA onset, could help trigger immune responses that influence the development of RA.
The authors explain that these findings correspond to those of previous studies showing that people with new-onset RA and established RA had increased levels of oral Prevotella bacteria. The results also support research that found increased levels of Prevotella bacteria in the gut microbiome of people at risk of RA or with ERA.
The authors write that some strains of Prevotella can cause chronic inflammation, which can trigger immune cells to be released throughout the body. They add that in some cases, microbial dysbiosis, or microbial imbalances, partially resolves with RA treatment.
“This is an interesting study that, in my mind, achieves two goals. First, it provides further support for the mucosal origin hypothesis for RA. And second, it suggests that dysbiosis occurs even before disease onset and thus may play a role in RA disease pathogenesis.”
Dr. Kronzer believes this research is “an important step in a long path to understanding the etiology of this important disease.”
MNT also contacted Johanna Kroese from ACTA, the corresponding author of the study. She explained:
“Our results indicate a possible role for oral bacteria in triggering the onset of RA. Targeting these bacteria might lower the risk of developing RA. Future research can focus on strategies to target these bacteria and improving oral health, and might eventually lead to the development of measures for RA disease prevention.”
While the study had many strengths, it also had some notable flaws.
People within the ERA group were receiving treatment for RA, while people at risk of RA and those in the control group were not. The researchers also did not collect information on some factors that may influence dental plaque, such as diet.
To confirm their findings, the authors say future studies must collect multiple datasets over longer periods of time, ideally using large groups of people and consistent collection methods.
Nevertheless, these findings may have uncovered yet another stepping stone in the complex, elusive development process of RA. This could be good news for the millions of people living with RA, and the healthcare professionals trying to diagnose and treat them.
As Johanna Kroese explained to MNT,although further research is needed, “improving oral health is relevant for the entire population, and it wouldn’t hurt to already pay attention to oral health in persons at risk of developing RA.”