Oral Microbiome Linked to Onset of Rheumatoid Arthritis


Both patients with early rheumatoid arthritis (ERA) and those at-risk for developing rheumatoid arthritis (RA) had a significantly different oral microbiome when compared with a control group. Most notably, the pro-inflammatory discriminative zero-radius operational taxonomic units (zOTUs), Prevotella and Veillonella, were much more prevalent in these groups than in patients with no history of autoimmune conditions.

Patients with early rheumatoid arthritis (ERA) and those at-risk for developing the condition had similar oral microbiome, including pro-inflammatory species, when compared with a control group, according to a study published in Arthritis and Rheumatology.1

“Since the oral microbiome may play a role in RA onset and may thus be a target for RA prediction or even prevention, information on patients with ERA and individuals at risk of RA is most relevant,” stated investigators. “However, data on these specific groups is currently very limited. Our aim was therefore to assess the oral microbiome and the periodontal condition in patients with ERA and individuals at risk of RA, compared to each other and compared to healthy controls.”

RA is often linked to the antibodies rheumatoid factor (RF) and antibodies against citrullinated proteins (ACPA), which may appear years before clinical diagnosis. The study, based on data of a larger cohort-study, was the first to analyze microbial composition of several oral niches in at-risk patients.

Between November 2017 until July 2019, 150 patients were recruited and placed into 3 groups of 50: patients with ERA (2010 ACR/EULAR criteria), individuals at risk of RA, and a control group with no autoimmune conditions. Both the ERA group and at-risk group were recruited at Reade, a rheumatology clinic located in Amsterdam, The Netherlands. ERA was defined as having been diagnosed with RA in the previous year. In group 2, patients had increased levels of RF and/or ACPA coupled with inflammatory-type arthralgia. The Academic Centre for Dentistry Amsterdam recruited group 3 individuals who were matched for sex and age of the ERA and at-risk groups.

Individuals completed a medical questionnaire to rule out comorbidities and other confounders, including any antibiotics received in the past 3 months. The questionnaire included questions about general oral hygiene measures and how long it had been since they brushed their teeth. A dentist performed an oral exam and scored patients on bleeding on probing (BOP), pocket probing depth (PPD), and periodontal inflamed surface area (PISA). Subgingival dental plaque, saliva, and tongue coating was assessed using 165 rDNA amplicon sequencing and compared the different groups using permutational multivariate analyses of variance (PERMANOVA). Additionally, blood was drawn to determine levels of RF and ACPA. For the purpose of the study, RF levels >5.0 kU/l and/or ACPA levels >10.0 kU/l were considered seropositive. Patients were categorized according to periodontitis status using the Community Periodontal Index of Treatment Need (CPITN). Participants did not have any significant differences in factors that may influence oral microbiome, such as the use of antibiotics, smoking and drinking habits, and oral hygiene.

There was also no difference in BOP (p=0.70), PPD (p=0.30), or PISA (p=0.56) between the groups. Additionally, at-risk individuals were analyzed for confounding factors to compare ACPA positive and ACPA negative results, and no differences were found.

PERMANOVA analysis revealed that patients with ERA and those at risk of RA had significantly different microbial composition of stimulated saliva (F=2.08, p<0.001) and tongue coating (F=2.04, p=0.008), but not plaque (p=0.51), when compared with the control group. Discriminative zero-radius operational taxonomic units (zOTUs), Prevotella and Veillonella, were also at higher levels in the saliva and tongue coating compared of both ERA patients and at-risk individuals. As these are considered pro-inflammatory, this may suggest that microbiome dysbiosis contributes to RA and that there is a link between oral microbiome and the onset of RA.

“To complement the currently available cross-sectional data, future studies should also include a longitudinal aspect, preferably with large cohorts and consistent data collection to aid the application of advanced methods, using artificial intelligence, for oral-systemic link prediction,” concluded investigators. “The current study does show similarities in the oral microbiome between ERA patients and at-risk individuals, both presenting with increased relative abundance of potentially pro-inflammatory species compared to healthy controls, and thus points toward a possible role for the oral microbiome in RA onset.”


Kroese JM, Brandt BW, Buijs MJ, et al. The oral microbiome in early rheumatoid arthritis patients and individuals at risk differs from healthy controls [published online ahead of print, 2021 May 4]. Arthritis Rheumatol. 2021;10.1002/art.41780. doi:10.1002/art.41780

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