Differences in the Oral Microbiome in Patients With Early Rheumatoid Arthritis and Individuals at Risk of Rheumatoid Arthritis Compared to Healthy Individuals

Abstract

Objective It has been suggested that rheumatoid arthritis (RA) may originate at the oral mucosa. The aim of the present study was to assess the oral microbiome and periodontal condition in patients with early RA and individuals at risk of developing RA compared to healthy controls. Methods Three groups were recruited (n = 50 participants per group): 1) patients with early RA (meeting the American College of Rheumatology/European Alliance of Associations for Rheumatology 2010 classification criteria), 2) individuals at risk of developing RA (those with arthralgia who were positive for RA‐associated autoantibodies), and 3) healthy controls. A periodontal examination was conducted to assess the presence of bleeding on probing (BOP), pocket probing depth (PPD), and periodontal inflamed surface area (PISA). The microbial composition of subgingival dental plaque, saliva, and tongue coating was assessed using 16S ribosomal DNA amplicon sequencing, and findings were compared between groups with permutational multivariate analysis of variance (PERMANOVA). Results There were no significant differences in any of the 3 periodontal variables between patients with early RA, at‐risk individuals, and healthy controls (P = 0.70 for BOP, P = 0.30 for PPD, and P = 0.57 for PISA, by Kruskal‐Wallis test). PERMANOVA analyses comparing microbial composition between the groups showed significant differences in the microbial composition of saliva (F = 2.08, P = 0.0002) and tongue coating (F = 2.04, P = 0.008), but not subgingival dental plaque (F = 0.948, P = 0.51). However, in post hoc tests, no significant differences in microbial composition of the saliva or tongue coating were observed between the early RA group and the at‐risk group (F = 1.12, P = 0.28 for saliva; F = 0.834, P = 0.59 for tongue coating). In assessing microbial diversity based on the number of zero‐radius operational taxonomic units per sample, Prevotella in the saliva and Veillonella in the saliva and tongue coating were each found at a higher relative abundance in samples from patients with early RA and at‐risk individuals compared to healthy controls. Conclusion The results show similarities in the oral microbiome between patients with early RA and at‐risk individuals, since in both groups, the oral microbiome was characterized by an increased relative abundance of potentially proinflammatory species when compared to that in healthy controls. These findings suggest a possible association between the oral microbiome and the onset of RA.

Salivary Microbiota and Host-Inflammatory Responses in Periodontitis Affected Individuals With and Without Rheumatoid Arthritis

“…In our study, P. gingivalis was not included among the top 30 most important ASVs for the classification of samples and those with variable importance in projection (VIP) > 1. In agreement with our results, Kroese and colleagues reported that P. gingivalis was not identified as a discriminative zero-radius operational taxonomic units, zOTUs ( Kroese et al., 2021 ). Furthermore, previous 16S rRNA gene sequencing studies, investigating the subgingival microbiome of patients with RA compared to osteoarthritis and healthy controls without periodontitis did not show subgingival compositions discriminating between RA and osteoarthritis ( Mikuls et al., 2018 ), nor between RA and healthy controls regarding the periodontal pathogens P. gingivalis or A. actinomycetemcomitans ( Lopez-Oliva et al., 2018 ).…”

Association of Bitter Taste Receptor T2R38 Polymorphisms, Oral Microbiota, and Rheumatoid Arthritis

“…Since genetic variations in TAS2R38 have functional consequences that, in addition to taste perception, may contribute to antimicrobial responses [18,20], we investigated the buccal microbiome in our RA and non-RA control subjects, many of whom were at risk for developing future RA, and compared the microbiome across TAS2R38 genotypes. Our findings are consistent with other reports finding the enrichment of periodontal pathogens in oral, pulmonary, and gastrointestinal microbiomes obtained from individuals at risk for RA [35][36][37][38][39][40]. Relative depletion of P. gingivalis has been reported in RA patients compared to anti-citrullinated protein autoantibody (ACPA)-positive individuals who are at risk for developing future RA [38].…”

Influence of Oral Microbiota on the Presence of IgA Anti-Citrullinated Protein Antibodies in Gingival Crevicular Fluid

“…Cheng et al compared early RA and at risk patients with RA to healthy controls and showed dysbiosis, including an increase of Porphyromonas gingivalis , in the periodontally healthy microbiota (and altered diseased subgingival microbiota) of at risk RA compared with HC [ 35 ]. Kroese et al reported similarities in oral microbiota of early patients with RA and patients with RA at risk, since in both groups, the oral microbiota were characterized by an increased relative abundance of potentially proinflammatory species when compared to that in healthy controls [ 15 ]. Prevotella salivae, Veillonella , and Prevotella were more abundant in the early RA group and RA at risk group compared to the healthy control group.…”

“…Prevotella salivae, Veillonella , and Prevotella were more abundant in the early RA group and RA at risk group compared to the healthy control group. The genus P gingivalis was not identified in this study as a discriminative microorganism [ 15 ]. The differences in outcomes between the various studies can be explained by differences between study groups, such as including patients at different stages of RA, differences in disease activity, differences in therapy, and including patients at risk or early and established RA.…”

“…They stated that a growing body of evidence supports that oral bacteria, such as Porphyromonas gingivalis , contribute to the pathogenesis of RA, although the genetic background of patients may also play a role [ 13 ]. Studies relying on the high-throughput sequencing 16S ribosomal DNA gene ampliconspointed to Prevotella as a periodontal taxa of interest among the oral microbiota of patients with RA [ 14 , 15 ].…”