Dysbiosis in the oral microbiomes of anti-CCP positive individuals at risk of developing rheumatoid arthritis.

Objectives: An increased prevalence of periodontitis and perturbation of the oral microbiome has been identified in patients with rheumatoid arthritis (RA). The periodontal pathogen Porphyromonas gingivalis may cause local citrullination of proteins, potentially triggering anti-citrullinated protein antibody production. However, it is not known if oral dysbiosis precedes the onset of clinical arthritis. This study comprehensively characterised the oral microbiome in anti-cyclic citrullinated peptide (anti-CCP) positive at-risk individuals without clinical synovitis (CCP+at risk).
Methods: Subgingival plaque was collected from periodontally healthy and diseased sites in 48 CCP+at risk, 26 early RA and 32 asymptomatic healthy control (HC) individuals. DNA libraries were sequenced on the Illumina HiSeq 3000 platform. Taxonomic profile and functional capability of the subgingival microbiome were compared between groups.
Results: At periodontally healthy sites, CCP+at risk individuals had significantly lower microbial richness compared with HC and early RA groups (p=0.004 and 0.021). Microbial community alterations were found at phylum, genus and species levels. A large proportion of the community differed significantly in membership (523 species; 35.6%) and structure (575 species; 39.1%) comparing CCP+at risk and HC groups. Certain core species, including P. gingivalis , had higher relative abundance in the CCP+at risk group. Seventeen clusters of orthologous gene functional units were significantly over-represented in the CCP+at risk group compared with HC (adjusted p value <0.05).
Conclusion: Anti-CCP positive at-risk individuals have dysbiotic subgingival microbiomes and increased abundance of P. gingivalis compared with controls. This supports the hypothesis that the oral microbiome and specifically P. gingivalis are important in RA initiation.
Competing Interests: Competing interests: ZC reports scholarship from the China Scholarship Council during the conduct of the study. Dr TD and JM reports grants from Colgate Palmolive, outside the submitted work. KM reports grants from the National Institute for Health Research (NIHR) Leeds Biomedical Research Unit and grants from Leeds Biomedical Research Centre during the conduct of the study. DD reports grants from NIHR, grants from Wellcome Trust, during the conduct of the study; grants from Colgate Palmolive, outside the submitted work. PE reports grants and personal fees from Pfizer, Merck Sharp & Dohme, AbbVie, Bristol-Myers Squibb, Roche, Samsung, Sandoz, and Eli Lilly and Company; and personal fees from Novartis and UCB outside the submitted work.
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