Oral Microbiome Dysbiosis and Citrullination in Rheumatoid Arthritis

Rheumatoid arthritis and periodontal diseases, both characterized by chronic inflammation, share many common risk factors, sparking interest in understanding their established association. Emerging research has shed light on the link between these two diseases potentially occurring through the intricate interactions within the oral microbiome. The enrichment of pathogenic strains and species in this microbial community disrupts the delicate balance of both ecological and immunological homeostasis with the host. Particular attention has been paid to the role of key pathogens, such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, known for their immunomodulatory abilities. The generation of an autoimmune response against proteins modified by citrullination is known to be a key step in the pathogenesis of RA. Importantly, the bidirectional citrullination mediated by both host innate immune cells and oral bacteria generates citrullinated peptide neoepitopes, which may serve as potential triggers for the loss of tolerance and subsequent autoimmunity in susceptible individuals. This review highlights the importance of understanding the mechanisms through which oral microbiome dysbiosis and citrullination contribute to the onset and progression of RA. Insights into these mechanisms not only advance pathobiological understanding but also offer potential therapeutic targets. Furthermore, we discuss the potential impact of nonsurgical periodontal treatment in modifying disease progression or mitigating RA, underscoring the critical role of periodontal health in managing systemic inflammatory conditions.