Microbiome and mucosal inflammation as extra-articular triggers for rheumatoid arthritis and autoimmunity

Abstract

Purpose of review: Despite the progress toward understanding the molecular pathogenesis of rheumatoid arthritis (RA), its cause remains elusive. Genes are important but rather insufficient to explain the majority of RA cases. This review describes the novel data supporting the microbiome and its interactions with the human host as potential en('in')vironmental factors in RA pathogenesis.

Recent findings: Animal models of inflammatory arthritis have shown that the presence of bacteria in mucosal surfaces is sufficient to alter local and systemic host immune responses and elicit joint inflammation. Human RA studies have focused on three mucosal sites: the gut, the gingiva, and the respiratory tree. The oral microbiome, and specifically Porphyromonas gingivalis, has long been implicated. Novel sequencing technologies have allowed investigations into the role of the gut microbiome in the development of autoimmune arthritis. Most recently, the pulmonary parenchyma has also been described as yet another possible mucosal site of initiation of autoimmunity in RA.

Summary: Emerging data implicate the microbiome in RA pathogenesis. Mucosal sites exposed to a high load of bacterial antigens--such as the periodontium, lung, and gut--may represent the initial site of autoimmune generation. If validated, these findings could lead to the discovery of potential biomarkers and therapeutic approaches in the preclinical and clinical phases of RA.

Figure

Potential sites of microbiome involvement and related risk factors in the pathogenesis of RA. A. Periodontal disease is linked to increased RA prevalence and disease severity. The oral microbiome, specifically P. gingivalis through PAD activity, has been implicated. B. The lung mucosa has increased PAD activity and airway inflammation is more prevalent in both seropositive, at-risk subjects (i.e. anti-CCP positive) and RA patients. C. An altered gut microbiome has been identified in multiple animal models and in human RA.