Molecular Mimicry Between Gut Microbiome and Rheumatoid Arthritis: Current Concepts

Rheumatoid arthritis (RA) represents an autoimmune condition impacted by a combination of genetic and environmental factors, with the gut microbiome (GMB) being one of the influential environmental factors. Patients with RA display notable modifications in the composition of their GMB, characterised by decreased diversity and distinct bacterial alterations. The GMB, comprising an extensive array of approximately 35,000 bacterial species residing within the gastrointestinal tract, has garnered considerable attention as a pivotal contributor to both human health and the pathogenesis of diseases. This article provides an in-depth exploration of the intricate involvement of the GMB in the context of RA. The oral-GMB axis highlights the complex role of bacteria in RA pathogenesis by producing antibodies to citrullinated proteins (ACPAs) through molecular mimicry. Dysbiosis affects Tregs, cytokine levels, and RA disease activity, suggesting that regulating cytokines could be a strategy for managing inflammation in RA. The GMB also has significant implications for drug responses and toxicity, giving rise to the field of pharmacomicrobiomics. The composition of the microbiota can impact the efficacy and toxicity of drugs, while the microbiota's metabolites can influence drug response. Recent research has identified specific bacteria, metabolites, and immune responses associated with RA, offering potential targets for personalised management. However, several challenges, including the variation in microbial composition, establishing causality, accounting for confounding factors, and translating findings into clinical practice, need to be addressed. Microbiome-targeted therapy is still in its early stages and requires further research and standardisation for effective implementation.