Contribution of the Human Microbiome and Proteus mirabilis to Onset and Progression of Rheumatoid Arthritis: Potential for Targeted Therapy

Abstract

The human microbiome has been shown to play a role in the regulation of human health, behavior, and disease. Data suggests that microorganisms that co-evolved within humans have an enhanced ability to prevent the development of a large spectrum of immune-related disorders but may also lead to the onset of conditions when homeostasis is disrupted. In many conditions, a link between dysbiosis (microbial imbalance or microbiome upset) has been identified and associated with immune conditions such as rheumatoid arthritis (RA). This review provides insight into how an individual’s unique microbiome, combined with a genetic predisposition and environmental factors may lead to the onset and progression of RA. While research efforts have been largely focused on Porphyromonas gingivalis in the generation of citrullinated products as a trigger in the onset and progression of RA, recent research efforts have also indicated that Proteus mirabilis may play a key role in the development of anti-citrullinated antibodies through shared epitope sequences IRRET and ESRRAL. Thus, this review also highlights how targeting dysbiosis with alternative approaches may help to reduce microbial resistance as well as potentially improve outcomes. Further investigation is needed to see if potential future treatments for RA could benefit from personalized medicine based on an individual’s unique microbiome