Interplay of Microbiota and Citrullination in the Immunopathogenesis of Rheumatoid Arthritis.

Microbiota is a balanced ecosystem that has important functions to the host health including development, defense, digestion, and absorption of dietary fibers and minerals, vitamin synthesizes, protection, and training the host immune system. On the other hand, its dysbiosis is linked to many human diseases such as rheumatoid arthritis (RA). The RA is an inflammatory autoimmune disorder caused by genetic and environmental factors; microbiota may be considered as a risk environmental factor for it. Citrullination is a post-translation modification (PMT) that converts the amino acid arginine to amino acid citrulline in certain proteins. These citrullinated proteins are recognized as a foreign antigen by the immune system resulting in the upregulation of inflammatory action such as in RA. The current work highlights the effect of both gut and oral microbiota dysbiosis on the development of RA, as well as discusses how the alteration in microbiota composition leads to the overgrowth of some bacterial species that entangled in RA pathogenicity. The evidence suggested that some oral and gut microbial species such as Porphyromonas gingivalis and Prevotella copri, respectively, contribute to RA pathogenesis. During dysbiosis, these bacteria can mediate the citrullination of either human or bacteria proteins to trigger an immune response that leads to the generation of autoantibodies.