Gut bacteriome, mycobiome and virome alterations in rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a chronic destructive autoimmune disease of the joints which causes significant pain, functional disability, and mortality. Although aberrant immune cell activation induced by the imbalance between T helper Th1/Th17 and Treg cells is implicated in the RA development, its etiopathogenesis remains unclear. The presence of mucosal inflammation and systemic IgA-isotype-autoantibodies (anti-citrullinated peptide antibodies and rheumatoid factor) in pre-clinical RA supports the mucosal origin hypothesis involving altered microbiota in disease development. The gut microbiota comprises diverse bacteria, fungal and viral components, which are critical in developing host immunity. Alterations in microbial abundance are known to exacerbate or attenuate immune responses in the gut microenvironment subsequently affecting the joints. Further, these changes can provide biomarkers for disease activity and outcome in RA. Most of the research till date has been focused on describing gut bacterial components in RA. Studies on gut mycobiome and virome components in RA are relatively new and burgeoning field. Given the paucity of mycobiome or virome specific studies in RA, this review, discusses the recent findings on alterations in gut bacterial, fungal, and viral components as well as their role in regulating the spectrum of immune-pathogenic events occurring in RA which might be explored in future as a potential therapeutic target. Further, we provide an overview on inter-kingdom interactions between bacteria, fungi, and viruses in RA. The current understanding on gut microbiota modulation for managing RA is also summarised.

Mechanistic role of quercetin as inhibitor for adenosine deaminase enzyme in rheumatoid arthritis: systematic review

“…However, due to the changes in DC activity and distribution, RA and other autoimmune diseases can also result in autoimmune inflammation [ 28 ]. Changes in DCs are thought to be the primary cause of RA, increasing DC migration to the inflamed joint [ 29 ]. The upregulation of CCR6, a chemokine CCL20 receptor on DCs, is assumed to be the source of DC attraction to synovial tissue [ 30 ].…”

The regulation of self-tolerance and the role of inflammasome molecules

“…Not only is IL-18 linked to autoimmune diseases such as T1D and SLE, IL-18 has also been shown to play a key role in the maintenance of the intestinal epithelial barrier and regulation gut microbiota composition ( 63 , 64 ). Dysbiosis of gut microbiota has been suggested as a risk factor for the development of autoimmunity ( 65 , 66 ).…”

Causal associations between gut microbiota and synovitis–tenosynovitis: a two-sample Mendelian randomization study

“…Based on the research of Liang et al, fecal comparative analysis of RA patients and healthy people indicated that the contents of Flavobacterium , Eisenbergia , Escherichia coli , and Klebsiella in the feces of RA patients were higher, while the contents of Enterococcus , Pseudomonas , and Fusobacterium in the feces of healthy individuals were higher ( Liang et al, 2023 ). According to some studies, fecal samples from RA patients were analyzed and showed an increase in Wallemia and Candida species abundance, while Trichosporon , Scedosporium , and Pholiota species abundance decreased, which further indicated that the difference in the fungal microbiome might contribute to the inflammatory reaction in RA patients ( Dagar et al, 2022 ). According to other studies, Lactobacilli was related to the onset of OA, which also could be diagnosed and treated through Lactobacilli ( Marchese et al, 2023 ).…”