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Review
. 2023 Jan 27:13:1092118.
doi: 10.3389/fcimb.2023.1092118. eCollection 2023.

Gut-joint axis: Gut dysbiosis can contribute to the onset of rheumatoid arthritis via multiple pathways

María Del Socorro Romero-Figueroa  1 , Ninfa Ramírez-Durán  2 , Alvaro José Montiel-Jarquín  3 , Gabriel Horta-Baas  4
Affiliations
Review

Gut-joint axis: Gut dysbiosis can contribute to the onset of rheumatoid arthritis via multiple pathways

María Del Socorro Romero-Figueroa et al. Front Cell Infect Microbiol. .

Abstract

Rheumatoid Arthritis (RA) is an autoimmune disease characterized by loss of immune tolerance and chronic inflammation. It is pathogenesis complex and includes interaction between genetic and environmental factors. Current evidence supports the hypothesis that gut dysbiosis may play the role of environmental triggers of arthritis in animals and humans. Progress in the understanding of the gut microbiome and RA. has been remarkable in the last decade. In vitro and in vivo experiments revealed that gut dysbiosis could shape the immune system and cause persistent immune inflammatory responses. Furthermore, gut dysbiosis could induce alterations in intestinal permeability, which have been found to predate arthritis onset. In contrast, metabolites derived from the intestinal microbiota have an immunomodulatory and anti-inflammatory effect. However, the precise underlying mechanisms by which gut dysbiosis induces the development of arthritis remain elusive. This review aimed to highlight the mechanisms by which gut dysbiosis could contribute to the pathogenesis of RA. The overall data showed that gut dysbiosis could contribute to RA pathogenesis by multiple pathways, including alterations in gut barrier function, molecular mimicry, gut dysbiosis influences the activation and the differentiation of innate and acquired immune cells, cross-talk between gut microbiota-derived metabolites and immune cells, and alterations in the microenvironment. The relative weight of each of these mechanisms in RA pathogenesis remains uncertain. Recent studies showed a substantial role for gut microbiota-derived metabolites pathway, especially butyrate, in the RA pathogenesis.

Keywords: gut microflora; butyrate; gut microbiome; rheumatoid arthritis; short-chain fatty acid.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Mechanisms explained the relationship between intestinal dysbiosis and the development of rheumatoid arthritis.
Figure 2
Figure 2
Effect of intestinal dysbiosis on intestinal permeability and B and T cell polarization during the development of rheumatoid arthritis. Increased Zonulin secretion is followed by increased intestinal permeability (“leaky gut”) associated with the disassembly of ZO-1 protein from the tight junction complex. Bacteria or their components are transported to the joints via secondary lymphoid organs or the bloodstream. After encountering the microbiota-derivated antigen presented by antigen-presenting cells (APCs), naive CD4+ T cells differentiate into various subsets, including at least Th1, Th17, and Tfh cells.
Figure 3
Figure 3
Pleiotropic immunomodulatory effect of butyrate.
See this image and copyright information in PMC

References

    1. Aa L. X., Fei F., Qi Q., Sun R. B., Gu S. H., Di Z. Z., et al. (2020). Rebalancing of the gut flora and microbial metabolism is responsible for the anti-arthritis effect of kaempferol. Acta Pharmacol. Sin. 41 (1), 73–81. doi: 10.1038/s41401-019-0279-8 - DOI - PMC - PubMed
    1. Alameddine J., Godefroy E., Papargyris L., Sarrabayrouse G., Tabiasco J., Bridonneau C., et al. (2019). Faecalibacterium prausnitzii skews human DC to prime IL10-producing T cells through TLR2/6/JNK signaling and IL-10, IL-27, CD39, and IDO-1 induction. Front. Immunol. 10. doi: 10.3389/fimmu.2019.00143 - DOI - PMC - PubMed
    1. Amdekar S., Singh V., Kumar A., Sharma P., Singh R. (2013). Lactobacillus casei and lactobacillus acidophilus regulate inflammatory pathway and improve antioxidant status in collagen-induced arthritic rats. J. Interferon Cytokine Res. 33 (1), 1–8. doi: 10.1089/jir.2012.0034 - DOI - PubMed
    1. Audo R., Sanchez P., Riviere B., Mielle J., Tan J., Lukas C., et al. (2022). Rheumatoid arthritis is associated with increased gut permeability and bacterial translocation which are reversed by inflammation control. Rheumatol. (Oxford). doi: 10.1093/rheumatology/keac454 - DOI - PubMed
    1. Berthelot J. M., Sellam J., Maugars Y., Berenbaum F. (2019). Cartilage-gut-microbiome axis: a new paradigm for novel therapeutic opportunities in osteoarthritis. RMD Open 5 (2), e001037. doi: 10.1136/rmdopen-2019-001037 - DOI - PMC - PubMed