Dysbiosis in Inflammatory Bowel Disease and Spondyloarthritis: Still a Long Way to Go?

Abstract

The association between Inflammatory Bowel Disease (IBD) and Spondyloarthritis (SpA) has been known for years, as has the concept that IBD is associated with an altered intestinal bacterial composition, a condition known as "dysbiosis". Recently, a state of intestinal dysbiosis has also been found in SpA. Dysbiosis in the field of IBD has been well characterized so far, as well as in SpA. The aim of this review is to summarize what is known to date and to emphasize the similarities between the microbiota conditions in these two diseases: particularly, an altered distribution in the gut of Enterobacteriaceae, Streptococcus, Haemophilus, Clostridium, Akkermansia, Ruminococcus, Faecalibacterium Prausnitzii, Bacteroides Vulgatus, Dialister Invisus, and Bifidubacterium Adolescentis is common to both IBD and SpA. At the same time, little is known about intestinal dysbiosis in IBD-related SpA. Only a single recent study has found an increase in Escherichia and Shigella abundances and a decrease in Firmicutes, Ruminococcaceae, and Faecalibacterium abundances in an IBD-related SpA group. Based on what has been discovered so far about the altered distribution of bacteria that unite both pathologies, it is appropriate to carry out further studies aiming to improve the understanding of IBD-related SpA for the purpose of developing new therapeutic strategies.

Keywords: dysbiosis; fecal microbiota transplantation; inflammatory bowel disease; microbiota; spondyloarthritis; tumor necrosis factor alpha inhibitor.

Figure 1

Three probable mechanisms that could explain the link between joint inflammation and the gut. First hypothesis: the surface molecule HLA-B27, interacting with the “arthritogenic peptide” in the gut, would lead to the activation of cytotoxic lymphocytes and NK cells whose activity would then be expressed in the joints (a). Second hypothesis: Activated T-cells in the gut overexpress adhesion molecules such as α4β7 integrin on their surface, which, through binding to MAdCAM, promotes T-cell homing in gut-associated lymphoid tissues. However, even in joints, the endothelium expresses MAdCAM, favoring T-cell homing there as well (b). Third hypothesis: exposure to large amounts of bacteria in the gut leads to the secretion of zonulin, which causes disassembly of the ZO-1 protein from the tight junction complex, resulting in increased intestinal permeability with an inability to prevent the translocation of bacteria and their products; this follows an activation of the immune system, which, therefore, would transmigrate from the intestine to the joints (c).

Figure 1

Three probable mechanisms that could explain the link between joint inflammation and the gut. First hypothesis: the surface molecule HLA-B27, interacting with the “arthritogenic peptide” in the gut, would lead to the activation of cytotoxic lymphocytes and NK cells whose activity would then be expressed in the joints (a). Second hypothesis: Activated T-cells in the gut overexpress adhesion molecules such as α4β7 integrin on their surface, which, through binding to MAdCAM, promotes T-cell homing in gut-associated lymphoid tissues. However, even in joints, the endothelium expresses MAdCAM, favoring T-cell homing there as well (b). Third hypothesis: exposure to large amounts of bacteria in the gut leads to the secretion of zonulin, which causes disassembly of the ZO-1 protein from the tight junction complex, resulting in increased intestinal permeability with an inability to prevent the translocation of bacteria and their products; this follows an activation of the immune system, which, therefore, would transmigrate from the intestine to the joints (c).