Figure 3.

Pathobionts depend on host genetics and gut microbial community. The gut microbiota is highly diverse and varies between healthy individuals depending on host genetics, diet and environment. Each individual microbial community consists mostly of commensals which provide colonization resistance to opportunistic pathobionts. In genetically susceptible individuals (HLA-B27), there is microbial dysbiosis concomitant to loss of epithelial barrier resulting in an inflammatory microenvironment which further increases the loss in commensal microbes. This presents a unique opportunity for pathobionts to thrive and exacerbate inflammation. Since different individuals have different microbial community structure and different pathobionts depending on their genetics and environment, this may explain why we observe different pathobionts associated with various spondyloarthropathies. In microbial community A, only pathobiont A is present and when the conditions change (a trigger). In addition, certain pathobionts can make bactericidal compounds known as bacteriocins to avoids colonization resistance. When the pathobiont A is in bloom, it increases and exacerbates inflammation by degrading mucus and disrupting epithelial barrier. However, in another microbial community on a distinct host genetic background and in the presence of pathobiont B, which is mucous associated, an increased relative abundance can be associated with disease as most microbes are unable to cross the mucous barrier. In both cases, the dendritic cells (DCs) and Macrophages (Mφ) release inflammatory mediators such as IL-23, TNF-α, and IL-6, which activate T helper 17 cells to make IL-17, IL-22 causing inflammation and disrupting epithelial barrier thereby perpetuating the inflammatory cycle. Figure created with Biorender.com.