Putative Pathobionts in HLA-B27-Associated Spondyloarthropathy

Area of Science:

• Immunology
• Microbiology
• Genetics

Background:

• Spondyloarthritis (SpA) is an immune-mediated inflammatory disease strongly associated with HLA-B27.
• The exact mechanisms linking HLA-B27 to SpA pathogenesis remain elusive despite decades of research.
• Existing hypotheses involving arthritogenic peptides, endoplasmic reticulum stress, and NK cell targeting do not fully explain disease development.

Purpose of the Study:

• To review the role of microbial pathogenesis in HLA-B27-associated SpA.
• To explore whether specific pathobionts or broader microbial community disruptions drive SpA.
• To examine the potential of microbial functions and therapeutic interventions in SpA.

Main Methods:

• Analysis of evidence from animal models of SpA, including germ-free and colonized systems.
• Review of next-generation sequencing data characterizing gut microbial communities.
• Examination of proposed causal mechanisms like mucin degradation and gut barrier disruption.

Main Results:

• Germ-free environments prevent SpA development in animal models, which can be restored by gut commensal microbes.
• Gut microbial communities, their functions, and specific pathobionts are implicated in HLA-B27-associated SpA.
• Mechanisms include pathobiont effects on mucin degradation, mucosal adherence, and gut epithelial barrier integrity.

Conclusions:

• Microbial factors, particularly the functional capacity of the gut microbiome, play a significant role in HLA-B27-associated SpA.
• Understanding complex host-microbe interactions is key to developing novel therapeutic strategies.
• Therapeutic modalities like pre/probiotics, diet, and fecal microbiota transplantation show promise for SpA treatment.