The microbiome in HLA-B27-associated disease: implications for acute anterior uveitis and recommendations for future studies.

The pathogenesis of human leukocyte antigen (HLA)-B27-associated diseases such as acute anterior uveitis (AAU) and ankylosing spondylitis (AS) remains poorly understood, though Gram-negative bacteria and subclinical bowel inflammation are strongly implicated. Accumulating evidence from animal models and clinical studies supports several hypotheses, including HLA-B27-dependent dysbiosis, altered intestinal permeability, and molecular mimicry. However, the existing literature is hampered by inadequate studies designed to establish causation or uncover the role of viruses and fungi. Moreover, the unique disease model afforded by AAU to study the gut microbiota has been neglected. This review critically evaluates the current literature and prevailing hypotheses on the link between the gut microbiota and HLA-B27-associated disease. We propose a new potential role for HLA-B27-driven altered antibody responses to gut microbiota in disease pathogenesis and outline recommendations for future well-controlled human studies, focusing on AAU. Emerging human and animal studies of human leukocyte antigen (HLA)-B27-associated diseases have led to the development of several hypotheses for how HLA-B27 can influence the composition and function of the gut microbiota to mediate its disease associations. Shared metabolic dysregulations, despite the heterogenous taxa signatures observed, may underpin how the microbiome contributes to HLA-B27-associated disease, but it remains unclear if dysbiosis is directly driving disease. HLA-B27 transgenic rats that develop a spontaneous spondyloarthropathy-like illness do not develop disease when raised in a germ-free environment, but mono-association with Phocaeicola vulgatus is sufficient to induce disease. Progress in the field has been relatively slow due to the lack of integration between human studies and available animal models of disease, and increased attention should be paid to the microbiome in HLA-B27-associated acute anterior uveitis. [ABSTRACT FROM AUTHOR]