Microbiome signatures and their role in uveitis: Pathogenesis, diagnostics, and therapeutic perspectives

Abstract

Non-infectious uveitis is a group of complex inflammatory eye diseases shaped by genetic susceptibility, immune dysregulation, and environmental cues. Among these, the mucosal microbiome—including gut, oral, and ocular surface microbial communities—has emerged as a key player in modulating systemic and ocular immune responses. Recent evidence supports a gut-eye axis wherein microbial dysbiosis alters intestinal barrier function, perturbs T cell homeostasis, and drives systemic immune activation that can breach ocular immune privilege. Specific taxa, such as Prevotella and Faecalibacterium, as well as microbial metabolites including short-chain fatty acids, have been implicated in promoting or mitigating ocular inflammation. Human leukocyte antigen (HLA) alleles, notably HLA-B27 and HLA-A29, influence both microbiome composition and disease phenotype, suggesting a gene–microbiome–immunity triad of interaction in uveitis pathogenesis. Drawing on insights from metagenomics, metabolomics, in vitro and in vivo experimental and murine models, this review delineates four key mechanisms—immune imbalance, antigenic mimicry, epithelial barrier disruption, and bacterial translocation—that underpin the key roles of microbiome in uveitis. We combine current literature and integrate findings from our research programs to highlight diagnostic and therapeutic opportunities. Microbiome-informed strategies, such as rational probiotic design, dietary modulation, and targeted microbial therapies, hold promise for complementing existing immunosuppressive regimens. Translating these insights into clinical practice requires robust multi-omic studies, longitudinal cohorts, mechanistic studies, and precision-guided intervention trials. By framing uveitis within a mucosal immunological context, this review proposes a future precision medicine roadmap for integrating microbiome science into ocular inflammatory disease management.