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.

Keywords: Dysbiosis; Gut microbiome; Ocular inflammation; Ocular surface microbiome; Oral microbiome; Uveitis.