Alterations of the Enteric Virome in Vogt-Koyanagi-Harada Disease.

Purpose: This study aims to explore the enteric virome characteristics of Vogt Koyanagi Harada (VKH) disease and its potential role in this disease. Methods: Shotgun metagenomic sequencing was used to detect the enteric virome and 16S rRNA to detect the bacteriome in new-onset, untreated patients with VKH (n = 25) and age- and sex-matched healthy controls without autoimmune diseases (n = 25). Results: Patients with VKH exhibited different enteric viral communities from healthy controls, characterized by decreased richness of core viral communities (present in > 80% of samples) and increased richness of common viral communities (present in 50%-80% of samples). Notably, within the core virus community, bacteriophage richness was markedly reduced, whereas eukaryotic virus richness significantly increased in patients with VKH. The case-control analysis identified 42 differentially abundant viruses, including a decrease in crAss-like phages, the eukaryotic virus Moumouvirus_moumou, and an enrichment of the Chlamydiamicrovirus_CPG1. Most of the differential phages predominantly targeted bacteria from the phyla Pseudomonadota and Firmicutes. The gut virome-bacteria community correlation analysis revealed a shift in the interactions between the core viruses and bacterial communities. Additionally, Wroclawvirus PA5oct (a Pseudomonas phage) correlated with leukotrichia, a clinically relevant symptom of VKH (P = 0.042). The impact of multiple Pseudomonas phages on the host folate biosynthesis was significantly enhanced in patients with VKH. Moreover, the protein (Earp361-372) encoded by VKH-enriched Pseudomonas was identified to share homology with the melanin antigen gp10044-59. Conclusions: The gut virome of patients with VKH differs significantly from healthy controls, suggesting its disturbance may contribute to gut microbiome imbalance and VKH development.