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

This study aims to explore the enteric virome characteristics of Vogt Koyanagi Harada (VKH) disease and its potential role in this disease.

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).

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.

The gut virome of patients with VKH differs significantly from healthy controls, suggesting its disturbance may contribute to gut microbiome imbalance and VKH development.