The Landscape of Host-Microbiota Interactions at the Ocular Mucosa

Characterization of host-microbiota interactions at mucosal surfaces is essential for understanding the role of microbial dysbiosis in the pathogenesis of immune-mediated diseases. However, identifying the microbe-specific mucosal immune response in humans has challenges in distinguishing microorganisms that directly interact with the mucosa and capturing local host responses to them. Here, we performed a paralleled analysis on host gene expression and microbiota activity profiles of 436 conjunctival metatranscriptomes from 109 monozygotic twin pairs. Our within-twin-pair analysis revealed associations between the activity of microbial species and immune cells, cytokines, and human leukocyte antigens, while excluding the influence of host genetics and the environment . We further identified an association of Gordonia bronchialis with ocular graft-versus-host disease (GVHD) by surveying conjunctival metagenomes from 124 individuals and analyzed the putative role of this species in GVHD, demonstrating potential implications of the microbial species-specific human mucosal responses in investigating the etiology of immune-mediated diseases.