Helicobacter pylori Infection's Dual Impact on the Ocular Surface: Tear Secretion Disruption and Ocular Surface Microbiome Alteration.

Purpose: The purpose of this study was to investigate the impact of Helicobacter pylori (H. pylori) infection on ocular surface homeostasis, including dry eye symptoms, ocular microbiota alterations, and related immune responses. Methods: Thirty-one H. pylori-positive (Hp_pos) and 30 H. pylori-negative (Hp_neg) subjects underwent dry eye assessments, including the Schirmer I test, noninvasive keratography first and average breakup times (NIKf-BUTs and NIKav-BUTs), tear meniscus height, meibomian gland loss, and the Ocular Surface Disease Index (OSDI). Sterile swabs were used to collect samples from each eye of subjects for 16S rRNA sequencing. Additionally, a murine H. pylori infection model was established to evaluate dry eye phenotypes and immune responses in the lacrimal gland. Results: Compared with Hp_neg subjects, Hp_pos subjects showed significantly reduced Schirmer I test results, NIKf-BUT, and NIKav-BUT, along with higher OSDI scores (all P < 0.05), whereas tear meniscus height and meibomian gland loss did not differ between the two groups. The ocular surface microbiota of Hp_pos subjects exhibited altered alpha and beta diversity, with 10 enriched genera (dominated by Veillonella and Capnocytophaga), which were characteristically associated with dry eye manifestations. In the murine model, infected mice at 6 weeks post-infection displayed aqueous tear deficiency, corneal epithelial barrier impairment, lacrimal gland infiltration of CD4+ and CD45+ T lymphocytes, and upregulated proinflammatory cytokines (IFN-γ, IL-17A, IL-4, TGF-β, TNFα, IL-6, and IL-1β). However, no significant differences were observed at 2 or 4 weeks post-infection. Conclusions: The H. pylori infection disrupts tear secretion and ocular surface microbiota, potentially via inducing T lymphocyte infiltration and lacrimal gland inflammation, contributing to dry eye pathogenesis.