Oral administration of probiotic Limosilactobacillus reuteri DSM 17938 suppresses dry eye disease in the desiccating stress mouse model.

PURPOSE: Gut dysbiosis can adversely affect the ocular surface, resulting in inflammation and dry eye. We investigated the potential of an orally administered probiotic bacteria, Limosilactobacillus reuteri DSM17938 (LR17938), on dry eye disease in the desiccating stress (DS) mouse model. METHODS: C57BL/6J mice were treated with antibiotics (ABX) to induce dysbiosis; stools were analyzed using 16S sequencing. Mice were subjected to 5 days DS while receiving daily gavage of PBS or LR17938. Conjunctival goblet cell (GC) density was assessed in formalin-fixed histological sections. Corneal barrier function was evaluated by Oregon-Green-Dextran dye uptake. T-cells were assessed by flow cytometry. MMP-9 was visualized in corneal epithelium with immunofluorescence. LR17938 efficacy was tested in the context of human gut microbiota by using mice colonized with fecal microbes from Sjögren's disease (SjD) or healthy patients. Metagenomic sequencing was performed on stool collected before and after DS. RESULTS: 16S sequencing confirmed profound intestinal dysbiosis after ABX treatment. LR17938 administration in ABX-treated mice exposed to DS improved corneal barrier function, preserved GC density, reduced MMP-9 in corneal epithelium, increased T-regulatory cells and decreased inflammatory T-cells in cervical lymph nodes. In mice colonized with human microbiota, treatment improved corneal barrier function and GC number regardless of microbiota source. Microbiome differences were driven by SjD disease status regardless of DS exposure or probiotic treatment. While DS caused minor shifts, probiotic treatment did not result in significant changes to the gut microbiome. CONCLUSIONS: LR17938 is a promising complementary treatment for dry eye, showing protective effects to the ocular surface.