Gut microbiome and plasma metabolome alterations in myopic mice.

Abstract

Myopia is one of the most common eye diseases leading to blurred distance vision. Inflammatory diseases could trigger or exacerbate myopic changes. Although gut microbiota bacteria are associated with various inflammatory diseases, little is known about its role in myopia. The mice were randomly divided into control and model groups, with the model group being attached-30D lens onto the eyes for 3 weeks. Then, mouse cecal contents and plasma were collected to analyze their intestinal microbiota and plasma metabolome. We identified that the microbial composition differed considerably between the myopic and non-myopic mice, with the relative abundance of Firmicutes phylum decreased obviously while that of Actinobacteria phylum was increased in myopia. Furthermore, Actinobacteria and Bifidobacterium were positively correlated with axial lengths (ALs) of eyeballs while negatively correlated with refractive diopters. Untargeted metabolomic analysis identified 141 differentially expressed metabolites, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed considerable enrichment mainly in amino acid metabolism pathways. Notably, pathways involved glutamate metabolism including "Glutamine and D-glutamate metabolism" and "Alanine, aspartate and glutamate metabolism" was changed dramatically, which presented as the concentrations of L-Glutamate and L-Glutamine decreased obviously in myopia. Interestingly, microbiome dysbiosis and metabolites alternations in myopia have a disrupting gut barrier feature. We further demonstrated that the gut barrier function was impaired in myopic mice manifesting in decreased expression of Occludin, ZO-1 and increased permeation of FITC-dextran. Myopic mice had obviously altered gut microbiome and metabolites profiles compared to non-myopic mice. The dysbiosis and plasma metabolomics shift in myopia had an interrupting gut barrier feature. Our study provides new insights into the possible role of the gut microbiota in myopia and reinforces the potential feasibility of microbiome-based therapies in myopia.