The role of the gut microbiome on the development of ophthalmic diseases
The human gut microbiome performs a mutual relationship with the host’s immune system to maintain the intestinal homeostasis and to inhibit inflammatory processes. Applying whole-metagenome shotgun sequencing, we showed that dysbiosis may be involved in the development and / or progression of several eye diseases such as age-related macular degeneration, retinal artery occlusion, central serous chorioretinopathy and uveitis. Although it is still unknown how microbes and their metabolites exactly trigger the pathogenesis, associations between diseases and compositional as well as associated functional features of the gut microbiome provide the basis for targeted microbiome-altering interventions.
Characterization of the human ocular surface microbiome
Although the ocular surface is continuously exposed to the environment including a variety of microbes, the ocular microbiota has not been characterized in the Human Microbiome Project. In the 1930’s, a bacterial colonization of the conjunctiva in healthy human subjects has been described. With the introduction of modern sequencing technologies, a more in-depth characterization of the ocular surface microbiota has been achieved. Applying whole-metagenome sequencing, we succeeded in a taxonomic and functional characterization of the ocular surface microbiota. In addition, we defined the human tear proteome by tandem chromatography mass spectrometry and are performing association studies between the two systems in order to provide a comprehensive list of microbes and their functional profiles and metabolites for biomarker research of associated diseases.
Establishment of a gnotobiotic mouse model for ocular surface microbiome research
While sequencing methods have been effective in characterizing microbial communities in large biomass samples such as the gut, data inconsistencies pose a problem in low microbial niches such as the ocular surface. Although mouse models with stable, defined gut microbiota function in the absence of non-standardized confounding factors and are widely used by researchers in the field of host-microbiome interactions, they have not been established for ocular surface microbiome. We are establishing an unique gnotobiotic mouse model allowing standardized research of the microbiome of the healthy eye. This model can be applied to the development of microbiota-based therapeutic approaches for the treatment of several eye diseases.
