Determinants of the periocular microbiome

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PROJECT SUMMARY/ABSTRACT The microbiome of the eye and adnexal structures has not been well-characterized to date. The periocular eyelid margin has a substantial microbiome, and may be involved in disease states including blepharitis, Meibomian gland disease, dry eye syndrome, hordeolum, and chalazion. Preliminary data from our group suggest that, while the lid margin microbiome is relatively consistent between eyes and across time in individuals, there is substantial variation between individuals. The full extent of variability and the causes for these differences are not known. We propose studying the well-characterized, healthy TwinsUK cohort. This long-standing registry includes over 11,000 mono- and di-zygotic twins in the United Kingdom. Subjects will be recruited from this group, with all subjects completing questionnaires, having an ocular surface examination, and allowing a lid-margin swab to be obtained. DNA and RNA will be extracted and subjected to state-of-the-art metagenomic sequencing, with rigorous positive and negative controls. In the first aim, we will characterize the lid margin microbiome in this cohort. A subset of subjects will be sampled bilaterally and a subset longitudinally to determine the consistency and stability of findings. In the second aim, we will take advantage of the pre-existing large genomics database on these subjects to determine the heritability of the periocular microbiome and attempt to identify the genetic determinants of specific profiles. In the third aim, we will utilize both sampling of unrelated cohabitants as well as extensive pre-existing demographic, nutritional, and environmental data on this cohort to attempt to identify the environmental factors influencing the periocular microbiome. At the conclusion of this study we anticipate having generated the definitive catalogue of lid margin flora (including viruses and phage); and having established the genetic and environmental factors giving rise to specific microbial communities. All data will be made publicly available. These data will inform future studies on the relationship between ocular adnexal microbiome, eye disease, and specific interventions.