Determinants of the periocular microbiome

项目摘要/摘要 到目前为止，眼睛和附件结构的微生物组还没有得到很好的描述。眼周眼睑 边缘有大量的微生物群，并可能参与包括眼缘炎、眉毛在内的疾病状态 腺病、干眼综合征、大疱性角质炎和雀斑疙瘩。我们小组的初步数据表明， 虽然眼睑边缘的微生物群在眼睛之间和个体之间相对一致，但有 个体之间有很大的差异。差异的全部范围和这些差异的原因如下 不知道。 我们建议研究特征良好、健康的TwinsUK队列。这一长期存在的注册表包括超过 英国有11000对同卵和双卵双胞胎。受试者将从这个小组中招募，所有 受试者完成问卷，进行眼表检查，并允许眼睑边缘拭子 获得。DNA和RNA将被提取并接受最先进的元基因组测序， 严格的正反两方面控制。在第一个目标中，我们将描述这个盖子边缘的微生物群 一群人。将对受试者的子集进行双边抽样，并对子集进行纵向抽样，以确定一致性 以及调查结果的稳定性。在第二个目标中，我们将利用现有的大型基因组数据库 对这些受试者确定眼周微生物组的遗传力，并试图确定 特定配置文件的决定因素。在第三个目标中，我们还将利用两个不相关同居者的样本 作为关于这个队列的大量先前存在的人口、营养和环境数据来尝试确定 影响眼周微生物群的环境因素。 在这项研究的结论中，我们预计已经生成了盖子边缘植物群的最终目录 (包括病毒和噬菌体)；以及确定了引起 特定的微生物群落。所有数据都将向公众开放。这些数据将为未来的研究提供信息 眼附属物微生物群与眼部疾病及特定干预措施的关系。

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.