Determinants of the periocular microbiome

项目概要/摘要 迄今为止，眼睛和附件结构的微生物组尚未得到充分表征。眼周眼睑 边缘具有大量的微生物组，并且可能涉及疾病状态，包括睑缘炎、睑板炎、结膜炎和结膜炎。 腺体疾病、干眼综合征、麦粒肿和睑板腺囊肿。我们小组的初步数据表明， 虽然眼睑边缘微生物组在个体的眼睛之间和时间上相对一致， 个体之间的巨大差异。变化的全部范围和这些差异的原因是 不知道。 我们建议研究特征良好的健康TwinsUK队列。这一长期登记册包括超过 英国有11,000对单卵双胞胎受试者将从该组招募，所有 受试者完成问卷调查，进行眼表检查，并允许眼睑边缘拭子 得到了DNA和RNA将被提取并进行最先进的宏基因组测序， 严格的阳性和阴性对照。在第一个目标中，我们将在本研究中表征眼睑边缘微生物组。 队列。将对一个受试者子集进行双侧采样，并对一个子集进行纵向采样，以确定一致性 和调查结果的稳定性。在第二个目标中，我们将利用现有的大型基因组数据库 以确定眼周微生物组的遗传性，并试图确定遗传因素。 特定轮廓的决定因素。在第三个目标中，我们也将利用不相关的同居者的抽样 作为关于该队列的广泛的预先存在的人口统计学、营养和环境数据， 影响眼周微生物组的环境因素。 在这项研究的结论，我们预计已产生了明确的目录眼睑边缘植物群 （包括病毒和噬菌体）;并确定了引起 特定的微生物群落。所有数据都将公开提供。这些数据将为未来的研究提供信息 关于眼附属器微生物组、眼部疾病和特定干预措施之间的关系。

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.