Population dynamics of P. acnes and their phages in the human skin microbiome

人类皮肤微生物组中痤疮丙酸杆菌及其噬菌体的种群动态

• 批准号: 8212611
• 负责人: Huiying Li
• 金额: $ 35.53万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-05 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8212611
• 关键词: Acne; Acne Vulgaris; Address; Affect; Aftercare; Age; American; Antibiotic Therapy; Bacteriophages; Cicatrix; Clinical; Color; Communities; Complex; Cutaneous; Data; Development; Disease; Dizygotic Twins; Environment; Etiology; Funding; Gene Expression Profile; Genetic; Goals; Hair follicle structure; Health; Human; Human Microbiome; Immune response; Immune system; Immunity; Immunohistochemistry; Individual; Knowledge; Lead; Left; Medical; Microbe; Modeling; Monozygotic twins; Pathogenesis; Patients; Play; Population; Population Dynamics; Propionibacterium acnes; Recombinant DNA; Relative (related person); Ribotypes; Ribotyping; Role; Sampling; Site; Skin; Skin Physiology; Skin Tissue; Specificity; Structure; Surface; System; Testing; Therapeutic; Time; United States National Institutes of Health; Whole-Genome Shotgun Sequencing; base; innovation; metagenomic sequencing; microbial; microbial community; microbiome; pathogen; prevent; skin disorder; success; treatment strategy

DESCRIPTION (provided by applicant): The human skin microbiota is complex and dynamic. It plays a significant role in defending against pathogens by interacting with the host immune system. To understand the dynamics of the skin microbial community and the effect on the human health upon its perturbation, we propose to study the population dynamics of a major skin commensal, Propionibacterium acnes, and its phages in pilosebaceous units (hair follicles). One of the diseases associated with pilosebaceous units is acne. Acne is one of the most common skin diseases. Although its etiology still needs to be defined, a bacterial factor has been suggested in the development of the disease. In fact, antibiotic therapy targeting P. acnes has been a mainstay treatment for more than 30 years. Our preliminary study shows that microcomedone, a specialized skin compartment where acne arises, has a tractable microbiome with a single dominant species, P. acnes. This system offers a unique advantage allowing in-depth analysis of a human microbiome and its dynamics at the subspecies/population level. Previously, by 16S rDNA analysis, we found that certain P. acnes ribotypes are highly enriched in acne, and in contrast, certain ribotype is over-represented in healthy skin. This indicates that studying the structure and dynamics of the microbial community offers promise for understanding the correlation between the microbial community and human health and disease. In this project, we plan to investigate in three directions the dynamics of th microbiome in pilosebaceous units. First, we plan to define the population structure and dynamics of P. acnes in microcomedones and examine whether they are different in health and acne. Second, we plan to determine whether predator-prey population dynamics exist between P. acnes and P. acnes phages and whether the dynamics are different in health and acne. Third, we will examine the interactions between the microbes and the host by transcriptional profiling of both the microbiota and the host and determine whether changes in the microbial community alter the host immune responses. This proposed study will define the population structure and dynamics of P. acnes and its phages in the pilosebaceous units of healthy individuals and acne patients and their interactions with the host. The findings from the study will address a fundamental gap in our knowledge of the skin microbiome and may lead to further studies for the development of innovative clinical approaches to treating, preventing and managing the disease. PUBLIC HEALTH RELEVANCE: Human skin provides the first line of defense against pathogens. The goal of this project is to investigate the dynamics of the microbial community residing underneath the surface of human skin and its association with acne, a common skin disease affecting 17 million Americans; more than 80% of the people of age 12-24. Success in this project may lead to the development of new effective therapeutic strategies for treatment of acne.

描述（由申请人提供）：人体皮肤微生物群是复杂和动态的。它通过与宿主免疫系统相互作用，在抵御病原体方面发挥着重要作用。为了了解皮肤微生物群落的动态及其扰动对人类健康的影响，我们建议研究一种主要的皮肤共生菌痤疮丙酸杆菌及其在毛囊中的噬菌体的种群动态。与皮脂腺单位相关的疾病之一是痤疮。痤疮是最常见的皮肤病之一。虽然其病因仍需明确，但细菌因素已被认为在疾病的发展。事实上，针对痤疮P.的抗生素治疗已经成为30多年来的主要治疗方法。我们的初步研究表明，微粉刺，一个特殊的皮肤隔间，痤疮产生，有一个单一的优势种，痤疮P.易处理的微生物组。该系统提供了一个独特的优势，允许在亚种/种群水平上深入分析人类微生物组及其动态。先前，通过16S rDNA分析，我们发现痤疮中某些核糖型高度富集，相反，某些核糖型在健康皮肤中过度代表。这表明，研究微生物群落的结构和动态为理解微生物群落与人类健康和疾病之间的关系提供了希望。在本项目中，我们计划从三个方向研究毛囊皮脂腺单位微生物组的动态。首先，我们计划确定微型粉刺中痤疮P.的种群结构和动态，并检查它们在健康和痤疮中是否不同。其次，我们计划确定痤疮假单胞杆菌和痤疮假单胞杆菌噬菌体之间是否存在捕食者-猎物种群动态，以及健康和痤疮的动态是否不同。第三，我们将通过微生物群和宿主的转录谱来研究微生物和宿主之间的相互作用，并确定微生物群落的变化是否会改变宿主的免疫反应。本研究将确定健康个体和痤疮患者皮脂腺单位中痤疮假单胞菌及其噬菌体的种群结构和动态，以及它们与宿主的相互作用。这项研究的发现将解决我们对皮肤微生物群知识的根本空白，并可能导致进一步的研究，以开发治疗、预防和管理这种疾病的创新临床方法。