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Metagenomic study of the human skin microbiome associated with acne

与痤疮相关的人类皮肤微生物组的宏基因组研究

基本信息

批准号：
8145521
负责人：
Huiying Li
金额：
$ 25万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-05-15 至 2012-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8145521
关键词：
Accounting Acne Acne Vulgaris Affect Age American Antibiotic Therapy Antibiotics Bacteria Bacteriophages Biota Clinical Complementarity Determining Regions Cutaneous DNA Sequence Data Development Disease Environment Enzyme-Linked Immunosorbent Assay Etiology Eukaryota Gene Expression Profile Genes Genetic Genetic Transcription Genome Goals Habitats Hair follicle structure Health Human Human Microbiome Human body Immune Immune response Individual Lead Lesion Light Mass Spectrum Analysis Measurement Metagenomics Microbe Nucleotides Pathogenesis Pathway interactions Patients Phenotype Physiology Play Propionibacterium acnes Recombinant DNA Relative (related person)Reverse Transcriptase Polymerase Chain Reaction Role Site Skin Skin Tissue Staging Surface System Therapeutic Virus base cohort fungus insight metagenomic sequencing microbial microbial community microbiome postnatal pre-clinical public health relevance skin disorder success therapeutic effectiveness treatment strategy

项目摘要

DESCRIPTION: The human microbiota contributes to our normal postnatal development and plays a significant role in defining our physiology. To understand the role of microbiota in human health and disease, we propose to study the skin microbiome in pilosebaceous units (hair follicles) and its association with 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 Propionibacterium acnes has been a mainstay treatment for more than 30 years. Our preliminary study shows that the 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 at the subspecies level by DNA sequencing, whereas the microbial communities at many other body sites are just too complicated to deconvolute even at the species level. In our preliminary study, we find that P. acnes strains in acne patients appear to be clonal, with distinct nucleotide signatures of 16S rDNA sequences, whereas P. acnes strains from normal individuals are much more diverse and scatter through many lineages. This indicates that the microbiome associated with acne offers promise for understanding the correlation between the composition of the microbiome and human health and disease. In this project, we plan to investigate in three directions the microbiome associated with acne. First, we plan to investigate the strain diversity of P. acnes in a disease cohort and normal cohort and examine whether certain strains of P. acnes are correlated with disease. Second, we plan to investigate the non-P. acnes microbes in microcomedones and disease lesions and examine whether they correlate with acne pathogenesis. These microbes include small eukaryotes, bacteria, viruses and bacteriophages. Third, we will examine the interactions between the microbes and the host by transcriptional profiling of both the microbiota and the host. By the end of the first year of this project, we plan to complete the sequencing of 10,000 16S rDNA clones and 48 full genomes of P. acnes strains. We believe our analysis of the microbiome of the pilosebaceous units will shed light on the microbial composition of the skin biota and its relation to acne. PUBLIC HEALTH RELEVANCE: Acne affects 17 million Americans, more than 80% of the people of age 12-24. The goal of this project is to investigate the relationship between acne and the microbiota residing underneath the surface of the human skin. Success in this project may lead to the development of new effective therapeutic strategies for treatment of acne.

描述：人体微生物群有助于我们正常的产后发育，并在定义我们的生理机能方面发挥重要作用。为了了解微生物群在人类健康和疾病中的作用，我们建议研究毛囊皮脂腺单位（毛囊）中的皮肤微生物组及其与痤疮的关系。痤疮是最常见的皮肤病之一。虽然其病因仍需确定，但已提出细菌因素在疾病的发展中。事实上，针对痤疮丙酸杆菌的抗生素治疗已成为30多年来的主要治疗方法。我们的初步研究表明，微粉刺，一个专门的皮肤隔间，痤疮出现，有一个易于处理的微生物组，具有单一的优势物种，痤疮丙酸杆菌。该系统提供了一个独特的优势，允许通过DNA测序在亚种水平上深入分析人类微生物组，而许多其他身体部位的微生物群落太复杂，即使在物种水平上也无法解卷积。在我们的初步研究中，我们发现痤疮患者中的痤疮丙酸杆菌菌株似乎是克隆的，具有不同的16 S rDNA序列的核苷酸特征，而来自正常个体的痤疮丙酸杆菌菌株更加多样化，分散在许多谱系中。这表明与痤疮相关的微生物组为理解微生物组组成与人类健康和疾病之间的相关性提供了希望。在这个项目中，我们计划从三个方向研究与痤疮相关的微生物组。首先，我们计划调查疾病队列和正常队列中痤疮丙酸杆菌的菌株多样性，并检查某些痤疮丙酸杆菌菌株是否与疾病相关。其次，我们计划研究痤疮微粉刺和疾病病变中的非痤疮丙酸杆菌微生物，并检查它们是否与痤疮发病机制相关。这些微生物包括小型真核生物、细菌、病毒和噬菌体。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。到本项目第一年结束时，我们计划完成10，000个16 S rDNA克隆和48个痤疮丙酸杆菌菌株全基因组的测序。我们相信我们对毛囊皮脂腺单位微生物组的分析将揭示皮肤生物群的微生物组成及其与痤疮的关系。公共卫生相关性：痤疮影响1700万美国人，占12-24岁人群的80%以上。该项目的目标是研究痤疮与人类皮肤表面下的微生物群之间的关系。该项目的成功可能会导致开发新的有效的治疗痤疮的治疗策略。