Metagenomic study of the human skin microbiome associated with acne

描述：人类微生物区系有助于我们正常的出生后发育，并在定义我们的生理学方面扮演着重要的角色。为了了解微生物区系在人类健康和疾病中的作用，我们建议研究毛皮脂腺单位(毛囊)中的皮肤微生物群及其与痤疮的关系。 粉刺是最常见的皮肤病之一。虽然其病因仍需确定，但细菌因素已被认为在疾病的发展中。事实上，针对痤疮丙酸杆菌的抗生素治疗已经是30多年来的主流治疗方法。 我们的初步研究表明，微粉刺是一种专门的皮肤隔膜，在那里会出现粉刺，它有一个易于驯服的微生物群，只有一个优势种，痤疮假单胞菌。这个系统提供了一个独特的优势，可以通过DNA测序在亚种水平上深入分析人类微生物群，而许多其他身体部位的微生物群落太复杂了，即使在物种水平上也无法分解。在我们的初步研究中，我们发现痤疮患者的痤疮假单胞菌菌株似乎是克隆性的，具有明显的16S rDNA序列的核苷酸特征，而正常人的痤疮假单胞菌菌株更加多样化，分散在许多谱系中。这表明，与痤疮相关的微生物组为了解微生物组的组成与人类健康和疾病之间的关系提供了希望。 在这个项目中，我们计划从三个方向调查与痤疮相关的微生物群。首先，我们计划调查痤疮假单胞菌在疾病队列和正常队列中的菌株多样性，并检查某些菌株是否与疾病相关。其次，我们计划调查非P。检测粉刺病原体和皮损中的粉刺微生物是否与粉刺发病机制相关。这些微生物包括小型真核生物、细菌、病毒和噬菌体。第三，我们将通过微生物区系和宿主的转录图谱来检查微生物和宿主之间的相互作用。到这个项目的第一年结束时，我们计划完成10,000个16S rDNA克隆和48个痤疮假单胞菌全基因组的测序。我们相信，我们对毛囊皮脂腺单位的微生物群的分析将有助于阐明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：粉刺影响了1700万美国人，占12-24岁人群的80%以上。该项目的目标是调查痤疮与人体皮肤表面下的微生物区系之间的关系。该项目的成功可能会导致开发治疗痤疮的新的有效治疗策略。

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.