Evaluation of the cutaneous microbiome in psoriasis

描述(申请人提供)：牛皮癣是一种原因不明的人类高度流行的疾病，是一种主要累及皮肤的慢性炎症性疾病，具有独特的临床特征。随着新开发的促进微生物组研究的工具，现在可以评估皮肤微生物组是否在这种疾病的发病机制中发挥作用。我们研究的初步数据表明，银屑病患者的皮肤微生物群是复杂的，可能与正常不同。为了应对这种复杂性，我们建议通过几个分类学和信息学水平的探索来检查与银屑病有关的皮肤微生物组。我们的总体目标是研究正常皮肤微生物群的变化如何有助于银屑病的发病机制。由于因果关系复杂且通常很难证明，而且超出了这一RFP的范围，我们的总体假设是，与临床未受影响的区域或健康人观察到的范围相比，银屑病影响的皮肤区域的皮肤微生物群存在变化。我们还假设，微生物组的特征可能会影响临床对用于治疗牛皮癣的免疫调节剂的反应。另一种假说是，用全身性免疫调节剂有效治疗牛皮癣不会对紊乱的微生物生态系统产生实质性影响。这样的观察将为微生物区系在这种疾病中的作用提供证据。由于微生物组研究的一个重要考虑是检查科学问题的最佳水平(如门、属、种、菌株、基因)，而我们还不确定银屑病的最佳水平，因此也将对此进行检查。我们对牛皮癣的研究应该允许开发对微生物组研究具有普遍实用价值的方法和工具。为了验证我们的假设，我们提出了以下具体目标：1.了解覆盖在银屑病皮损上的皮肤微生物组的种类组成；2.调查银屑病皮损与正常皮肤之间元基因组含量的差异；3.利用高通量测序技术确定正常皮肤和银屑病皮损之间微生物组和宿主转录谱的差异；以及4.评估全身免疫调节治疗对银屑病微生物群组成的影响。总之，这些研究应该有助于我们了解微生物组在银屑病发病机制中的作用。公共卫生相关性：这是一个使用分子和基因组方法了解牛皮癣微生物学的项目。我们将比较银屑病患者和健康人，以了解他们之间不同的微生物种类、基因和皮肤上的基因产物。

DESCRIPTION (provided by the applicant): Psoriasis, a highly prevalent disease of humans of unknown cause, is a chronic inflammatory disorder primarily involving skin, with distinctive clinical characteristics. With the newly developed tools that facilitate microbiome research, it now is possible to assess whether the cutaneous microbiome plays a role in the pathogenesis of this disorder. Preliminary data from our studies suggest that the cutaneous microbiome in psoriasis is complex and possibly different from normal. To deal with this complexity, we propose to examine the cutaneous microbiome in relation to psoriasis with explorations at several taxonomic and informatic levels. Our overall objective is to examine how changes in the normal cutaneous microbiome contribute to the pathogenesis of psoriasis. Since causality is complex and often difficult to prove, and beyond the scope of this RFP, our overall hypothesis is that there are alterations in the cutaneous microbiome in areas of skin affected by psoriasis in comparison with the range observed in clinically unaffected areas, or in healthy persons. We also hypothesize that the characteristics of the microbiome may affect clinical responses to the immunomodulatory agents used to treat psoriasis. An alternative hypothesis is that effective treatment of psoriasis with systemic immunomodulatory agents will not substantially affect the disordered microbial ecosystem. Such observations would provide evidence for the roles of the microbiota in this disorder. Since an important consideration in microbiome research is the optimal level (e.g. phylum, genus, species, strain, gene) at which to examine a scientific question, and we are not yet certain what are the optimal levels for psoriasis, this also will be examined. Our studies of psoriasis should allow development of both approaches and tools that will have general utility for microbiome research. To test our hypothesis, we propose the following specific aims: 1. To understand the cutaneous microbiome species composition overlaying psoriatic lesions; 2. To investigate differences in metagenome content for psoriatic lesions compared to normal skin; 3. To identify differences in the transcriptional profiles of the microbiome and the host between normal skin and psoriatic lesions using high-throughput sequencing; and 4. To estimate the effects of systemic immunomodulatory therapy for psoriasis on microbiome composition. In total, these studies should help us understand the role of the microbiome in psoriasis pathogenesis. PUBLIC HEALTH RELEVANCE: This is a project to understand the microbiology of psoriasis using molecular and genomic methods. We will compare patients with psoriasis and healthy individuals to learn the microbial species, genes, and gene products on the skin that differ between them.