Evaluation of the cutaneous microbiome in psoriasis

银屑病皮肤微生物群的评估

• 批准号: 8698894
• 负责人: MARTIN J BLASER
• 金额: $ 18.75万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-12-05 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8698894
• 关键词: Affect; Area; Bacteria; Characteristics; Chronic; Clinical; Communities; Complex; Cutaneous; Data; Development; Disease; Ecosystem; Etiology; Evaluation; Failure; Gene Expression Profile; Genes; Genomics; Health; High-Throughput Nucleotide Sequencing; Immunologics; Individual; Inflammatory; Informatics; Learning; Lesion; Massive Parallel Sequencing; Methods; Microbiology; Molecular; Pathogenesis; Pathway Analysis; Pathway interactions; Patients; Persons; Phylogenetic Analysis; Play; Process; Proteins; Psoriasis; Relative (related person); Research; Ribosomal RNA; Role; Secondary to; Skin; Techniques; Testing; Time; Tissues; Treatment outcome; Variant; adalimumab; effective therapy; fungus; human disease; metagenome; metagenomic sequencing; microbial; microbiome; response; standard of care; success; tool

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.

描述（由申请方提供）：银屑病是一种病因不明的人类高度流行疾病，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，银屑病的皮肤微生物组很复杂，可能与正常情况不同。为了处理这种复杂性，我们建议在几个分类学和信息学水平上探索与银屑病相关的皮肤微生物组。我们的总体目标是研究正常皮肤微生物组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难以证明，并且超出了本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中观察到的范围相比，银屑病影响的皮肤区域的皮肤微生物组发生了变化。我们还假设微生物组的特征可能会影响对用于治疗银屑病的免疫调节剂的临床反应。另一种假设是，用全身免疫调节剂有效治疗银屑病不会对紊乱的微生物生态系统产生实质性影响。这些观察结果将为微生物群在这种疾病中的作用提供证据。由于微生物组研究中的一个重要考虑因素是检查科学问题的最佳水平（例如门，属，种，株，基因），我们还不确定牛皮癣的最佳水平是什么，这也将被检查。我们对银屑病的研究应该允许开发对微生物组研究具有普遍效用的方法和工具。为了验证我们的假设，我们提出了以下具体目标：1。了解覆盖银屑病病变的皮肤微生物组物种组成; 2.研究银屑病皮损与正常皮肤宏基因组含量的差异。使用高通量测序鉴定正常皮肤和银屑病病变之间微生物组和宿主的转录谱的差异;和4.评估银屑病全身免疫调节治疗对微生物组组成的影响。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：这是一个利用分子和基因组方法了解银屑病微生物学的项目。我们将比较银屑病患者和健康人，以了解他们之间皮肤上的微生物种类，基因和基因产物的差异。

项目成果

Body Site Is a More Determinant Factor than Human Population Diversity in the Healthy Skin Microbiome.

• DOI: 10.1371/journal.pone.0151990
• 发表时间: 2016
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Perez Perez GI;Gao Z;Jourdain R;Ramirez J;Gany F;Clavaud C;Demaude J;Breton L;Blaser MJ
• 通讯作者: Blaser MJ

A brave new world: the lung microbiota in an era of change.

• DOI: 10.1513/annalsats.201306-189mg
• 发表时间: 2014-01-01
• 期刊: Annals of the American Thoracic Society
• 影响因子: 8.3
• 作者: Segal, Leopoldo N;Blaser, Martin J
• 通讯作者: Blaser, Martin J

Microbiomic signatures of psoriasis: feasibility and methodology comparison.

• DOI: 10.1038/srep02620
• 发表时间: 2013
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Statnikov A;Alekseyenko AV;Li Z;Henaff M;Perez-Perez GI;Blaser MJ;Aliferis CF
• 通讯作者: Aliferis CF