Functional characterization and directed modulation of the skin microbiome in pemphigoid diseases

类天疱疮疾病中皮肤微生物组的功能特征和定向调节

• 批准号: 279184070
• 负责人: Professor Dr. John F. Baines
• 金额: --
• 依托单位: Institut für Experimentelle Medizin (IEM)
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/279184070?language=en
• 关键词: Functional; characterization; directed; modulation; skin

The skin microbiota play an increasingly recognized role in immunity and local inflammatory responses, and alternations in these microbial communities are observed in the context of chronic inflammatory skin diseases. During the first funding period we achieved a thorough description of the skin microbiota in the context of bullous pemphigoid (BP) and identified several interesting candidate bacterial taxa that may influence the likelihood of disease emergence and/or severity. In this proposal, we aim to further characterize and test candidate probiotic bacteria and their products for the potential to modulate BP. Accordingly, we plan to achieve a fine-scale taxonomic and functional characterization of the skin microbiome in BP, including functional shotgun metagenomic profiling and experimental evaluation of the identified candidate bacteria in the context of mouse models of pemphigoid disease (PD). Candidate bacterial taxa belonging to the genera Staphylococcus and Propionibacterium are of specific interest, for which short chain fatty acids are candidate bacteria-derived effector molecules modulating disease. The specific aims of our proposal include (i) define species level taxonomy of key candidate indicator species, (ii) determine the effect of candidate probiotic bacteria in a mouse PD model and (iii) identify functional genomic differences and strain level variation in the human BP skin microbiome.

皮肤微生物群在免疫和局部炎症反应中发挥着越来越多的作用，在慢性炎症性皮肤病的背景下观察到这些微生物群落的变化。在第一个资助期内，我们在大疱性类天疱疮（BP）的背景下对皮肤微生物群进行了全面描述，并确定了几种可能影响疾病出现和/或严重程度的有趣的候选细菌分类群。在这项提案中，我们的目标是进一步表征和测试候选益生菌及其产品调节BP的潜力。因此，我们计划对BP中的皮肤微生物组进行精细的分类和功能表征，包括在类天疱疮疾病（PD）小鼠模型的背景下对所识别的候选细菌进行功能性鸟枪宏基因组分析和实验评估。属于葡萄球菌属和丙酸杆菌属的候选细菌分类群是特别感兴趣的，其中短链脂肪酸是调节疾病的候选细菌衍生的效应分子。我们提案的具体目标包括：（i）定义关键候选指示物种的物种水平分类法，（ii）确定候选益生菌在小鼠PD模型中的作用，以及（iii）确定人类BP皮肤微生物组中的功能基因组差异和菌株水平变异。