Comprehensive characterization of parasite and commensal assemblages in humans

人类寄生虫和共生组合的综合表征

• 批准号: 10554346
• 负责人: Tony L. Goldberg
• 金额: $ 19.44万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-24 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10554346
• 关键词: Affect; Animals; Antigens; Antiparasitic Agents; Bacteria; Bacteriology; Bar Codes; Bioinformatics; Biological Assay; Biology; Blood; Communities; Custom; DNA; DNA sequencing; Data; Data Analyses; Data Set; Databases; Detection; Development; Diagnostic; Digestion; Disadvantaged; Disease; Disease Outcome; Ecology; Equilibrium; Eukaryota; Formalin; Future; Goals; Health; Helminths; Human; Immunity; In Vitro; Industry Standard; Intestinal parasite; Knowledge; Lead; Literature; Medicine; Metagenomics; Methodology; Methods; Microscopic; Microscopy; Molecular; Morbidity - disease rate; Noise; Organism; Parasites; Parasitic Diseases; Parasitic infection; Parasitology; Pathogenicity; Performance; Persons; Play; Population; Predictive Value; Preparation; Process; Prokaryotic Cells; Protocols documentation; Protozoa; Publishing; Reagent; Research; Research Methodology; Resolution; Risk; Role; Sampling; Specificity; Standardization; Structure; Taxonomy; The science of Mycology; Therapeutic; Tissues; Virus; Work; analysis pipeline; bacterial community; bacteriome; bioinformatics pipeline; design; detection method; diagnostic tool; disorder risk; dysbiosis; fungal microbiota; fungus; high risk population; human disease; improved; in silico; insight; microbiome; mortality; mycobiome; novel; pathogen; prevent; symbiont; tool; user-friendly

PROJECT SUMMARY/ABSTRACT Diseases attributed to parasites cause substantial morbidity and mortality globally. However, there is mounting evidence that the relationship between humans and symbionts (defined here as all host-dependent eukaryotic organisms, including parasites and commensals) is not always detrimental and, in fact, may sometimes confer important health advantages. Symbiont assemblages may aid in digestion, confer protective immunity, or, paradoxically, provide protection from pathogenic parasite infection and disease. We currently understand the biology and ecology of eukaryotic parasites that cause human disease, but we know very little about the overall structure and function of communities of protozoans and helminths that also colonize humans. This shortcoming hinders progress in the field of parasitology, compared to the fields of bacteriology and mycology, which have revolutionized our understanding of human health through the study of bacterial and fungal microbiota. Indeed, most current parasitological methods are designed for a different purpose: to target specific, pathogenic organisms. Although methods for unbiased community analysis have been validated and standardized for prokaryotes and fungi, no such methods currently exist for eukaryotic symbionts, including parasites. With no standardized methods in place, research into the beneficial effects of eukaryotic symbiont communities and their potential role in parasitic disease represents a critical knowledge gap. The ultimate objective of this work is to create a uniform, validated research tool for the study of human symbiont assemblages, comparable to what has been achieved for the bacterial and fungal microbiomes. To this end, we have developed a novel comprehensive (able to identify all organisms regardless of prior characterization, including novel organisms) assay for eukaryotic symbiont assemblage characterization that is based on newly-designed PCR primers, a novel noise reduction strategy, and a user- friendly bioinformatic pipeline. Our goals in developing this assay were to 1) create an “industry standard” for symbiont community assessment, analogous to other standardized microbiome assays, 2) develop a broadly- applicable research method useful for all organisms and all sample types, 3) contribute to our understanding of the basic biology and ecology of human eukaryotic symbiont communities and 4) inform future development of “universal” diagnostic tools and targeted anti-parasitic therapeutics. We will optimize the assay in silico using custom databases, in vitro using a “mock community”, and ex vivo using samples from experimentally-infected animals. We will then validate the pipeline and assess its performance by analyzing human samples from two different populations in which intestinal parasites have previously been characterized by microscopy and PCR. Through completion of this project, we hope to provide a critically-needed research tool that will improve our understanding of human symbiont communities, and that, in turn, will inform advances in human health and medicine.

项目摘要/摘要 可归因于寄生虫的疾病在全球范围内造成大量的发病率和死亡率。然而，有越来越多的人 人类和共生体(这里定义为所有依赖宿主的真核生物)之间的关系的证据 生物体，包括寄生虫和共生体)并不总是有害的，事实上，有时可能会 重要的健康优势。共生菌组合可能有助于消化，赋予保护性免疫力，或者， 矛盾的是，提供了防止病原性寄生虫感染和疾病的保护。我们目前了解到 引起人类疾病的真核寄生虫的生物学和生态学，但我们对整个 原生动物和蠕虫群落的结构和功能，它们也是人类的殖民地。这 与细菌学和真菌学领域相比，缺点阻碍了寄生虫学领域的进步， 通过对细菌和真菌的研究，彻底改变了我们对人类健康的理解 微生物区系。事实上，大多数目前的寄生虫学方法都是为不同的目的而设计的：靶向 特定的、致病的生物。尽管用于无偏社区分析的方法已经得到验证和 原核生物和真菌的标准化，目前没有这样的方法用于真核共生体，包括 寄生虫。在没有标准化方法的情况下，对真核生物的有益影响的研究 共生菌群落及其在寄生虫病中的潜在作用代表着一个关键的知识鸿沟。 这项工作的最终目标是创建一个统一的、经过验证的研究工具，用于研究 人类共生体组合，可与细菌和真菌的研究成果相媲美 微生物群。为此，我们开发了一种新型的综合(能够识别所有生物体 不考虑先前的特征，包括新生物)真核共生体组合的分析 基于新设计的聚合酶链式反应引物、新的降噪策略和用户- 友好的生物信息学管道。我们开发这一检测方法的目标是：1)创建一种用于 共生菌群落评估，类似于其他标准化的微生物组分析，2)发展一种广泛的- 适用于所有生物体和所有样本类型的研究方法，3)有助于我们理解 人类真核共生群落的基本生物学和生态学，以及4)对未来发展的启示 “通用”诊断工具和有针对性的抗寄生虫疗法。我们将在电子计算机上优化检测方法 自定义数据库，在体外使用“模拟社区”，在体外使用实验感染的样本 动物。然后，我们将通过分析来自两个国家的人体样本来验证管道并评估其性能 肠道寄生虫以前通过显微镜和聚合酶链式反应确定的不同种群。 通过这个项目的完成，我们希望提供一个迫切需要的研究工具，以改善我们的 对人类共生群落的了解，这反过来将促进人类健康和 医药。