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: 10453313
• 负责人: Tony L. Goldberg
• 金额: $ 23.33万
• 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 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10453313
• 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; Gold; 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; Sensitivity and Specificity; Standardization; Structure; Taxonomy; The science of Mycology; Therapeutic; Tissues; Virus; Work; analysis pipeline; bacterial community; bacteriome; base; bioinformatics pipeline; design; 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.

项目总结/文摘