Propagation and Characterization of Phage Related to Human Growth

与人类生长相关的噬菌体的繁殖和表征

基本信息

批准号：
10668108
负责人：
Lori R Holtz
金额：
$ 23.48万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-01-20 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10668108
关键词：
Affect Agar Age Animal Model Bacteria Bacterial Genome Bacteriolysis Bacteriophages Biology Cause of Death Cell Separation Cells Child Child Development Child Health Childhood Colorectal Cancer Communities Complex DNA amplification Data Diabetes Mellitus Diagnosis Disease Disease Marker Dyes Enteral Equilibrium Feces Fluorescence-Activated Cell Sorting Functional disorder Future Genome Genomics Growth Health Human Human body Hypertension Immune response Impairment Individual Inflammatory Inflammatory Bowel Diseases Intervention Knowledge Label Link Longitudinal cohort Lytic Mechanics Methods Molds Necrotizing Enterocolitis Nucleic Acids Population Preschool Child Prevention Process Prokaryotic Cells Publishing Reagent Rural Sampling Structure Techniques Viral Virus bacterial community bacteriome deep sequencing dysbiosis experimental study fitness genetic signature global health gut health gut microbiome in silico interest low and middle-income countries microbial microbial signature mortality novel novel strategies optical spectra prevent screening stool sample virome virus culture

Affect Agar Age Animal Model Bacteria Bacterial Genome Bacteriolysis Bacteriophages Biology Cause of Death Cell Separation Cells Child Child Development Child Health Childhood Colorectal Cancer Communities Complex DNA amplification Data Diabetes Mellitus Diagnosis Disease Disease Marker Dyes Enteral Equilibrium Feces Fluorescence-Activated Cell Sorting Functional disorder Future Genome Genomics Growth Health Human Human body Hypertension Immune response Impairment Individual Inflammatory Inflammatory Bowel Diseases Intervention Knowledge Label Link Longitudinal cohort Lytic Mechanics Methods Molds Necrotizing Enterocolitis Nucleic Acids Population Preschool Child Prevention Process Prokaryotic Cells Publishing Reagent Rural Sampling Structure Techniques Viral Virus bacterial community bacteriome deep sequencing dysbiosis experimental study fitness genetic signature global health gut health gut microbiome in silico interest low and middle-income countries microbial microbial signature mortality novel novel strategies optical spectra prevent screening stool sample virome virus culture

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项目摘要

Project Description Bacteriophage (phage) are viruses that infect prokaryotes. Bacteriophage can destroy the bacterial cell they infect (bacteriolysis), and thereby mold bacterial populations. Our incomplete knowledge of phage biology, in particular phage-bacterial pairing, the range of bacterial hosts for a given phage, and the effect of an introduced phage on phage-bacteria community dynamics limits our ability to understand how phage impact gut health. The human gut contains a highly complex community of bacteria and phage. Alterations in bacteriophage communities are associated with disorders such as inflammatory bowel disease, diabetes, hypertension, and colorectal cancer. Stunting (poor linear growth) adversely affects one-third of the half-billion preschool children in low and middle-income countries and is associated with ~20% of all-cause deaths before age five. Stunting is believed to be a consequence of environmental enteric dysfunction (EED). We recently defined the comprehensive gut virome and the bacterial gut microbiome in a longitudinal cohort of rural Malawian children with EED. We found 13 bacteriophage that were differentially associated with linear growth. Twelve of the 13 bacteriophage were associated with subsequent poor growth velocity. Intriguingly, we found an inverse relationship between bacteria and bacteriophage richness in children with subsequent poor linear growth (bacteriophage richness diminishes as bacterial richness increases in children with poor growth). Our data suggest that disruption of the equilibrium between bacteria and bacteriophage communities might impair childhood linear growth. This observation that changes in the phage community are associated with subsequent linear growth is intriguing as there is currently no way to treat or prevent EED and stunting. Additionally, the pathophysiology underlying EED is not well understood, and there currently is not a reliable marker of disease. Therefore, further understanding of these bacteriophage as either drivers or markers of disease would be a significant advance for the field. We suggest that further characterization, and potentially future manipulation, of these microbial signatures may reveal novel avenues for prevention, diagnosis, or treatment of EED and stunting. Here we aim to advance understanding of phage biology, global gut health, and child health and development. We will identify and grow bacterial host(s) of the phages of interest, culture phages, and further characterize them. While we propose to apply our methods to study phage in the context of EED, execution of this approach will also provide a much-needed roadmap for future studies of phage in other disorders.

项目描述噬菌体（噬菌体）是感染原核的病毒。噬菌体会破坏细菌细胞它们感染（细菌溶解），从而塑造细菌种群。我们对噬菌体的不完整知识生物学，特别是噬菌体 - 细菌配对，给定噬菌体的细菌宿主范围，以及引入噬菌体 - 细菌社区动态的噬菌体限制了我们了解噬菌体影响的能力肠道健康。人类肠道包含一个高度复杂的细菌和噬菌体社区。改变噬菌体群落与炎症性肠病，糖尿病，高血压和结直肠癌。发育迟缓（线性增长差）对低和中等收入国家与五岁之前的全因死亡人数约20％有关。相信发育迟缓是环境肠功能障碍（EED）的结果。我们最近定义了全面的肠道在马拉维农村儿童的EED纵向队列中，病毒素和细菌肠道微生物组。我们发现13个与线性生长不同相关的噬菌体。 13个中的十二个噬菌体与随后的生长速度差有关。有趣的是，我们发现了一个逆细菌与随后线性生长差的儿童的细菌与噬菌体丰富度之间的关系（随着生长不良的儿童的细菌丰富度的增加，噬菌体丰富度会降低）。我们的数据表明细菌与噬菌体社区之间平衡的破坏可能会损害童年线性生长。这种观察到噬菌体社区的变化与随后的线性增长有关的观察是有趣的是，目前没有办法治疗或防止EED和发育迟缓。另外，病理生理学潜在的EED尚不清楚，目前没有可靠的疾病标记。所以，进一步了解这些噬菌体是疾病的驱动因素或标志物将是重要的前进。我们建议对这些进一步的表征以及可能的未来操纵微生物特征可能揭示了预防，诊断或治疗EED和发育迟缓的新途径。在这里，我们旨在提高人们对噬菌体生物学，全球肠道健康以及儿童健康与发展的了解。我们将识别和成长感兴趣的噬菌体，培养噬菌体的细菌宿主，并进一步表征他们。当我们建议在EED的背景下应用我们的方法研究噬菌体时，执行此操作方法还将为未来的其他疾病噬菌体研究提供急需的路线图。