Functional consequences of bacterial-fungal dysbiosis in E/VLBW infants

E/VLBW 婴儿细菌-真菌失调的功能后果

基本信息

批准号：
10373520
负责人：
Larry Joe Dishaw
金额：
$ 7.48万
依托单位：
UNIVERSITY OF SOUTH FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-02-09 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10373520
关键词：
4 year old Actinobacteria class Affect Age Antibiotics Antifungal Agents Archaea Bacteria Bacteroidetes Biochemical Pathway Birth Birth Weight Calories Categories Child Classification Communities Complex Data Development Diet Endotoxins Energy Intake Enterobacteriaceae Environment Environmental Exposure Equation Feeding behaviors Firmicutes Fluconazole Food Funding Gammaproteobacteria Growth Growth and Development function Health Hospitals Human Microbiome Human Milk Immune Immune response Immune system Infant Infection Inflammation Knowledge Life Link Lymphoid Tissue Measures Mediating Metabolic Metabolic dysfunction Metagenomics Microbe Mothers Neonatal Intensive Care Units Nutrient Obesity Organism Parents Pathway interactions Pattern Physiological Physiology Premature Birth Premature Infant Production Pseudomonas Ribosomal RNA Role Sampling Shapes Solid Stress Systemic infection Taxonomy Time Very Low Birth Weight Infant Virus Yeasts aged antimicrobial bacterial community base cohort detection of nutrient dysbiosis experience fungus gene product genetic signature gut bacteria gut colonization gut microbiome infant gut microbiome metabolomics metagenomic sequencing microbial community microbiome microbiome components microbiome research microbiome signature microorganism interaction multiple omics mycobiome nutrient metabolism opportunistic pathogen premature prevent prophylactic stool sample stressor

4 year old Actinobacteria class Affect Age Antibiotics Antifungal Agents Archaea Bacteria Bacteroidetes Biochemical Pathway Birth Birth Weight Calories Categories Child Classification Communities Complex Data Development Diet Endotoxins Energy Intake Enterobacteriaceae Environment Environmental Exposure Equation Feeding behaviors Firmicutes Fluconazole Food Funding Gammaproteobacteria Growth Growth and Development function Health Hospitals Human Microbiome Human Milk Immune Immune response Immune system Infant Infection Inflammation Knowledge Life Link Lymphoid Tissue Measures Mediating Metabolic Metabolic dysfunction Metagenomics Microbe Mothers Neonatal Intensive Care Units Nutrient Obesity Organism Parents Pathway interactions Pattern Physiological Physiology Premature Birth Premature Infant Production Pseudomonas Ribosomal RNA Role Sampling Shapes Solid Stress Systemic infection Taxonomy Time Very Low Birth Weight Infant Virus Yeasts aged antimicrobial bacterial community base cohort detection of nutrient dysbiosis experience fungus gene product genetic signature gut bacteria gut colonization gut microbiome infant gut microbiome metabolomics metagenomic sequencing microbial community microbiome microbiome components microbiome research microbiome signature microorganism interaction multiple omics mycobiome nutrient metabolism opportunistic pathogen premature prevent prophylactic stool sample stressor

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项目摘要

Abstract Bacteria deliver a significant functionality (e.g., metabolic capability) in the gut microbiome of humans; however, Archaea and microeukaryotes (fungi and protozoans) exert important influences that are only starting to be explored. These polymicrobial interactions help regulate the expansion and overgrowth of opportunistic organisms, and serve important roles in shaping immune responses. Fungal communities, for example, can be acquired vertically during birth or from the environment and serve important roles in shaping the composition of bacterial communities in ways that are not yet fully understood. Extremely and very low birth weight (E/VLBW) preterm infants are born with very immature immune systems and are particularly vulnerable to invasive infections, so they are often treated with broad-spectrum antibiotics and antifungals. These premature infants spend the most amount of time in the neonatal intensive care units and experience a variety of stressors. The use of broad-spectrum antimicrobials likely has long-term impacts on the developing bacterial and fungal communities that colonize the infant gut, and this in turn may impact long-term health. And because the metabolic potential of the gut microbiome is a product of the interactions of prokaryotic and eukaryotic microbes, there is an urgent need for ‘microbiome’ studies to incorporate more comprehensive approaches (e.g., multi-omic) to capture the gene products and signature metabolites impacting functional interaction networks. We have shown that prematurity among E/VLBW infants includes a significant dysbiosis that likely impacts key metabolite signatures that may influence nutrient sensing and/or calorie processing capabilities, in ways that can impact growth and development. This study will leverage banked temporal stool samples from E/VLBW infants, many of which were followed until the age of 4, to evaluate functional metabolic networks via metagenomic sequencing and metabolomics. Early changes to the microbiome may also contribute to or predispose later health, such as metabolic dysfunction and obesity. We propose that the products of a perturbed E/VLBW infant gut microbiome are linked to long-term health consequences that are not yet fully understood, but likely include effects on nutrient sensing, metabolic processing of caloric intake, and subsequent growth in the first few years of life.

抽象的细菌在人类的肠道微生物组中具有重要的功能（例如代谢能力）。但是，古细菌和微核（真菌和原生动物）发挥着重要的影响，仅启动要探索。这些多数型相互作用有助于调节机会主义的扩张和过度生长生物体，并在塑造免疫反应中起重要作用。例如，真菌社区可以是在出生期间或从环境中垂直获取，并在塑造组成中起重要作用细菌群落以尚未完全理解的方式。极其低的出生体重（E/VLBW）早产婴儿天生具有非常不成熟的免疫系统，特别容易受到侵入性感染，因此通常会用广谱抗生素和抗真菌剂进行治疗。这些过早的婴儿花费大量时间在新生儿重症监护病房中，并经历各种压力源。宽光谱抗菌剂的使用可能会对发育中的细菌和真菌产生长期影响殖民婴儿肠道的社区又可能影响长期健康。而且因为肠道微生物组的代谢潜力是原核生物和真核的相互作用的产物微生物，迫切需要“微生物组”研究以结合更全面的方法（例如，多球）捕获影响功能相互作用的基因产物和特征代谢产物网络。我们已经表明，E/VLBW婴儿的早产性包括明显的营养不良，可能影响可能影响营养敏感性和/或卡路里加工功能的关键代谢物特征影响增长和发展的方式。这项研究将利用从 E/VLBW婴儿，其中许多遵循直到4岁，以评估功能代谢网络通过元基因组测序和代谢组学。微生物组的早期更改也可能有助于或后来的健康，例如代谢功能障碍和肥胖症。我们建议扰动的E/VLBW婴儿肠道微生物组与尚未完全完全的健康后果有关理解齿，但可能包括对营养感应的影响，热量摄入的代谢处理以及随后在生命的头几年增长。