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

• 批准号: 10569645
• 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
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-09 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10569645
• 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; Eukaryota; Extremely Low Birth Weight Infant; 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; Protozoa; Pseudomonas; Ribosomal RNA; Role; Sampling; Shapes; Solid; Stress; Systemic infection; Taxonomy; Time; Very Low Birth Weight Infant; Virus; Yeasts; aged; antimicrobial; bacterial community; 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; success

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.

摘要 细菌提供重要的功能（例如，代谢能力）; 然而，微生物和微真核生物（真菌和原生动物）的重要影响才刚刚开始 有待探索这些多微生物的相互作用有助于调节机会性微生物的扩张和过度生长。 生物体，并在形成免疫反应中发挥重要作用。例如，真菌群落可以 在出生时或从环境中垂直获得，并在塑造 细菌群落的方式尚未完全了解。极低和极低出生体重儿（E/VLBW） 早产儿出生时具有非常不成熟的免疫系统， 感染，所以他们经常用广谱抗生素和抗真菌药治疗。这些早产儿 在新生儿重症监护室度过的时间最多，并经历了各种压力。的 广谱抗菌剂的使用可能会对细菌和真菌的生长产生长期影响。 这可能会影响到婴儿肠道中的细菌群落，而这反过来又可能影响长期健康。并且因为 肠道微生物组的代谢潜力是原核生物和真核生物相互作用的产物。 微生物，迫切需要“微生物组”研究纳入更全面的方法 (e.g.,多组学）以捕获影响功能相互作用的基因产物和特征代谢物 网络.我们已经表明，E/VLBW婴儿中的早产包括一种明显的生态失调， 影响可能影响营养感测和/或卡路里处理能力的关键代谢物特征， 可以影响增长和发展的方式。本研究将利用来自以下地区的库存颞部粪便样本： E/VLBW婴儿，其中许多被跟踪到4岁，以评估功能代谢网络， 宏基因组测序和代谢组学。微生物组的早期变化也可能有助于或 易导致日后的健康，例如代谢功能障碍和肥胖。我们建议，产品的一个 受干扰的E/VLBW婴儿肠道微生物组与长期健康后果有关， 理解，但可能包括对营养感测，热量摄入的代谢过程， 在生命的最初几年里，