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.

抽象的 细菌在人类肠道微生物组中提供重要的功能（例如代谢能力）； 然而，古细菌和微真核生物（真菌和原生动物）发挥的重要影响才刚刚开始 这些多微生物相互作用有助于调节机会主义的扩张和过度生长。 例如，生物体在形成免疫反应中发挥着重要作用。 在出生时或从环境中垂直获得，并在塑造身体的组成方面发挥重要作用 细菌群落的形成方式尚未完全了解。 早产儿出生时免疫系统非常不成熟，特别容易受到侵入性的侵害 感染，因此通常使用广谱抗生素和抗真菌药物治疗这些早产儿。 在新生儿重症监护室度过的时间最多，并经历各种压力源。 使用广谱抗菌药物可能对细菌发育和真菌产生长期影响 定植于婴儿肠道的群落，这反过来可能会影响长期健康。 肠道微生物群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 （例如，多组学）捕获影响功能相互作用的基因产物和特征代谢物 我们已经表明，E/VLBW 婴儿的早产可能存在明显的生态失调。 影响可能影响营养感应和/或卡路里处理能力的关键代谢特征， 这项研究将利用储存的临时粪便样本。 E/VLBW 婴儿，其中许多被跟踪至 4 岁，通过以下方式评估功能代谢网络 宏基因组测序和代谢组学的早期变化也可能有助于或 容易导致以后的健康，例如代谢功能障碍和肥胖。 E/VLBW 婴儿肠道微生物群受到干扰与长期健康后果有关，但尚未完全了解 已被理解，但可能包括对营养感知、热量摄入代谢过程的影响，以及 生命最初几年的后续生长。