Elucidating impacts of genetic variability of Bifidobacterium strains on preterm infant gut immune responses

阐明双歧杆菌菌株遗传变异对早产儿肠道免疫反应的影响

• 批准号: 10283837
• 负责人: Steven Frese
• 金额: $ 7.28万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-30 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10283837
• 关键词: Address; Adopted; Affect; Bifidobacterium; Biological; Biological Assay; Cell Line; Cells; Clinical; Diet; Ecosystem; Enteral; Epithelial; Epithelial Cells; Gastrointestinal tract structure; Gene Cluster; Genes; Genetic; Genetic Transcription; Genotype; Growth; Health; Human Milk; Immune; Immune response; In Vitro; Infant; Infection; Inflammation; Inflammatory Response; International; Knowledge; Lactose; Link; Medical Societies; Metabolic; Modeling; Morbidity - disease rate; Necrotizing Enterocolitis; Neonatal; Neonatal Intensive Care Units; Oligosaccharides; Organism; Output; Patient-Focused Outcomes; Patients; Performance; Plant Roots; Play; Premature Infant; Probiotics; Recommendation; Research Personnel; Risk; Role; Safety; Structure; Testing; Therapeutic Intervention; Variant; Work; clinical care; experimental study; fitness; gastrointestinal epithelium; genomic variation; gut microbiome; immunoregulation; in vivo; infant gut microbiome; infant nutrition; interest; intestinal epithelium; lacto-N-neotetraose; microbiome composition; mortality; neonatal sepsis; patient population; response; symbiont; transcriptome sequencing; transcriptomics

Project Summary/Abstract The gastrointestinal tract of preterm infants plays a major role in overall infant nutrition, growth, and health. Increasing interest by clinicians and researchers has uncovered relationships between the gut microbiome and many of the primary causes of morbidity and mortality in preterm infants. To address these risks from the gut microbiome, probiotics are an attractive and translatable approach to remodel the infant gut microbiome. However, there is a strong need to understand the mechanism by which probiotic organisms act on the preterm gut and with the gut ecosystem in order to guide the rational selection of probiotic organisms for use in this patient population. In particular, there is a current lack of understanding as to how genomic variation among probiotic organisms may, or may not, influence their relative efficacy and/or safety in vivo. The proposed studies begin to address these issues by (1) examining the impact of genomic variations within a well characterized infant gut symbiont, and frequent probiotic organism, B. infantis, on ecological performance in in vitro competition models and then (2) how these variations affect the preterm gut epithelium in an epithelial cell line that closely mimics the cells found in the preterm infant gut. Together, these experiments seek to understand how diet (i.e. human milk), a probiotic gut symbiont (B. infantis), and the preterm host interact in terms of both transcriptional responses and host immune, proliferative, and necroptotic responses.

项目总结/摘要 早产儿的胃肠道在婴儿的整体营养、生长和健康中起着重要作用。 临床医生和研究人员的兴趣越来越大，已经发现了肠道微生物组与 许多早产儿发病和死亡的主要原因。从肠道着手解决这些风险 益生菌是重塑婴儿肠道微生物组的有吸引力和可转化的方法。 然而，强烈需要了解益生菌生物体作用于微生物的机制。 早产儿肠道和肠道生态系统，以指导合理选择益生菌生物体用于 这个病人群体。特别是，目前缺乏对基因组变异如何 可能影响或可能不影响它们在体内的相对功效和/或安全性。的 所提出的研究开始通过（1）检查井内基因组变异的影响来解决这些问题 特征为婴儿肠道共生体和常见的益生菌生物，B.的生态表现， 体外竞争模型，然后（2）这些变化如何影响上皮细胞中的早产肠上皮 这条线与早产儿肠道中发现的细胞非常相似。总之，这些实验旨在 理解饮食（即人乳）、益生菌肠道共生体（B.和早产儿宿主相互作用， 转录反应和宿主免疫、增殖和坏死性反应。