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

项目摘要/摘要 早产儿的胃肠道在整个婴儿的营养、生长和健康中起着重要作用。 越来越多的临床医生和研究人员的兴趣已经揭示了肠道微生物群和 导致早产儿发病和死亡的许多主要原因。要从肠子里解决这些风险 微生物组、益生菌是一种有吸引力和可翻译的方法来重塑婴儿肠道微生物组。 然而，迫切需要了解益生菌对细菌的作用机制。 以指导合理选择用于早产肠道和肠道生态系统的益生菌 这群病人。特别是，目前对基因组变异是如何产生的缺乏了解 益生菌之间的相互作用可能会或可能不会影响它们在体内的相对有效性和/或安全性。这个 拟议的研究通过以下方式开始解决这些问题：(1)检查井内基因组变异的影响 婴幼儿肠道共生菌和常见益生菌婴儿芽孢杆菌对婴幼儿生长发育的影响 体外竞争模型以及(2)这些变异如何影响上皮细胞中的早产肠上皮 与早产儿肠道中发现的细胞非常相似的线条。总而言之，这些实验试图 了解饮食(即人奶)、益生菌肠道共生菌(婴儿乳杆菌)和早产宿主如何相互作用。 转录反应和宿主免疫、增殖和坏死反应的术语。

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.