Probiotic Outcomes in Enteric Microflora (POEM) Study

描述（由申请方提供）：我们提出了益生菌对肠道微生物群（POEM）的影响研究，这是对先前从婴儿益生菌补充试验（TIPS）研究中收集的样本进行的二次数据分析，以预防哮喘标志物（HL 080074）。TIPS旨在检查婴儿每天补充干酪乳杆菌6个月对3岁以下哮喘早期标志物发展的影响;使用双盲，安慰剂对照研究设计，共有278名婴儿。在拟议的POEM研究中，我们将应用一种新的和新颖的16 S rRNA PhyloChip微阵列方法，这是一种不依赖于培养的大规模平行方法，用于同时半定量检测细菌。在先前从TIPS队列（n=60）收集的粪便样品的样品上使用PhyloChip微阵列提供了表征益生菌补充剂如何改变肠道细菌群落的机会。POEM试点研究的总体目标是应用最先进的科学技术来开发初步数据，以确定每日益生菌补充剂对胃肠道细菌群落的影响。我们将（1）评估乳杆菌补充剂对新生儿肠道细菌群落的即时影响和（2）在补充6个月期间和之后的长期影响，以及（3）将细菌群落组成对哮喘早期标志物的发展的影响相关联。我们假设，乳酸菌补充剂将改变整个生命的第一年肠道定植的模式。从两组动物中采集粪便样本（出生时、1、3、6、9和12月龄时）。我们将使用一种新的16 S rRNA PhyloChip微阵列方法评估新生儿肠道细菌群落组成，该方法将评估乳杆菌定植、细菌群落结构（根据微阵列荧光强度推断是否存在特定分类群）以及细菌群落动态（细菌群落发育的纵向差异）。在这个队列中，我们使用每月随访来评估潜在的混杂因素，如母乳喂养，抗生素，日托，兄弟姐妹，宠物和国外旅行。我们有基于药丸计数和粪便分析的依从性数据。我们将使用多元回归方法来测试对照组和干预组之间在乳酸菌定植程度、总细菌群落结构和细菌群落时间动态模式方面的差异。基于这种二次分析的结果，我们将进一步了解肠道细菌群落的变化如何影响特应性的发展。这些数据将为我们提供乳酸菌补充剂的细菌群落变化的总体幅度和速率的估计，以及细菌群落组成的不同测量与哮喘早期标志物的变化最相关。 公共卫生相关性：我们提出了肠道微生物群益生菌结果（POEM）研究，这是一项试点研究，旨在帮助我们了解新生儿益生菌补充剂如何影响肠道细菌，以及细菌种群的这种变化如何影响哮喘早期标志物的可能性。我们将使用一种新的尖端技术，PhyloChip，来识别研究中婴儿粪便样本中的细菌。POEM试点研究的数据将帮助我们找到通过婴儿膳食补充剂预防哮喘早期症状的方法。

DESCRIPTION (provided by applicant): We propose the Probiotic Outcomes on Enteric Microbiotia (POEM) Study, which is a secondary data analysis of previously collected samples from the Trial of Infant Probiotic Supplementation (TIPS) Study to Prevent Markers of Asthma (HL080074). TIPS was designed to examine the effects of daily Lactobacillus casei supplementation in infants for 6 months on the development of early markers of asthma to age three; using a double-blind, placebo controlled study design with 278 infants. In the proposed POEM Study, we will apply a new and novel 16S rRNA PhyloChip microarray approach that is a culture-independent, massively parallel method for simultaneous semi-quantitative detection of bacteria. Use of a PhyloChip microarray on a sample of previously collected stool samples from the TIPS cohort (n=60) presents an opportunity for characterizing how probiotic supplementation altered the intestinal bacterial community. The overall goal of the POEM pilot study is apply a state-of-the-science technology to develop preliminary data to determine the impact of daily probiotic supplementation on the gastrointestinal bacterial community. We will (1) assess the immediate effect and (2) prolonged effect of Lactobacillus supplementation on neonatal intestinal bacterial community during and after a six-month period of supplementation and (3) correlate the effects of the bacterial community composition on the development of early markers of asthma. We hypothesize that Lactobacillus supplementation will change the pattern of intestinal colonization throughout the first year of life. Stool samples have been collected from both groups (at birth, 1, 3, 6, 9 and 12 months of age). We will assess neonatal gut bacterial community composition using a novel 16S rRNA PhyloChip microarray approach, which will assess Lactobacillus colonization, bacterial community structure (presence or absence of specific taxa as inferred from microarray fluorescence intensity), as well as bacterial community dynamics (longitudinal differences in bacterial community development). In this cohort, we have used monthly follow-up to assess potential confounding factors such as exposure to breastfeeding, antibiotics, daycare, siblings, pets and foreign travel. We have data on adherence based on pill counts and stool analyses. We will use multivariate regression methods to test for differences between the control and intervention groups in the extent of Lactobacillus colonization, total bacteria community structure and bacterial community temporal dynamic patterns. Based on the results of this secondary analysis, we will further understand how changes in gut bacterial community may affect the development of atopy. This data will give us an estimate of the overall magnitude and rate of changes in bacterial communities with Lactobacillus supplementation, as well as which of different measures of bacterial community composition are most associated with changes in early markers of asthma. PUBLIC HEALTH RELEVANCE: We propose the Probiotic Outcomes on Enteric Microbiotia (POEM) Study, which is a pilot study to help us understand how probiotic supplementation of newborn babies affects the bacteria that colonize their gut, and how such changes in the bacterial population affect the likelihood of developing early markers of asthma. We will use a new cutting-edge technology, the PhyloChip, to identify bacteria from stool samples of the infants in the study. Data from the POEM pilot study will help us find ways of potentially preventing early signs of asthma through dietary supplementation of infants.