Probiotic Outcomes in Enteric Microflora (POEM) Study

描述(由申请人提供)：我们提出肠道微生物研究中的益生菌结果(POEM)研究，这是对先前从婴儿益生菌补充剂(TIPS)预防哮喘标志物试验(HL080074)收集的样本进行的二次数据分析。TIPS旨在检测婴儿每日补充干酪乳杆菌6个月对哮喘早期标志物发展到3岁的影响；采用双盲、安慰剂对照研究设计，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16S rRNA基因芯片微阵列方法，这是一种独立于培养的大规模并行方法，用于同时半定量检测细菌。对先前从TIPS队列(n=60)收集的粪便样本使用PhyloChip微阵列为表征益生菌补充剂如何改变肠道细菌群落提供了机会。POEM先导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，以确定每日补充益生菌对胃肠道细菌群落的影响。我们将评估(1)补充乳杆菌对新生儿肠道细菌群落的即时影响和(2)在补充6个月后对新生儿肠道细菌群落的长期影响，(3)细菌群落组成对哮喘早期标志物的影响。我们假设补充乳酸菌将在生命的第一年改变肠道定植的模式。从两组婴儿(出生时、1、3、6、9和12个月龄)采集粪便样本。我们将使用一种新的16S rRNA微阵列方法来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特定分类群的存在或不存在)以及细菌群落动态(细菌群落发展的纵向差异)。在这个队列中，我们使用每月随访来评估潜在的混杂因素，如接触母乳喂养、抗生素、日托、兄弟姐妹、宠物和国外旅行。我们有基于药片计数和大便分析的依从性数据。我们将使用多元回归方法来检验对照组和干预组在乳杆菌定植程度、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疾病的发展。这些数据将为我们提供补充乳杆菌后细菌群落变化的总体幅度和速度的估计，以及不同细菌群落组成的哪些指标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的益生菌结果(POEM)研究，这是一项先导性研究，旨在帮助我们了解新生儿补充益生菌如何影响定植于他们肠道的细菌，以及细菌种群的这种变化如何影响开发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，从研究中的婴儿粪便样本中鉴定细菌。POEM试点研究的数据将帮助我们找到潜在的方法，通过婴儿饮食补充来预防哮喘的早期迹象。

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.