Acquisition of the Human Oral Microbiome

描述（由申请人提供）：人类微生物组项目已经揭示了成年人类微生物群落在物种水平上的组成，但它们是如何获得的以及它们的稳定性尚不清楚。群落测序研究表明，在多个身体部位，分类群的相对水平会随着时间的推移而波动，但在肠道和泌尿道中，人类微生物群落的成员资格在长期内表现出相当大的稳定性。这表明，人类微生物组是一个稳定的特征，对疾病和健康的影响与人类基因组相似。口腔健康的这一重要的潜在决定因素需要从最初获得口腔微生物群开始进行研究。我们最近已经证明了一个强大的组装的共同核心集的物种在人类婴儿，是耐破坏的一些环境扰动。这种显著的特异性表明了一个令人惊讶的强大过程，并表明了获得口腔微生物组的生物蓝图，一些潜在的驱动因素具有人类遗传基础。我们假设，每个人都有一组菌株/物种，特别适合他或她特定的遗传决定的环境，这些细菌比那些不相关的个体更适合遗传后代。 如果是这样的话，人类微生物组可能是另一种形式的遗传物质，从父母传给后代-另一种“表观遗传学”。在目标1中，我们将阐明从婴儿期到青春期口腔微生物组获得的自然历史，并测量两年多来微生物群落成员的稳定性。在目标2中，我们将通过比较生物学和收养的母子二人组来确定遗传学对细菌从母亲传播到婴儿的贡献。我们将使用16 S rRNA基因的454焦磷酸测序来确定细菌物种的相对水平。对菌株的全面分析在技术上刚刚变得可行，这将使我们能够在新的分辨率水平上阐明稳定性、口腔微生物组的组装和传播。我们将通过宏基因组测序和细菌序列与参考基因组的映射以及确定单核苷酸多态性（SNP）来确定菌株变异。拟议的研究将阐明从出生到青春期口腔微生物群落的组装。它们将揭示微生物组在物种和菌株水平上的复杂性，人类共享一组核心物种和菌株的程度，它们随时间的稳定性和对扰动的反应，以及在多大程度上 人类口腔微生物组是一种遗传特征，类似于我们的人类基因组。这些发现将对疾病和健康产生重大影响，包括疾病易感性的可能决定因素、风险评估和益生元/益生菌疗法策略的可行性。

DESCRIPTION (provided by applicant): The Human Microbiome Project has revealed the composition of adult human microbial communities at the level of species, but how they are acquired and how stable they are is not well understood. Community sequencing studies have shown relative levels of taxa to fluctuate over time at multiple body sites, but in the gut and urinary tract, membership of human microbial communities shows considerable stability over the long term. This suggests that the human microbiome is a stable feature with implications for disease and health similar to that of our human genome. This important potential determinant of oral health needs to be investigated starting with the initial acquisition of the oral microbiota. e have recently demonstrated a robust assembly of a common core set of species in human infants that is resistant to disruption by a number of environmental perturbations. This remarkable specificity demonstrates a surprisingly robust process and suggests a biologic blueprint for acquisition of the oral microbiome, and some potential drivers have a human genetic basis. We hypothesize that each human harbors a set of strains/species that is particularly well adapted to his or her specific genetically determined environment, and that these bacteria are a better fit for genetic offspring than those harbored by unrelated individuals. If so, the human microbiome may be another form of heritable genetic material passed from parent to offspring -- another sort of "epigenetics". In aim 1 we will elucidate the natural histor of acquisition of the oral microbiome from infancy to adolescence and measure stability of microbial community membership over two years. In aim 2 we will determine the contribution of genetics to bacterial transmission from mothers to babies by comparing biologic and adoptive mother-child dyads. We will determine relative levels of bacterial species using 454 pyrosequencing of the 16S rRNA gene. Comprehensive analysis of strains has just become technically feasible, and this will allow us to elucidate stability, assembly of the oral microbiom and transmission at a new level of resolution. We will determine strain variation by metagenomic sequencing and mapping of bacterial sequences to reference genomes and determining single nucleotide polymorphisms (SNPs). The proposed studies will elucidate the assembly of oral microbial communities from birth through adolescence. They will reveal the complexity of the microbiome at the level of species and strain, the extent to which humans share a core set of species and strains, their stability over time and in response to perturbations, and to what extent the human oral microbiome is a heritable feature, similar to our human genome. These findings will have major implications for disease and health including possible determinants of disease susceptibility, risk assessment and feasibility of strategies for prebiotic/probiotic therapies.