Acquisition of the Human Oral Microbiome

描述(由申请人提供)：人类微生物组项目揭示了物种水平上的成人人类微生物群落的组成，但它们是如何获得的以及它们的稳定性还不是很清楚。群落测序研究表明，在多个身体部位，类群的相对水平会随着时间的推移而波动，但在肠道和尿路中，人类微生物群落的成员在长期内表现出相当的稳定性。这表明，人类微生物组是一种稳定的特征，与人类基因组类似，对疾病和健康具有影响。这一口腔健康的重要潜在决定因素需要从口腔微生物区系的初始获取开始进行调查。我们最近在人类婴儿身上展示了一组共同的核心物种的强大组装，可以抵抗一些环境扰动的破坏。这一显著的特异性表明了一个令人惊讶的强大的过程，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有人类的遗传基础。我们假设每个人都有一组菌株/物种，这些菌株/物种特别适合他或她特定的基因决定的环境，并且这些细菌比那些没有血缘关系的人拥有的细菌更适合遗传后代。 如果是这样的话，人类微生物群可能是另一种形式的可遗传遗传物质，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获得口腔微生物组的自然历史，并测量两年内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母婴和收养母子二元来确定遗传对细菌从母亲传播到婴儿的贡献。我们将使用16S rRNA基因的454焦磷酸测序来确定细菌种类的相对水平。对菌株的全面分析在技术上才刚刚变得可行，这将使我们能够在新的分辨率水平上阐明稳定性、口腔微生物的组装和传播。我们将通过元基因组测序、将细菌序列映射到参考基因组以及确定单核苷酸多态(SNPs)来确定菌株的变异。拟议的研究将阐明从出生到青春期的口腔微生物群落的组装。它们将揭示微生物群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，它们随着时间的推移和对扰动的反应的稳定性，以及在多大程度上 人类口腔微生物群是一种可遗传的特征，类似于我们人类的基因组。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、风险评估以及益生菌/益生菌治疗战略的可行性。

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.