Acquisition of the Human Oral Microbiome

描述（由申请人提供）：人类微生物组计划揭示了物种水平上成人微生物群落的组成，但它们是如何获得的以及它们的稳定性如何尚不清楚。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，但在肠道和泌尿道，人类微生物群落的成员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类似于我们的人类基因组。这一重要的潜在口腔健康决定因素需要从口腔微生物群的初始获取开始进行调查。我们最近展示了人类婴儿中一组共同核心物种的强大组合，该组合可以抵抗许多环境扰动的破坏。这种显著的特异性表明了一个令人惊讶的强大过程，并提出了获得口腔微生物组的生物学蓝图，并且一些潜在的驱动因素具有人类遗传基础。我们假设，每个人体内都有一组菌株/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，这些细菌比那些不相关的个体更适合遗传后代。

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.