Oral Microbiomes and Dental Caries in a Human Immunodeficiency Virus Infected Population

项目总结 儿童期龋病是一个严重的公共卫生问题，影响儿童和儿童的近期和长期生活质量 孩子和他的家人。最近的研究表明，感染艾滋病毒的儿童患龋率上升。 此外，接受高效抗逆转录病毒治疗(HAART)的艾滋病毒感染儿童表现出唾液减少 流速，这很可能使他们容易龋齿。这些发现加强了以证据为基础的必要性 促进和维护口腔健康的预防和治疗。现在有充分的证据表明， 人类微生物群与我们的健康密切相关，而专注于肠道微生物群的研究已经 对HIV+个体表现出不利的社区转移，其中正常共生体枯竭，病原体 富足了。有关艾滋病毒感染对口腔微生物群影响的初步研究表明， 某些种类的细菌和真菌在唾液中的分布在健康人和HIV+的人中是不同的。 随着牙齿从健康状态转变，牙菌斑群落的分类组成发生了戏剧性的变化 这种疾病包括产生基本化合物的潜在有益细菌的减少和 高度产酸和耐酸的类群增加。这个项目的目标是提供一个详细的分类学 儿童龋病不同阶段菌斑群落的基因表达特征 易受艾滋病毒感染和治疗的影响。为了实现这一点，我们将利用一个独特的 尼日利亚一群感染艾滋病毒的儿童。在这里，我们将采取一种创新的方法，即(I)结合16 RRNA基因，具有两个额外的基因座，为链球菌、奈瑟氏菌和链球菌提供物种水平的分辨率 真菌，以及(Ii)在构建参考泛基因组时纳入了详细的分类学概况 变态剪辑学。在目标1中，对于HAART中感染艾滋病毒的儿童，暴露于艾滋病毒但未感染的儿童，以及 未暴露和未感染(HUU)儿童，我们将利用元基因组学(高通量扩增) 测序)以描述从代表六个牙齿的牙齿获得的菌斑样本的分类组成 进展期的龋齿。在目标2中，使用从代表六个牙齿的牙菌斑样本 HAART和未暴露/未感染的HIV感染儿童获得的进展期龋齿 孩子们，我们将利用元转录组学来测量社区基因表达的变化，以确定 艾滋病毒感染和治疗如何影响参与龋齿的细菌和真菌代谢途径。 我们预计，这些目标将首次详细了解艾滋病毒的暴露、感染和治疗 影响儿童龋齿的生态和发育。最终，这些知识将转化为 预防和干预策略，有可能降低艾滋病毒患龋率增加的风险 被感染的孩子。

PROJECT SUMMARY Childhood caries is a serious public health problem affecting the immediate and long-term quality of life of both the child and its family. Recent studies have shown an increased prevalence of caries in HIV-infected children. Furthermore, HIV-infected children on highly active antiretroviral therapy (HAART) show decreased salivary flow rates, which likely predispose them to caries. These findings reinforce the need for evidence based prevention and treatment for the promotion and maintenance of oral health. It is now well documented that the human microbiome is intimately associated with our health, and studies focusing on the gut microbiome have shown adverse community shifts for HIV+ individuals, where normal commensals are depleted and pathogens enriched. Preliminary studies of the impact of HIV infection on the oral microbiome have shown that the distribution of certain species of bacteria and fungus in saliva is different between healthy and HIV+ individuals. Dental plaque communities show a dramatic shift in taxonomic composition as a tooth transitions from health to disease that includes a decrease in potentially beneficial bacteria that produce basic compounds and an increase in highly acidogenic and aciduric taxa. The objective of this project is to provide a detailed taxonomic and gene expression characterization of dental plaque communities at different stages of caries for children subject to HIV exposure, infection, and treatment. To accomplish this, we will take advantage of a unique cohort of HIV infected children in Nigeria. Here, we will take an innovative approach that (i) combines the 16S rRNA gene with two additional loci that provide species level resolution for the Streptococci, Neisseria, and fungi, and (ii) incorporates detailed taxonomic profiling in the construction of a reference pan-genome for metatranscriptomics. In Aim 1, for HIV-infected children on HAART, HIV exposed but uninfected children, and unexposed and uninfected (HUU) children, we will utilize metagenomics (high throughput amplicon sequencing) to profile the taxonomic composition of plaque samples obtained from teeth that represent six progressive stages of caries. In Aim 2, using plaque samples obtained from teeth that represent six progressive stages of caries, obtained from HIV-infected children on HAART and unexposed/uninfected children we will utilize metatranscriptomics to measure changes in community gene expression to determine how bacteria and fungal metabolic pathways involved in caries are influenced by HIV infection and treatment. We anticipate that these aims will yield the first detailed insight into how HIV exposure, infection, and treatment affect the ecology and development of caries in children. Ultimately, this knowledge will translate into improved prevention and intervention stratergies that could potentially mitigate an increased risk of caries in an HIV infected child.