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

项目摘要 儿童龋病是一个严重的公共卫生问题，影响儿童的近期和远期生活质量 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齿的患病率增加。 此外，接受高效抗逆转录病毒治疗（HAART）的艾滋病毒感染儿童的唾液分泌减少， 流率，这可能使他们容易患龋齿。这些发现加强了基于证据的必要性 预防和治疗，以促进和维持口腔健康。现在有充分的证据表明， 人体微生物组与我们的健康密切相关，专注于肠道微生物组的研究已经 显示出对艾滋病毒阳性个体不利的社区变化，其中正常的免疫系统被耗尽， 丰富了HIV感染对口腔微生物组影响的初步研究表明， 唾液中某些种类的细菌和真菌的分布在健康个体和HIV阳性个体之间是不同的。 牙菌斑社区显示出从健康牙齿过渡到分类组成的戏剧性转变 疾病，包括减少潜在的有益细菌，产生碱性化合物和 高产酸和耐酸类群增加。本项目的目的是提供一个详细的分类 儿童龋病不同阶段菌斑群落的基因表达特征 艾滋病毒暴露、感染和治疗。为了实现这一目标，我们将利用一个独特的 尼日利亚艾滋病毒感染儿童队列。在这里，我们将采取一种创新的方法，（i）结合16 S rRNA基因和两个额外的基因座，为链球菌、奈瑟氏球菌和 真菌，和（ii）在构建参考泛基因组时纳入详细的分类学分析， 元转录组学在目标1中，对于接受高效抗逆转录病毒治疗的艾滋病毒感染儿童，暴露于艾滋病毒但未感染的儿童， 未暴露和未感染（HUU）的儿童，我们将利用宏基因组学（高通量扩增子 测序）来分析从代表六种牙菌斑的牙齿获得的牙菌斑样品的分类组成， 龋齿的进展阶段。在目标2中，使用从代表六个牙齿的牙齿中获得的牙菌斑样本， 从接受HAART治疗的HIV感染儿童和未暴露/未感染的儿童中获得的龋齿进行性阶段 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 细菌和真菌的代谢途径如何参与龋齿受艾滋病毒感染和治疗的影响。 我们预计，这些目标将产生第一个详细的洞察艾滋病毒暴露，感染和治疗， 影响儿童龋齿的生态和发育。最终，这些知识将转化为改进的 预防和干预策略，可以潜在地减轻增加的风险龋齿在艾滋病毒 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.