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

人类免疫缺陷病毒感染人群的口腔微生物组和龋齿

• 批准号: 10189549
• 负责人: MODUPE COKER
• 金额: $ 21.99万
• 依托单位: CLEMSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-11 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10189549
• 关键词: 16S ribosomal RNA sequencing; Acids; Affect; Bacteria; Child; Childhood; Clinical; Communities; Complex; DNA sequencing; Dental; Dental Plaque; Dental caries; Development; Disease; Down-Regulation; Ecology; Family; Funding; Gene Expression; Gene Expression Regulation; Genes; Genetic Polymorphism; HIV; HIV Infections; Health; Health Transition; Highly Active Antiretroviral Therapy; Homologous Gene; Human Microbiome; Immune response; Individual; Infection; Integration Host Factors; Intervention; Knowledge; Maintenance; Measures; Metabolic Pathway; Metagenomics; Microbial Taxonomy; Neisseria; Nigeria; Nucleotides; Oral cavity; Oral health; Outcome; Pathogenesis; Pathway interactions; Population; Prevalence; Prevention; Production; Public Health; Quality of life; Research; Resolution; Risk; Role; Saliva; Salivary; Sampling; Site; Streptococcus; System; Taxonomy; Tooth structure; Translating; Treatment Protocols; United States National Institutes of Health; Up-Regulation; Variant; cohort; evidence base; fungus; gut microbiome; improved; infancy; innovation; insight; metatranscriptomics; microbiome; microbiota; oral microbiome; pan-genome; pathogen; rRNA Genes; study population; synergism

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.

项目概要 儿童龋齿是一个严重的公共卫生问题，影响儿童的近期和长期生活质量 孩子及其家人。最近的研究表明，艾滋病毒感染儿童的龋齿患病率有所增加。 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量减少 流速，这可能使他们容易患龋齿。这些发现强化了基于证据的必要性 预防和治疗以促进和维护口腔健康。现在有充分的证据表明 人类微生物组与我们的健康密切相关，针对肠道微生物组的研究表明 显示了艾滋病毒+个体的不利社区转变，其中正常共生体被耗尽并且病原体 丰富了。 HIV感染对口腔微生物组影响的初步研究表明， 健康人和艾滋病病毒感染者唾液中某些细菌和真菌的分布是不同的。 随着牙齿从健康状态转变，牙菌斑群落的分类组成发生了巨大变化 疾病包括产生碱性化合物的潜在有益细菌减少和 高产酸和耐酸类群的增加。该项目的目标是提供详细的分类学 儿童龋病不同阶段牙菌斑群落及基因表达特征 暴露、感染和接受 HIV 治疗。为了实现这一目标，我们将利用独特的优势 尼日利亚感染艾滋病毒的儿童群体。在这里，我们将采取一种创新方法：(i) 结合 16S rRNA 基因具有两个额外的基因座，可为链球菌、奈瑟菌和 真菌，以及（ii）将详细的分类学分析纳入参考泛基因组的构建中 宏转录组学。在目标 1 中，针对接受 HAART 治疗的 HIV 感染儿童、暴露于 HIV 但未感染的儿童，以及 对于未暴露和未感染（HUU）的儿童，我们将利用宏基因组学（高通量扩增子 测序）来分析从代表六个牙齿的牙菌斑样本的分类组成 龋齿的进展阶段。在目标 2 中，使用从代表 6 个牙齿的牙齿中获取的牙菌斑样本 龋齿的进展阶段，从接受 HAART 且未暴露/未感染的 HIV 感染儿童中获得 孩子们，我们将利用宏转录组学来测量社区基因表达的变化，以确定 HIV 感染和治疗如何影响与龋齿相关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暴露、感染和治疗如何 影响儿童龋齿的生态和发展。最终，这些知识将转化为改进的 可能减轻艾滋病毒感染者患龋齿风险增加的预防和干预策略 被感染的孩子。