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: 10424444
• 负责人: MODUPE COKER
• 金额: $ 20.66万
• 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 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10424444
• 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.

项目摘要 儿童龋齿是一个严重的公共卫生问题，影响两者的直接和长期生活质量 孩子及其家人。最近的研究表明，在感染HIV的儿童中龋齿的患病率提高。 此外，高度活性抗逆转录病毒治疗（HAART）的HIV感染儿童显示唾液降低 流速，可能使它们偏爱龋齿。这些发现加强了基于证据的需求 预防和治疗口腔健康。现在有充分记录在 人类微生物组与我们的健康密切相关，而专注于肠道微生物组的研究 显示了艾滋病毒+个体的不良社区变化，在正常的儿童耗尽和病原体的情况下 丰富。 HIV感染对口腔微生物组的影响的初步研究表明 健康和艾滋病毒+个体之间某些细菌和真菌在唾液中的分布不同。 牙齿斑块群落显示出分类学组成的巨大转变，因为牙齿从健康中转变 疾病，包括产生碱性化合物的潜在有益细菌的降低和 高度酸性和酸性分类单元的增加。该项目的目的是提供详细的分类学 和儿童龋齿不同阶段牙齿斑块群落的基因表达表征 受HIV暴露，感染和治疗。为此，我们将利用独特的 尼日利亚感染艾滋病毒的儿童队列。在这里，我们将采取一种创新的方法，（i）结合了16s rRNA基因具有两个附加基因座，可为链球菌，奈瑟氏菌和链球菌提供水平分辨率 真菌和（ii）将详细的分类学分析纳入构建参考式基因组 metatranscriptomics。在AIM 1中，对于HAART的HIV感染儿童，HIV暴露但未感染的儿童，以及 未接触和未感染（HUU）儿童，我们将使用宏基因组学（高吞吐量扩增子 测序）介绍从牙齿获得的斑块样品的分类组成，代表六个 龋齿的渐进阶段。在AIM 2中，使用从代表六个的牙齿获得的斑块样品 龋齿的渐进阶段，从HAART上的艾滋病毒感染的儿童和未感染的儿童获得 我们将利用metatranscriptomics来衡量社区基因表达的变化以确定的儿童 龋齿中涉及的细菌和真菌代谢途径如何受HIV感染和治疗的影响。 我们预计这些目标将对艾滋病毒接触，感染和治疗方式产生第一个详细的见解 影响儿童龋齿的生态和发展。最终，这些知识将转化为改进 预防和干预策略可能会减轻艾滋病毒中龋齿的风险增加 感染的孩子。