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Bioinformatics analysis of host-microbiome interaction in oral cavity

口腔宿主-微生物组相互作用的生物信息学分析

基本信息

批准号：
10284591
负责人：
Janina P Lewis
金额：
$ 14.36万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10284591
关键词：
Affect Anaerobic Bacteria Antibiotic Resistance Antibiotic Therapy Antibiotics Award Bacteria Bacterial Infections Bioinformatics Chronic Disease Clinical Complex Consensus Data Data Analyses Dental Development Ensure Environment Forsythia Funding Fusobacterium nucleatum Genome Grant Growth Health Health Promotion Human Microbiome Immune response Incidence Infection Inflammation Inflammatory Inflammatory Response K-18 conjugate Macaca mulatta Mechanics Mentors Mentorship Metabolic Metagenomics Methods Metronidazole Modeling Monitor Oral Oral cavity Oral mucous membrane structure Organism Pathogenicity Pathway interactions Periodontal Diseases Periodontitis Porphyromonas gingivalis Prevention Prevention strategy Probability Pyruvate synthase Research Research Personnel Research Proposals Risk Factors Site Testing Therapeutic Tissues Tooth structure Training Treponema denticola antimicrobial base career commensal microbes craniofacial dysbiosis effectiveness evaluation efficacy testing gut microbiota host microbiome in vivo insight knock-down laboratory experience meetings metatranscriptomics microbial microbiome microbiome composition microbiome sequencing microorganism nonhuman primate novel novel therapeutics oral anaerobes oral microbiome pathogen pathogenic bacteria periodontopathogen subgingival microbiome targeted treatment therapeutic effectiveness transcriptome treatment strategy

项目摘要

This is a K18 application for a Short-term Mentored Career Enhancement Award in Dental, Oral and Craniofacial Research for Mid-Career and Senior Investigators that focuses on bioinformatics analysis of oral microbiome implicated in periodontitis. The training component is an extension of a research proposal funded by a different mechanism. Research: Periodontal diseases are inflammatory conditions of the tissues supporting teeth resulting from the inflammatory response of the host. However, in order to trigger the inflammatory conditions bacteria must be present. Not all bacteria trigger inflammatory response from the host and indeed, some bacteria are beneficial as they provide protective barrier against periodontal diseases. It is the pathogenic ones, such as the red complex bacteria, that when present in higher numbers, result in inflammatory response from the host. These bacteria include Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Fusobacterium nucleatum. Thus, we hypothesize that in order to reduce the incidence of periodontal diseases, targeted therapies aimed at reducing the growth of the pathogenic bacteria while sparing commensal microflora are needed. Mechanical antimicrobial therapies as well as adjunct antibiotics currently used to treat this chronic disease are broad spectrum, thus targeting both pathogenic and beneficial bacteria. Here we propose to use amixicile, a novel systemic therapeutic, that selectively target anaerobic bacteria such as the ones listed above. The antimicrobial will be used to specifically deplete the oral subgingival microbiome of anaerobic bacteria and then examine the effect of the microbiomes on host’s response to both treated and control (un-treated) microbiomes. Using such treatment we will test the ability of amixicile to alter the composition of the microbiome from a dysbiotic pro-inflammatory one to a health-associated microbiome. Training Plan and Environment. In this K18 training grant the PI will get training in understanding and using methods for highthroughput sequencing data analysis derived from sequencing the microbiomes at both genome and transcriptome levels as well as determination of the transcriptome of the host response. That data will then be integrated to get an insight into the host response depending on the composition of the microbiome. The training will be done under the mentorship of two experts in bioinformatics. Variety of activities is proposed including: laboratory experience, coursework, bioinformatics analysis and presentation at scientific meetings. Thus the proposal will pave a pathway to ensure that the PI will get thorough training in understanding of the bioinformatics approaches applied to study host-pathogen interaction in a very comprehensive manner.

这是一份K18牙科、口腔和颅面专业短期导师职业提升奖的申请表专注于口腔微生物组生物信息学分析的中高级研究人员研究与牙周炎有关。培训部分是由不同机构资助的研究方案的延伸机制。研究：牙周病是支持牙齿的组织的炎症状态，由宿主的炎症反应。然而，为了触发炎症条件，细菌必须现在时。并不是所有的细菌都会引发宿主的炎症反应，确实，有些细菌是有益的。因为它们提供了对牙周病的保护屏障。它是致病的，比如红色复杂的细菌，当数量较多时，会引起宿主的炎症反应。这些细菌包括牙龈卟啉单胞菌、连翘坦纳氏菌、齿密螺旋体和梭杆菌核糖体。因此，我们假设，为了降低牙周病的发病率，有针对性地旨在减少病原菌生长同时避免共生微生物群的治疗方法是需要的。目前用于治疗这一慢性疾病的机械抗菌疗法以及辅助抗生素疾病的范围很广，因此既针对致病细菌，也针对有益细菌。在这里，我们建议使用阿米西林，一种新的全身治疗药物，选择性地针对上面列出的厌氧细菌。这种抗菌剂将被用来专门耗尽口腔中厌氧细菌的微生物群和然后检查微生物群对宿主对处理和对照(未处理)的反应的影响微生物群。利用这样的处理，我们将测试阿米西林改变微生物组组成的能力。从益生菌、促炎微生物到与健康相关的微生物群。培训计划和环境。在这份K18培训补助金中，PI将接受理解和使用方面的培训从两个基因组上的微生物组测序得出的高通量测序数据分析方法和转录组水平以及测定寄主反应的转录组。然后，这些数据将整合在一起，根据微生物组的组成深入了解宿主的反应。这个培训将在两名生物信息学专家的指导下进行。建议活动的种类繁多包括：实验室经验、课程、生物信息学分析和在科学会议上的陈述。因此，这项建议将铺平一条道路，以确保私家侦探得到彻底的培训，了解生物信息学方法应用于以非常全面的方式研究宿主-病原体的相互作用。