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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K18申请牙科，口腔和颅面短期指导职业提升奖针对职业中期和高级研究人员的研究，重点是口腔微生物组的生物信息学分析与牙周炎有关培训部分是一项研究提案的延伸，机制研究：牙周病是由牙周炎引起的支持牙齿的组织的炎症状态。宿主的炎症反应。然而，为了触发炎症条件，细菌必须礼物并非所有的细菌都会引发宿主的炎症反应，事实上，有些细菌是有益的因为它们提供了防止牙周病的保护屏障。它是致病的，如红色复杂的细菌，当以较高的数量存在时，导致宿主的炎症反应。这些细菌包括牙龈卟啉单胞菌（Porphyromonasgingivalis）、嗜酸坦那氏菌（Tannerellaasthia）、齿垢密螺旋体（Treponemadenticola）和梭杆菌属（Fusobacterium 核质因此，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保护肠道微生物群的疗法， needed.机械抗菌治疗以及目前用于治疗这种慢性疾病是广谱的，因此针对致病菌和有益菌。在这里，我们建议使用 amixicile，一种新的全身性治疗剂，其选择性靶向厌氧菌，例如上面列出的那些。抗微生物剂将用于特异性地消耗口腔龈下微生物组的厌氧菌，然后检查微生物组对宿主对处理和对照（未处理）的反应的影响微生物群落使用这种治疗方法，我们将测试amixicile改变微生物组组成的能力。从一个失调的促炎菌群到一个与健康相关的微生物组。培训计划和环境。在此K18培训补助金中，PI将接受理解和使用用于高通量测序数据分析的方法，所述高通量测序数据分析来源于在两个基因组上对微生物组进行测序，和转录组水平以及确定宿主应答的转录组。这些数据将整合以了解宿主反应，这取决于微生物组的组成。的培训将在两名生物信息学专家的指导下进行。提议开展各种活动包括：实验室经验，课程作业，生物信息学分析和在科学会议上的演讲。因此，这项建议将为确保首席研究员在了解应用生物信息学方法以非常全面的方式研究宿主-病原体相互作用。