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Taste Receptor Genetics, The Sinonasal Microbiome and Chronic Rhinosinusitis

味觉感受器遗传学、鼻腔微生物群和慢性鼻窦炎

基本信息

批准号：
10295185
负责人：
Noam A Cohen
金额：
--
依托单位：
PHILADELPHIA VA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-10-01 至 2022-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10295185
关键词：
16S ribosomal RNA sequencing Affect Age Antibiotics Asia Bacteria Bar Codes Bioinformatics Biological Assay Biological Process Cells Chemicals Clinical Collection Data Development Diagnostic tests Disease Ensure Environment Epithelial Event Exposure to Functional disorder Funding Future Gene Family Generations Genetic Genetic Predisposition to Disease Genetic Variation Genomic DNA Genomics Genotype Goals Gram-Negative Bacteria Health Personnel Home environment Human Human Genetics Human Genome Human Microbiome Immune response Individual Iraq Laboratories Lead Length Ligands Measures Medical Microbe Microbial Biofilms Microbiology Mucosal Immunity National Institute on Deafness and Other Communication Disorders Nose Operative Surgical Procedures Outcome Pathology Patients Pattern Persons Phase Phenotype Physiological Predisposition Prognosis Pseudomonas aeruginosa Publishing Race Reaction Receptor Gene Reporting Research Research Institute Research Personnel Resolution Respiration Disorders Risk Role Sampling Scientist Sensory Shapes Signal Pathway Signal Transduction Sinusitis Site Small Interfering RNA Smell Perception Surgeon Surveys Swab Symptoms System Taste Buds Taste Perception Taxonomy Technology Testing Therapeutic Tissues Tongue Variant Vestibule Veterans Virulence Visit Work bactericide base biodefense case control chronic rhinosinusitis disorder risk experimental study fighting genome sciences knock-down microbial microbial community microbial composition microbial genomics microbial signature microbiome microbiome analysis microbiota nasal microbiome nasal microbiota neglect new technology novel operation oral sensory participant enrollment personalized medicine productivity loss quorum sensing ranpirnase receptor receptor expression receptor function response rhinosinusitis sex skills

项目摘要

Chronic rhinosinusitis (CRS) is one of the most common diseases for which people visit a health care provider and receive antibiotics. Recent studies have reported that veterans deployed to the Iraq or Afghan theaters of operation are twice as likely to develop upper respiratory disorders. Veterans of OEF/OIF presenting with post deployment onset of rhinosinusitis undisputedly recount that their symptoms were initiated within several weeks of being deployed supporting an environmental contribution. While bacteria in the sinonasal cavity contribute to the pathophysiology, one puzzle is how microbial species that are more common in people with this disease are also constituents of the normal sinonasal microbiota of healthy people. These phenotypic differences may be due to the inborn genetics of the human host, specifically variation in the taste receptor gene family that are accentuated with exposure to varied environments. Some of these bitter taste receptors, in addition to detecting chemicals on the tongue (taste), also detect secreted bacterial chemicals and trigger the ciliated cells of the sinonasal epithelium to launch an attack. One by-product of this particular physiological system is that people who are not able to taste certain types of bitter compounds may be less able to fight certain bacteria with the same weak sensory signaling pathway. The goal of the proposed research is to combine the expertise of three laboratories to test whether there are interactions between genetic variation of the human host, individual nasal microbiota, and the development of chronic rhinosinusitis: (1) A surgeon scientist with expertise in the medical and surgical treatment of individuals with CRS with access to patients with and without exposure to a foreign environment will ascertain and evaluate the patients. (2) A genomics expert will quantify the human microbiome to the species level using new technologies. (3) A human geneticist and her team will genotype human genomic DNA and evaluate subjects for their ability to taste bitter compounds. The hypothesis is that people with different inborn differences in their ability to detect the chemicals secreted by bacteria will have a different microbiome patterns and susceptibility to CRS. To that end, we will evaluate 60 patients with CRS (cases) and 60 age-, sex, and race-matched healthy controls. This “bitterome” research could explain, at least in part, how bacterial virulence arises in specific individuals and perhaps lead to simple clinical tests to determine how best to personalize treatment.

慢性鼻窦炎 (CRS) 是人们就医的最常见疾病之一并接受抗生素治疗。最近的研究报告称，部署到伊拉克或阿富汗战区的退伍军人手术时发生上呼吸道疾病的可能性是正常人的两倍。 OEF/OIF 退伍军人发表帖子鼻窦炎的发作毫无争议地叙述了他们的症状是在数年内开始的部署数周来支持环境贡献。而鼻腔内的细菌对病理生理学做出贡献的一个难题是，在患有糖尿病的人中更常见的微生物物种如何这种疾病也是健康人正常鼻腔微生物群的组成部分。这些表型差异可能是由于人类宿主的先天遗传造成的，特别是味觉受体的变化随着暴露于不同环境而加重的基因家族。其中一些苦味受体除了检测舌头上的化学物质（味觉）外，还可以检测分泌的细菌化学物质并触发鼻窦上皮的纤毛细胞发起攻击。这种特殊生理学的副产品之一系统的特点是，无法品尝某些类型苦味化合物的人可能不太能够抵抗某些细菌具有相同的微弱感觉信号传导途径。拟议研究的目标是结合三个实验室的专业知识来测试基因变异之间是否存在相互作用人类宿主、个体鼻腔微生物群和慢性鼻窦炎的发展：(1) 外科医生具有 CRS 患者内科和外科治疗专业知识的科学家，能够接触患者无论是否暴露于异国环境，都将确定和评估患者。 (2) 基因组学专家将利用新技术将人类微生物组量化到物种水平。 (3) 人类遗传学家她的团队将对人类基因组 DNA 进行基因分型，并评估受试者尝苦味的能力化合物。该假设是，具有不同先天差异的人检测到的能力存在差异。细菌分泌的化学物质将具有不同的微生物组模式和对 CRS 的易感性。对此最后，我们将评估 60 名 CRS 患者（病例）和 60 名年龄、性别和种族匹配的健康对照。这 “苦味组”研究可以至少部分解释细菌毒力如何在特定个体中产生，以及也许可以进行简单的临床测试来确定如何最好地进行个性化治疗。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Association between the HLA-DQA1 rs1391371 risk allele and chronic rhinosinusitis.

HLA-DQA1 RS1391371风险等位基因和慢性鼻鼻涕之间的关联。

DOI：
10.1002/alr.22960
发表时间：
2022-08
期刊：
INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY
影响因子：
6.4
作者：
Arnold, Monique C.;Poonia, Seerat;Colquitt, Lauren;Lin, Cailu;Civantos, Alyssa;Kohanski, Michael;Adappa, Nithin D.;Palmer, James N.;Reed, Danielle R.;Cohen, Noam A.
通讯作者：
Cohen, Noam A.

Genetics of denatonium-responsive bitter receptors in aspirin-exacerbated respiratory disease.

阿司匹林加剧的呼吸道疾病中地那铵反应性苦味受体的遗传学。

DOI：
10.1002/alr.23077
发表时间：
2023
期刊：
International forum of allergy & rhinology
影响因子：
6.4
作者：
Douglas,JenniferE;Lin,Cailu;Mansfield,CorrineJ;Bell,Katherine;Salmon,MandyK;Kohanski,MichaelA;Adappa,NithinD;Palmer,JamesN;Bosso,JohnV;Reed,DanielleR;Cohen,NoamA
通讯作者：
Cohen,NoamA

Biomarkers in Chronic Rhinosinusitis with Nasal Polyps.