Taste Receptor Genetics, The Sinonasal Microbiome and Chronic Rhinosinusitis

味觉感受器遗传学、鼻腔微生物组和慢性鼻窦炎

• 批准号: 10060737
• 负责人: Noam A Cohen
• 金额: --
• 依托单位: PHILADELPHIA VA MEDICAL CENTER
• 依托单位国家: 美国
• 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/10060737
• 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

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）是最常见的疾病之一，人们访问卫生保健提供者 接受抗生素治疗最近的研究报告说，退伍军人部署到伊拉克或阿富汗战区， 手术后患上呼吸道疾病的可能性是手术前的两倍。OEF/OIF退伍军人 部署开始鼻窦炎毫无争议地叙述，他们的症状是在几个 几周的部署支持环境贡献。而鼻腔中的细菌 有助于病理生理学，一个难题是，在患有糖尿病的人中更常见的微生物物种 这种疾病也是健康人的正常鼻窦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学，特别是味觉受体的变异 基因家族，强调与暴露于不同的环境。其中一些苦味受体， 除了检测舌头上的化学物质（味道），还检测分泌的细菌化学物质，并触发 鼻窦上皮的纤毛细胞发动攻击。这种特殊的生理反应的副产品之一 系统是，无法品尝某些类型的苦味化合物的人可能不太能抵抗 某些细菌有着同样微弱的感觉信号通路。拟议研究的目标是 联合收割机结合三个实验室的专业知识，以测试是否有遗传变异之间的相互作用， 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患者医疗和手术治疗专业知识的科学家，可接触患者 无论是否暴露于外部环境，都将确定和评估患者。(2)一套基因组学 专家将使用新技术将人类微生物组量化到物种水平。(3)的人类遗传学专家 她的团队将对人类基因组DNA进行基因分型，并评估受试者品尝苦味的能力。 化合物.这个假设是，具有不同先天差异的人，在他们的能力，以检测 由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。与 最后，我们将评估60例CRS患者（病例）和60例年龄、性别和种族匹配的健康对照。这 “bitterome”研究可以解释，至少部分解释，细菌毒力是如何在特定个体中产生的， 也许会导致简单的临床测试，以确定如何最好地个性化治疗。