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) 是人们就医的最常见疾病之一 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。 手术后出现上呼吸道疾病的可能性是 OEF/OIF 退伍军人的两倍。 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 数周的部署支持环境贡献，而鼻腔中的细菌。 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。 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 这些苦味受体中的一些基因家族随着暴露于不同的环境而加重。 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，这是这种特殊生理学的副产品。 系统的特点是，无法品尝某些类型的苦味化合物的人可能不太能够抵抗 某些具有相同弱感觉信号通路的细菌本研究的目标是 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 (2) 基因组学 (3) 人类遗传学家 她和她的团队将对人类基因组 DNA 进行基因分型并评估受试者的苦味能力 假设不同的人检测化合物的能力存在先天差异。 细菌分泌的化学物质具有不同的微生物组模式和对 CRS 的易感性。 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。 “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。