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

基本信息

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
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/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

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

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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.

慢性鼻塞炎（CRS）是人们参观医疗保健提供者的最常见疾病之一并接受抗生素。最近的研究报道，退伍军人部署到伊拉克或阿富汗剧院患有上呼吸道疾病的可能性是两倍。 OEF/OIF的退伍军人出现毫无疑问的鼻孔炎的部署发作，表明它们的症状是在几个症状开始的部署的数周支持环境贡献。而鼻窦腔中的细菌有助于病理生理学，一个难题是在患有患者中更常见的微生物物种这种疾病也是健康人正常的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，特别是味觉接收器的变化强调各种环境的基因家族。这些苦味受体中的一些，在除了检测舌头上的化学物质（口味），还检测到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。该特定生理学的一个副产品系统是无法品尝某些类型的苦味的人可能不太能够打架具有相同弱的感觉信号通路的某些细菌。拟议研究的目的是结合三个实验室的专业知识，以测试是否存在相互作用人类宿主，单个鼻菌群和慢性鼻鼻炎的发展：（1）外科医生科学家具有CRS患者的医学和外科治疗方面的专业知识在有或没有外国环境的情况下，将确定和评估患者。（2）基因组学专家将使用新技术将人类微生物组量化为物种水平。（3）人类遗传学家她的团队将基因类型的人类基因组DNA并评估受试者的苦味能力化合物。假设是，在检测能力的能力上有不同的天生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的敏感性。为此最后，我们将评估60例CR（病例）和60岁，性别和种族匹配的健康对照患者。这 “ Bitterome”研究至少可以解释细菌病毒在特定个体中如何产生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。