Interactive Omics: Black raspberry metabolites and the oral microbiome in smokers

交互式组学：黑树莓代谢物和吸烟者的口腔微生物组

• 批准号: 9084715
• 负责人: STEVEN K CLINTON
• 金额: $ 15.75万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9084715
• 关键词: Adherence; Affect; American; Anthocyanins; Apoptosis; Area; Bacteria; Bioinformatics; Biological; Biological Availability; Biological Markers; Cancer Patient; Cell model; Characteristics; Clinical Research; Communities; Diagnosis; Disease; Dose; Ecosystem; Epidemic; Exposure to; Food; Fruit; Future; Gene Expression Profile; Goals; Health; High Pressure Liquid Chromatography; Hour; Inflammation; Inflammatory Response; Interdisciplinary Study; Malignant Neoplasms; Mediating; Metabolism; Methodology; Microbial Biofilms; Molecular; Molecular Models; Operative Surgical Procedures; Oral; Oral cavity; Oral mucous membrane structure; Outcome Study; Patients; Phase III Clinical Trials; Phytochemical; Play; Population; Predisposition; Prevention strategy; Raspberries; Recurrence; Research; Research Design; Resolution; Retinoids; Rodent Model; Role; Saliva; Sensory; Shotguns; Smoker; Smoking; System; Testing; TimeLine; Tobacco; Toxic effect; Treatment outcome; attenuation; base; disorder prevention; high risk; liquid chromatography mass spectrometry; malignant mouth neoplasm; metabolomics; metagenomic sequencing; microbial; microorganism interaction; molecular modeling; never smoker; novel; oral bacteria; oral biofilm; oral carcinogenesis; oral microbiome; outcome forecast; pathogenic bacteria; point-of-care diagnostics; pre-clinical; smoking cessation; tobacco exposure; transcriptome sequencing

Abstract Oral cancer affects nearly 300,000 Americans each year and is a serious health concern due to its poor prognosis and high recurrence rate. Moreover, the worldwide tobacco epidemic is leading to thousands of new cases of oral cancer being diagnosed each year. Targeting preventive strategies for those at highest risk for oral cancer due to tobacco exposure is thus a high priority. Our ultimate goal is to employ a food-based cancer preventive strategy for high-risk populations that allows excellent long-term adherence and efficacy. The oral cavity is an open microbial ecosystem that plays host to over 700 species of bacteria that form healthcompatible communities called biofilms. We have previously demonstrated that these biofilms are rapidly enriched for pathogenic bacteria in smokers, resulting in an early hyper-inflammatory response. Furthermore, smoking cessation reverses this pathogenic bacterial recolonization, demonstrating that smoking has a direct effect on the oral microbiome and may increase the risk for oral carcinogenic processes by disturbing normal host-bacterial interactions. Therefore, our central hypothesis is that a critical bi-directional interaction exists between oral bacteria and phytochemical-rich black raspberry food products, which ultimately results in attenuation of inflammation and amelioration of disease. First, we will determine the effect of black raspberry phytochemicals (BRBs) on community dynamics within oral biofilms by combining a longitudinal clinical study design and a novel BRB delivery system (BRB nectar) with the resolution provided by shotgun metagenomic sequencing and computational bioinformatics. Next, we will examine the effect of oral bacterial communities on metabolism of BRBs in current and never smokers. Targeted HPLC-MS/MS analysis will be used to identify known phenolics and metabolites, while untargeted UHPLC Q-TOF metabolome analysis will identify novel compounds. Finally, we will evaluate the efficacy of BRBs and their metabolites in reversing the effect of smoking on oral host-microbial interactions by combining a longitudinal clinical study design with a novel, high-throughput “dual RNA-Seq” methodology to simultaneously quantify both oral bacterial and oral mucosal transcriptome changes before and after exposure to BRB nectar. Following the successful completion of these Specific Aims, we will demonstrate for the first time the ability of BRBs to mitigate pathogenic metabolic process and gene expression patterns induced by cigarette smoke in a manner that supports oral carcinogenesis prevention strategies.

摘要 口腔癌每年影响近300，000美国人，并且由于其不良的生物学特性而成为严重的健康问题。 复发率高。此外，世界范围内的烟草流行正在导致成千上万的新的 口腔癌的诊断每年。针对高危人群的预防战略 因此，由烟草暴露引起的口腔癌是一个高度优先事项。我们的最终目标是利用一种基于食物的癌症 高风险人群的预防策略，可以实现出色的长期依从性和有效性。口腔 体腔是一个开放的微生物生态系统，它是700多种细菌的宿主， 称为生物膜。我们以前已经证明，这些生物膜迅速 富含吸烟者体内的致病菌，导致早期炎症反应。此外，委员会认为， 戒烟逆转了这种致病性细菌的繁殖，表明吸烟有直接的 对口腔微生物组的影响，并可能通过干扰正常的 宿主-细菌相互作用因此，我们的中心假设是关键的双向互动 存在于口腔细菌和富含植物化学物质的黑树莓食品之间， 导致炎症的减弱和疾病的改善。首先，我们将确定 黑树莓植物化学物质（BRBs）对口腔生物膜内群落动态的影响， 纵向临床研究设计和一种新的BRB输送系统（BRB nectar），其分辨率为 鸟枪法宏基因组测序和计算生物信息学。接下来，我们将研究口服 细菌群落对当前和从不吸烟者BRB代谢的影响。靶向HPLC-MS/MS分析 将用于鉴定已知的酚类化合物和代谢物，而非靶向UHPLC Q-TOF代谢物组 分析将鉴定新的化合物。最后，我们将评估BRBs及其代谢产物在 通过结合纵向临床研究逆转吸烟对口腔宿主-微生物相互作用的影响 设计了一种新的，高通量的“双RNA-Seq”方法，同时定量两种口服 暴露于BRB花蜜前后细菌和口腔粘膜转录组的变化。后 成功完成这些特定目标后，我们将首次展示BRB的能力， 减轻香烟烟雾诱导的致病代谢过程和基因表达模式， 支持口腔癌预防策略。