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: 9762009
• 负责人: STEVEN K CLINTON
• 金额: $ 31.63万
• 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 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9762009
• 关键词: Adherence; Affect; American; Anthocyanins; Apoptosis; Area; Bacteria; Bioinformatics; Biological; Biological Availability; Cancer Patient; Cell model; Characteristics; Clinical Research; Communities; Development; 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; Operative Surgical Procedures; Oral; Oral cavity; Oral mucous membrane structure; Outcome Study; Pathogenicity; Patients; Pharmacology; Phase III Clinical Trials; Phenols; Phytochemical; Play; Predisposition; Prevention strategy; Process; Raspberries; Recurrence; Research; Research Design; Resolution; Retinoids; Risk; Rodent Model; Role; Saliva; Sensory; Shotguns; Smoker; Smoking; System; Testing; Time; TimeLine; Tobacco; Toxic effect; Treatment outcome; attenuation; bacterial community; base; carcinogenicity; cigarette smoke-induced; disorder prevention; high risk; high risk population; host-microbe interactions; liquid chromatography mass spectrometry; malignant mouth neoplasm; metabolome; metabolomics; metagenomic sequencing; microbial; molecular marker; molecular modeling; never smoker; novel; oral bacteria; oral biofilm; oral carcinogenesis; oral microbiome; outcome forecast; pathogenic bacteria; point-of-care diagnostics; pre-clinical; public health relevance; smoking cessation; tobacco exposure; transcriptome; transcriptome sequencing

DESCRIPTION (provided by applicant): 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 health- compatible 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.

描述（由申请人提供）：口腔癌每年影响近 300,000 名美国人，由于其预后不良和复发率高，是一个严重的健康问题。此外，全球烟草流行导致每年诊断出数以千计的新口腔癌病例。因此，针对因烟草暴露而患口腔癌风险最高的人群制定预防策略是当务之急。我们的最终目标是针对高危人群采用基于食物的癌症预防策略，以实现良好的长期依从性和疗效。口腔是一个开放的微生物生态系统，拥有 700 多种细菌，这些细菌形成了称为生物膜的健康相容性群落。我们之前已经证明，这些生物膜在吸烟者体内迅速富集致病菌，导致早期的过度炎症反应。此外，戒烟可逆转这种致病细菌的重新定植，这表明吸烟对口腔微生物群有直接影响，并可能通过扰乱正常的宿主-细菌相互作用来增加口腔致癌过程的风险。因此，我们的中心假设是口腔细菌和富含植物化学物质的黑树莓食品之间存在关键的双向相互作用，最终导致炎症减轻和疾病改善。首先，我们将通过纵向临床研究设计和新型 BRB 递送系统（BRB 花蜜）与鸟枪法宏基因组测序和计算生物信息学提供的分辨率相结合，确定黑树莓植物化学物质 (BRB) 对口腔生物膜内群落动态的影响。接下来，我们将研究口腔细菌群落对当前吸烟者和从不吸烟者的 BRB 代谢的影响。靶向 HPLC-MS/MS 分析将用于鉴定已知的酚类和代谢物，而非靶向 UHPLC Q-TOF 代谢组分析将鉴定新化合物。最后，我们将通过将纵向临床研究设计与新颖的高通量“双 RNA 测序”方法相结合，同时量化口腔宿主和微生物的相互作用，评估 BRB 及其代谢物在逆转吸烟对口腔宿主微生物相互作用的影响方面的功效。接触 BRB 花蜜前后细菌和口腔粘膜转录组的变化。在成功完成这些具体目标后，我们将首次证明 BRB 能够以支持口腔癌预防策略的方式减轻香烟烟雾诱导的致病代谢过程和基因表达模式。

项目成果

Application of a low polyphenol or low ellagitannin dietary intervention and its impact on ellagitannin metabolism in men.

• DOI: 10.1002/mnfr.201600224
• 发表时间: 2017-03
• 期刊: Molecular nutrition & food research
• 影响因子: 5.2
• 作者: Roberts KM;Grainger EM;Thomas-Ahner JM;Hinton A;Gu J;Riedl KM;Vodovotz Y;Abaza R;Schwartz SJ;Clinton SK
• 通讯作者: Clinton SK

STAT4 is required for the generation of Th1 and Th2, but not Th17 immune responses during monophosphoryl lipid A adjuvant activity.

在单磷酰脂质 A 佐剂活性期间，STAT4 是 Th1 和 Th2 生成所必需的，但不是 Th17 免疫反应所必需的。

• DOI: 10.1093/intimm/dxw038
• 发表时间: 2016
• 期刊: International immunology
• 影响因子: 4.4
• 作者: Varikuti,Sanjay;Oghumu,Steve;Natarajan,Gayathri;Kimble,Jennifer;Sperling,RachelH;Moretti,Ellen;Kaplan,MarkH;Satoskar,AbhayR
• 通讯作者: Satoskar,AbhayR

Meglumine antimoniate is more effective than sodium stibogluconate in the treatment of cutaneous leishmaniasis.

• DOI: 10.3109/09546634.2015.1054778
• 发表时间: 2016
• 期刊: The Journal of dermatological treatment
• 作者: Yesilova Y;Surucu HA;Ardic N;Aksoy M;Yesilova A;Oghumu S;Satoskar AR
• 通讯作者: Satoskar AR

Topical treatment with nanoliposomal Amphotericin B reduces early lesion growth but fails to induce cure in an experimental model of cutaneous leishmaniasis caused by Leishmania mexicana.

在由墨西哥利什曼原虫引起的皮肤利什曼病实验模型中，纳米脂质体两性霉素 B 的局部治疗可减少早期病变生长，但无法诱导治愈。

• DOI: 10.1016/j.actatropica.2017.06.004
• 发表时间: 2017
• 期刊: Acta tropica
• 影响因子: 2.7
• 作者: Varikuti,Sanjay;Oghumu,Steve;Saljoughian,Noushin;Pioso,MarissaS;Sedmak,BrenE;Khamesipour,Ali;Satoskar,AbhayR
• 通讯作者: Satoskar,AbhayR

Host-mediated Leishmania donovani treatment using AR-12 encapsulated in acetalated dextran microparticles.

• DOI: 10.1016/j.ijpharm.2016.01.004
• 发表时间: 2016-02-29
• 期刊: International journal of pharmaceutics
• 影响因子: 5.8
• 作者: Collier MA;Peine KJ;Gautam S;Oghumu S;Varikuti S;Borteh H;Papenfuss TL;Sataoskar AR;Bachelder EM;Ainslie KM
• 通讯作者: Ainslie KM