E-cigarettes and oral wound healing: an integrated omics approach

电子烟和口腔伤口愈合：综合组学方法

• 批准号: 10680053
• 负责人: Michelle Lee Scott
• 金额: $ 5.35万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10680053
• 关键词: Aerosols; Affect; Alcohols; Anaerobic Bacteria; Animals; Area; Bacteria; Bilateral; Biological; Biopsy Specimen; Blood flow; Cancerous; Case Study; Cicatrix; Cigarette; Clinical; Clinical Research; Complex; Cutaneous; Data; Devices; Diet; Ecosystem; Electronic Nicotine Delivery Systems; Electronic cigarette; Environment; Epithelium; Event; Failure; Fibroblasts; Fibrosis; Fistula; Flavoring; Glycerol; Goals; Granuloma; Growth; Health; Health Care Costs; Health Personnel; Health Policy; Heating; Homeostasis; Human; Immune; Impaired wound healing; Impairment; In Vitro; Infection; Inflammation; Inflammatory Response; Intervention Studies; Keloid; Knowledge; Lead; Marketing; Mastectomy; Measurable; Measures; Mediating; Medical; Microbe; Modeling; Molecular; Morbidity - disease rate; Mucous Membrane; Necrosis; Nicotine; Operative Surgical Procedures; Oral; Oral cavity; Oral health; Organ Transplantation; Outcome; Pain; Patients; Perforation; Periodontitis; Persons; Pharmaceutical Preparations; Play; Postoperative Period; Procedures; Process; Propylene Glycols; Public Health; Reconstructive Surgical Procedures; Rehabilitation therapy; Research; Research Design; Risk Assessment; Role; Skin wound healing; Smoking; Testing; Time; Tissue Grafts; Tissues; Tobacco; United States; Virulence; Voice; Wound models; biomarker identification; case control; clinical effect; combustible cigarette; cytokine; dysbiosis; electronic cigarette use; experience; experimental study; healing; host-microbe interactions; in vitro Model; in vivo; metabolomics; metatranscriptomics; microbial; microbial host; microbiome; mortality; multilevel analysis; multiple omics; non-healing wounds; oral microbiome; pathogen; response; smoking cessation; success; tool; transcriptomics; wound; wound closure; wound healing

Project Abstract Impaired wound healing is both a financial and medical burden for patients. In the oral cavity, early and complete wound closure is a critical determinant of the success of surgical treatments ranging from extractions to grafting. Oral health is mediated by a diverse microbial ecosystem, and there is evidence that dysbiosis in this microbiome can contribute to poor wound healing outcomes. Wound healing outcomes can be influenced by a wide range of factors, one of which might be e-cigarettes, also referred to as electronic nicotine delivery systems (ENDS). These devices deliver an aerosol mixture by heating propylene glycol, glycerol, nicotine, additives and flavorings. Although concerns have been voiced about these devices, usage continues to increase, partially as a result of being marketed as a safer alternative to traditional cigarettes and as a smoking cessation aid. However, evidence is emerging to suggest that ENDS negatively impact wound healing outcomes. These results combined with an increase in usage emphasize that there is an urgent need to investigate the biological effects of ENDS. Our preliminary data has shown that ENDS exposure increases the virulence potential of the oral microbiome and elicits a brisk proinflammatory response in ENDS users. Therefore, we hypothesize that ENDS promote the growth of anaerobic bacteria in the oral cavity, prolonging post-surgical inflammation and resulting in delayed oral wound healing and time to wound closure. We propose to test this hypothesis by combining an integrated ‘omics’ approach with a clinical study design and validate this with an in vitro model that recapitulates oral wound healing events. This approach will measure the clinical effects of ENDS use on oral wound healing, as well as identify the mechanisms behind these clinical events. In Aim 1, we will quantify the clinical impacts of ENDS on oral wound healing using a longitudinal case-control intervention study. Biopsy samples will be utilized for host transcriptomics, metatranscriptomics and metabolomics and the time to wound closure will be measured. In Aim 2, we will validate these results using an in vitro model of cutaneous wound healing and explore the mechanisms by which ENDS impact wound healing events. Since successful wound healing relies on oral microbial homeostasis, we will combine host epithelium with an underlying fibroblast layer and construct of core microbes. Host transcriptomics, metatranscriptomics and metabolomics will be analyzed and validated with RT-qPCR. By combining the complexity of a clinical model with a highly controlled in vitro experiment, the proposed study will provide important evidence to understand the role of ENDS in disrupting host microbial homeostasis, provide new understanding of the complexities of ENDS on oral wound healing and establish indicators of ENDS associated host microbial dysbiosis.

项目摘要 在口腔中，伤口愈合受损对患者来说既是经济负担也是医疗负担。 伤口闭合是从拔牙到移植等手术治疗成功的关键决定因素。 口腔健康是由多样化的微生物生态系统介导的，有证据表明该微生物组中存在菌群失调 可能导致伤口愈合结果不佳 伤口愈合结果可能受到多种因素的影响。 其中之一可能是电子烟，也称为电子尼古丁输送系统（ENDS）。 这些设备通过加热丙二醇、甘油、尼古丁、添加剂和调味剂来提供气雾混合物。 尽管人们对这些设备表示担忧，但使用量仍在持续增加，部分原因是 被作为传统香烟的更安全替代品和戒烟辅助品进行销售，但有证据表明。 越来越多的证据表明，ENDS 对伤口愈合结果产生负面影响。 使用量的增加强调迫切需要研究电子尼古丁传送系统的生物效应。 初步数据表明，电子烟接触电子烟会增加口腔微生物组的潜在毒力， 在 ENDS 使用者中引起快速的促炎症反应，因此，我们能够促进 ENDS 的使用。 口腔内厌氧菌的生长，延长术后炎症并导致延迟 我们建议通过结合综合测试这一假设。 采用临床研究设计的“组学”方法，并通过重现口腔伤口的体外模型进行验证 该方法将衡量 ENDS 使用对口腔伤口愈合以及愈合事件的临床效果。 确定这些临床事件背后的机制 在目标 1 中，我们将量化 ENDS 对临床的影响。 使用纵向病例对照干预研究的口腔伤口愈合将用于宿主。 将测量转录组学、宏转录组学和代谢组学以及伤口闭合的时间。 2、我们将使用皮肤伤口愈合的体外模型验证这些结果并探索其机制 由于成功的伤口愈合依赖于口腔微生物，因此结束伤口影响愈合事件。 为了实现稳态，我们将宿主上皮与下面的成纤维细胞层和核心微生物的构建体结合起来。 将通过 RT-qPCR 分析和验证宿主转录组学、宏转录组学和代谢组学。 将临床模型的复杂性与高度控制的体外实验相结合，拟议的研究将 提供重要证据来了解 ENDS 在破坏宿主微生物稳态方面的作用，提供 对 ENDS 对口腔伤口愈合复杂性的新认识并建立 ENDS 指标 相关宿主微生物失调。