The Oral Mycobiome and Risk of Pancreatic Cancer

口腔真菌组和胰腺癌的风险

• 批准号: 10493124
• 负责人: Jiyoung Ahn
• 金额: $ 62.78万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-23 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10493124
• 关键词: 16S ribosomal RNA sequencing; Address; American Cancer Society; Animals; Bacteria; Biological Assay; Biomass; Cancer Burden; Cancer Prevention Study II; Candidiasis; Clinical; Communities; Data; Development; Diagnosis; Dideoxy Chain Termination DNA Sequencing; Disease; Etiology; Exposure to; Flow Cytometry; General Population; Genes; Genetic; Genetic Diseases; Goals; Human; Immune; Immune response; Immunity; Immunohistochemistry; Intervention; Investigation; Joints; Knowledge; Lead; Location; Lymphoid Cell; Malignant Neoplasms; Malignant neoplasm of gastrointestinal tract; Malignant neoplasm of pancreas; Metabolic; Microbe; Myeloid Cells; Natural Immunity; Nature; Nested Case-Control Study; Obesity; Oral; Oral cavity; Outcome; Pancreas; Pancreatic Adenocarcinoma; Pancreatic Diseases; Pancreatitis; Patients; Persons; Phenotype; Prevention; Preventive measure; Process; Prospective Studies; Reporting; Research; Research Design; Risk; Risk Factors; Sampling; Screening for cancer; Smoking; Testing; Tissues; Tumor Immunity; Tumor Tissue; Validation; adaptive immunity; bacteriome; base; cancer prevention; cancer risk; clinical practice; cohort; density; design; disorder risk; experimental study; fungal microbiota; fungus; high risk; improved; individualized prevention; innovation; microbial; microbial host; microbiome; microbiota; multidisciplinary; mycobiome; novel; oral bacteria; oral diagnostics; oral fungal; oral microbial community; oral microbiome; pancreas development; pancreatic neoplasm; pancreatic tumorigenesis; polymicrobial biofilm; prevent; prophylactic; tool; tumor; tumor-immune system interactions

ABSTRACT We hypothesize that oral fungi potentiate pancreas carcinogenesis via the pancreas tumor immune microenvironment. The human oral cavity hosts a diverse microbiota, including bacteria and fungi. Our team has made novel findings that human oral bacterial microbiome is related to risk of pancreas cancer development. In this proposal, we focus on oral fungi (the mycobiome), a “keystone” component of the oral microbiome with the highest biomass. Clinical candidiasis and carriage of a rare candidiasis-related genetic disorder increase risk for pancreas cancer. In our preliminary data, we made novel finding that specific oral fungi are associated with at least 2-fold differentials in pancreatic cancer risk, and those fungi are found in pancreas tumor tissue. We recently reported that fungi experimentally promote pancreas cancer and tumoral immune response in animals. Taken together, these data strongly support our hypothesis. Our ultimate goal is to identify specific oral fungal microbiota in the general population that may be managed to prevent pancreatic cancer. Our specific aims are: 1) to test whether oral fungal microbiome is associated with subsequent risk of pancreatic cancer in a nested case-control study and 2) to test the hypothesis that metabolically active fungi in the pancreas influence tumor immunity. Strengths of this study include a large prospective study design, with oral samples collected prior to cancer development, and state-of-the-art fungal and immune phenotype assays that will accurately and comprehensively characterize fungal composition and immune phenotypes. This is the first investigation of oral and pancreas fungal microbiome and pancreatic cancer risk. Pancreatic cancer is highly lethal and little is known about ways to detect and prevent this disease. We expect to identify specific oral fungi associated with risk of pancreas cancer and to identify fungal—host pancreatic tumor immune response. These outcomes will expand our current limited knowledge on the causes of pancreatic cancer, will help to identify people at high risk for this disease, and may lead to microbial-based prophylactic prevention for pancreatic cancer. Thus, findings may help to rapidly advance our ability to reduce the burden of this highly fatal disease.

抽象的 我们发现口腔真菌通过胰腺肿瘤免疫增强胰腺癌的发生 人类口腔拥有多种微生物群，包括细菌和真菌。 做出了新的发现，即人类口腔细菌微生物组与胰腺癌发展的风险有关。 在这项提案中，我们重点关注口腔真菌（真菌组），它是口腔微生物组的“关键”组成部分 最高的生物量。临床念珠菌病和罕见的念珠菌病相关遗传性疾病的携带会增加患念珠菌病的风险。 在我们的初步数据中，我们发现特定的口腔真菌与胰腺癌有关。 胰腺癌风险至少有两倍的差异，并且我们最近在胰腺肿瘤组织中发现了这些真菌。 报道称，真菌在实验中促进了动物的胰腺癌和肿瘤免疫反应。 这些数据共同有力地支持了我们的假设。 我们的最终目标是确定普通人群中特定的口腔真菌微生物群，并通过这些微生物群的管理 我们的具体目标是：1）测试口腔真菌微生物组是否与预防胰腺癌相关。 在巢式病例对照研究中确定随后发生胰腺癌的风险，并 2) 检验以下假设： 胰腺中代谢活跃的真菌影响肿瘤免疫，这项研究的优点包括很多。 前瞻性研究设计，在癌症发生之前收集口腔样本，以及最先进的真菌 和免疫表型测定，将准确、全面地表征真菌组成和 这是对口腔和胰腺真菌微生物组与胰腺癌的首次研究。 风险。 胰腺癌具有很高的致死率，但我们对检测和预防这种疾病的方法知之甚少。 识别与胰腺癌风险相关的特定口腔真菌，并识别真菌宿主胰腺 这些结果将扩大我们目前对胰腺病因的有限了解。 癌症，将有助于识别患有这种疾病的高危人群，并可能导致基于微生物的预防措施 因此，研究结果可能有助于快速提高我们减轻胰腺癌负担的能力。 这种高度致命的疾病。