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 我们假设口服真菌通过胰腺肿瘤免疫增强胰腺癌发生 微环境。人口腔占据了潜水员菌群，包括细菌和真菌。我们的团队有 做出了新的发现，即人口腔细菌微生物组与胰腺癌发展的风险有关。在 该建议，我们专注于口服真菌（Mycobiome），这是口服微生物组的“基石”组成部分 最高生物量。稀有念珠菌病的临床念珠菌病和与遗传疾病的携带者增加了风险 胰腺癌。在我们的初步数据中，我们发现了特定的口服真菌与AT相关的新颖新颖 胰腺癌风险中至少有2倍的差异，以及在胰腺肿瘤组织中发现的真菌。我们最近 报道了真菌通过实验促进胰腺癌和动物的肿瘤免疫反应。拍摄 这些数据共同支持我们的假设。 我们的最终目标是确定一般人群中特定的口服真菌微生物群 预防胰腺癌。我们的具体目的是：1）测试口服真菌微生物组是否与 随后在嵌套病例对照研究中胰腺癌的风险，2）检验以下假设。 胰腺中代谢活性真菌会影响肿瘤免疫学。这项研究的优势包括大型 前瞻性研究设计，在癌症发展之前收集了口头样品，以及最先进的真菌 和免疫表型测定法，将准确，全面地表征真菌组成和 免疫表型。这是口服和胰腺真菌微生物组和胰腺癌的第一笔投资 风险。 胰腺癌是高度致命的，对检测和预防这种疾病的方法知之甚少。我们期望 确定与胰腺癌风险相关的特定口服真菌并识别真菌 - 卫生胰腺 肿瘤免疫反应。这些结果将扩大我们目前对胰腺原因的有限知识 癌症，将有助于确定这种疾病高风险的人，并可能导致基于微生物的预防性 预防胰腺癌。那就发现可能有助于迅速提高我们减少燃烧的能力 这种高度致命的疾病。