The Oral Mycobiome and Risk of Pancreatic Cancer

摘要 我们假设口腔真菌通过胰腺肿瘤免疫增强胰腺癌的发生， 微环境人类口腔中有多种微生物群，包括细菌和真菌。我们的团队已被 人类口腔细菌微生物组与胰腺癌发展风险有关的新发现。在 在这个建议中，我们专注于口腔真菌（菌群），这是口腔微生物组的“基石”组成部分， 最高的生物量临床念珠菌病和携带一种罕见的念珠菌相关遗传性疾病增加了 胰腺癌在我们的初步数据中，我们有了新的发现，即特定的口腔真菌与at 胰腺癌风险的至少2倍差异，并且这些真菌在胰腺肿瘤组织中被发现。我们最近 报道，真菌实验促进胰腺癌和肿瘤免疫反应的动物。采取 总之，这些数据有力地支持了我们的假设。 我们的最终目标是确定一般人群中特定的口腔真菌微生物群， 预防胰腺癌。我们的具体目标是：1）测试口腔真菌微生物组是否与 巢式病例对照研究中胰腺癌的后续风险; 2）检验假设， 胰腺中的代谢活性真菌影响肿瘤免疫。这项研究的优势包括一个大的 前瞻性研究设计，在癌症发生前收集口腔样本， 和免疫表型测定，将准确和全面地表征真菌组成， 免疫表型这是首次对口腔和胰腺真菌微生物组与胰腺癌的研究 风险 胰腺癌是高度致命的，人们对检测和预防这种疾病的方法知之甚少。我们预计 确定与胰腺癌风险相关的特定口腔真菌，并确定真菌宿主胰腺癌， 肿瘤免疫反应这些结果将扩大我们目前对胰腺癌病因的有限认识。 癌症，将有助于确定这种疾病的高风险人群，并可能导致基于微生物的预防性治疗。 预防胰腺癌。因此，这些发现可能有助于迅速提高我们减轻肥胖负担的能力。 这种高度致命的疾病。

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.