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The Oral Mycobiome and Risk of Pancreatic Cancer

口腔真菌组和胰腺癌的风险

基本信息

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
项目类别：
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

项目摘要

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.

摘要