ALTERED MICROBIOME IN PANCREATITIS, DIABETES AND PANCREATIC CANCER

胰腺炎、糖尿病和胰腺癌中微生物组的改变

• 批准号: 9045205
• 负责人: WILLIAM E FISHER
• 金额: $ 39.63万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-28 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9045205
• 关键词: Address; Anti-Inflammatory Agents; Anti-inflammatory; Bacteria; Biological Markers; Cancer Etiology; Cell Therapy; Chronic; Clinical; Clinical Data; Clinical Research; Collaborations; Complement; Conduct Clinical Trials; Data; Data Collection; Databases; Detection; Development; Diabetes Mellitus; Diagnosis; Diagnostic Procedure; Disease; Early Diagnosis; Epidemiologic Studies; Epidemiology; Etiology; Feces; Future; Genetic; Genome; Goals; Human Genome; Human Microbiome; Immunologic Receptors; Individual; Inflammation; Inflammatory; Interferon Type II; Interleukin-1; Interleukin-6; Intervention; Investigation; Juice; Lead; Malignant Neoplasms; Malignant neoplasm of pancreas; Measures; Mediating; Medicine; Metabolism; Metagenomics; Methods; Modeling; Molecular; Nuclear; Obesity; Oral; Oral cavity; Organ; Organism; Outcome; PTGS2 gene; Pancreas; Pancreatic Adenocarcinoma; Pancreatic Ductal Adenocarcinoma; Pancreatitis; Pathogenesis; Patients; Pattern; Play; Pre-Clinical Model; Prevention; Prevention strategy; Process; Production; Proteobacteria; Protocols documentation; Research; Risk; Risk Factors; Rodent; Role; STAT3 gene; Saliva; Sample Size; Sampling; Scientist; Site; Smoking; Specimen; Staging; Structure; TLR4 gene; Testing; Tissue Sample; Tissues; Toll-like receptors; Tumor Necrosis Factor-alpha; United States National Institutes of Health; Variant; adiponectin; carcinogenesis; chronic pancreatitis; college; cytokine; design; exome; experience; gene therapy; human genome sequencing; innovation; macrophage; member; microbial; microbiome; microorganism; next generation sequencing; novel strategies; nutrition; pancreatic juice; patient population; prevent; prospective; public health relevance; receptor; research study; trend; tumor

 DESCRIPTION (provided by applicant): Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease with an overall 5-year survival of <5%. Progress in PDAC lags behind other cancers and there is a tremendous need to better understand the etiology of PDAC in order to develop early diagnostic methods and better treatments. Pancreatic carcinogenesis is driven by inflammation. Established risk factors for pancreatic cancer include chronic pancreatitis, diabetes, obesity, and smoking, each associated with an inflammatory mechanism. However, these risk factors do not fully explain the majority of pancreatic cancer cases. E merging evidence suggests that variation in our `other genome'-the collective genome of the microorganisms inhabiting our body, known as the microbiome-may have an even greater role than the human genome variations in the Recent discoveries suggest that bacteria are likely to influence this process by activating immune receptors and perpetuating cancer-associated inflammation. Further investigations are needed to fully understand the interaction between inflammation and the microbiota in the development of this deadly disease. We propose to characterize the microbiota in pancreatic tissue from patients with chronic pancreatitis, chronic pancreatitis and pancreaticogenic (T3cDM) diabetes mellitus, and PDAC using next-generation sequencing protocols. We will also characterize microbiota present in the pancreatic juice, saliva, and stools of the same subjects aiming to find correlative microbial signatures across multiple body sites. The Alkek Center for Metagenomics and Microbiome Research at Baylor College of Medicine (BCM) is a world leader in the study of the microbiome with innovative approaches and thus is ideally suited to coordinate this study. In addition, the Elkins Pancreas Center (EPC) at BCM is eminently suited to be a collaborative member of a national pancreatic research consortium. The EPC will provide access to a large population of patients with pancreatitis, T3cDM, and PDAC, and considerable experience in collaboration for the conduct of clinical trials, sophisticated prospective data collection, and access to a mature tissue repositor for studies proposed by the Consortium. This project is timely and highly relevant to the goals of the NIH Roadmap and the NIH Human Microbiome Project. This novel approach will allow us to create a pathogenic model for pancreatic cancer that will offer innovative strategies for prevention, biomarkers for early detection, and targets for intervention. pathogenesis of cancer.

 描述（由应用提供）：胰腺导管腺癌（PDAC）是一种高度致命的疾病，总5年生存率<5％。其他癌症背后的PDAC滞后的进展，非常需要更好地了解PDAC的病因，以开发早期诊断方法和更好的治疗方法。胰腺癌作用是由炎症驱动的。胰腺癌已建立的危险因素包括慢性胰腺炎，糖尿病，肥胖症和吸烟，每种都与炎症机制有关。但是，这些危险因素不能完全解释大多数胰腺癌病例。 E合并证据表明，我们的“其他基因组” - 居住在我们体内的微生物的集体基因组的变化（称为微生物组）在最近的发现中的作用比人类基因组变异更大，这表明细菌可能通过激活免疫受体和永断癌症与癌症相关的感染来影响这一过程。需要进一步研究以充分了解这种致命疾病发展中感染与菌群之间的相互作用。我们建议表征来自患有慢性胰腺炎，慢性胰腺炎和胰腺生成症（T3CDM）糖尿病的胰腺组织中胰腺组织中的微生物群，并使用下一代测序方案使用PDAC。我们还将表征胰汁，唾液和同一受试者的粪便中存在的微生物群，旨在在多个身体部位找到相关的微生物特征。贝勒医学院（BCM）的宏基因组学和微生物组研究中心是通过创新方法研究微生物组研究的世界领导者，因此非常适合协调这项研究。此外，BCM的Elkins Pancreas Center（EPC）紧急是国家胰腺研究联盟的合作成员。 EPC将提供大量患有胰腺炎，T3CDM和PDAC患者的访问权限，并在合作中进行临床试验，复杂的前瞻性数据收集以及访问该联盟提出的研究的成熟组织存储库的合作经验。该项目与NIH路线图和NIH人类微生物组项目的目标及时且高度相关。这种新颖的方法将使我们能够为胰腺癌创建致病模型，该模型将为预防提供创新的策略，生物标志物的早期检测和干预靶标。癌症的发病机理。