DYSBIOTIC MICROBIOME IN PANCREATITIS, DIABETES, AND PANCREATIC CANCER

胰腺炎、糖尿病和胰腺癌中的微生物菌群失调

• 批准号: 10684449
• 负责人: WILLIAM E FISHER
• 金额: $ 10万
• 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 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10684449
• 关键词: Affect; Bacteria; Biodiversity; Cancer Etiology; Clinical; Clinical Data; Clinical Trials; Cohort Studies; Collaborations; Conduct Clinical Trials; DNA; Data; Data Collection; Development; Diabetes Mellitus; Diagnosis; Diagnostic Procedure; Disease; Disease Marker; Disease Progression; Disease susceptibility; Early Diagnosis; Early treatment; Enrollment; Etiology; Feces; Firmicutes; Functional disorder; Genome; Goals; Growth; Human Genome; Human Microbiome; Immune response; Immunologic Receptors; Immunotherapy; Inflammation; Inflammatory; Intervention; Investigation; Lead; Leadership; Light; Malignant Neoplasms; Malignant neoplasm of pancreas; Medicine; Metabolism; Metagenomics; Methods; Modeling; National Institute of Diabetes and Digestive and Kidney Diseases; Nature; Obesity; Oral; Oral cavity; Organism; Pancreas; Pancreatic Ductal Adenocarcinoma; Pancreatitis; Pathogenesis; Pathogenicity; Patients; Pattern; Periodontitis; Persons; Porphyromonas gingivalis; Prevention; Prevention strategy; Process; Prognostic Marker; Proteobacteria; Protocols documentation; Research; Resistance; Risk; Risk Factors; Role; Saliva; Sampling; Scientist; Site; Smoking; Streptococcus mitis; Survival Rate; Taxonomy; Testing; Therapeutic; Time; Tissue Banks; Tissue Sample; Tissues; Tumor Tissue; United States National Institutes of Health; Variant; biobank; biomarker discovery; chemotherapeutic agent; chronic pancreatitis; college; commensal bacteria; cost; design; dysbiosis; early detection biomarkers; experience; experimental study; gut dysbiosis; host microbiome; human genome sequencing; innovation; insight; member; microbial; microbial signature; microbiome; microbiome research; microbiota; microorganism; next generation sequencing; novel strategies; nutrition; oral microbiome; oral pathogen; pancreas development; pancreatic neoplasm; pancreatic tumorigenesis; patient population; prognostic method; prospective; recruit; repository; systemic inflammatory response; treatment strategy; tumor; tumor-immune system interactions

Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease with an overall 5-year survival of <9%. 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. Emerging 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 pathogenesis of cancer. 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 saliva, stool, and pancreatic tissue from patients with chronic pancreatitis and PDAC using next-generation sequencing protocols. We will characterize microbiota present in the saliva, stool, and pancreatic tissue from each subject 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 and PDAC, and considerable experience in collaboration for the conduct of clinical trials, sophisticated prospective data collection, and access to a mature tissue repository 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 chronic pancreatitis and pancreatic cancer that will offer innovative strategies for prevention, biomarkers for early detection, and targets for intervention.

胰腺导管腺癌（PDAC）是一种高度致命的疾病，总5年生存率<9％。 其他癌症背后的PDAC滞后的进展，并且有巨大的需求可以更好地理解病因 PDAC的生命是为了开发早期诊断方法和更好的治疗方法。胰腺癌是 受炎症驱动。胰腺癌已建立的危险因素包括慢性胰腺炎，糖尿病， 肥胖和吸烟，每种都与炎症机制有关。但是，这些风险因素没有 充分解释大多数胰腺癌病例。新兴的证据表明，我们的其他差异 基因组 - 居住在我们体内的微生物的集体基因组，被称为微生物组 - 可能 在癌症的发病机理中，具有比人类基因组变异更大的作用。最近的发现 表明细菌可能通过激活免疫受体和永久性影响这一过程 与癌症相关的保险。需要进一步研究以充分了解 炎症和这种致命疾病发展的菌群。 我们建议从慢性患者的唾液，粪便和胰组织中的微生物群来表征 胰腺炎和PDAC使用下一代测序方案。我们将表征存在的微生物群 来自每个受试者的唾液，凳子和胰组织，旨在寻找相关的微生物特征 多个身体部位。 贝勒医学院（BCM）的宏基因组学和微生物组研究中心是一个 通过创新方法研究微生物组的世界领导者，因此非常适合协调 这项研究。此外，BCM的Elkins Pancreas Center（EPC）非常适合合作 国家胰腺研究联盟的成员。 EPC将提供大量人口的访问 患有胰腺炎和PDAC的患者，以及在临床上进行的丰富经验 试验，先进的前瞻性数据收集以及访问成熟的组织存储库的研究 由财团。 该项目与NIH路线图和NIH人类微生物组的目标及时且高度相关 项目。这种新颖的方法将使我们能够为慢性胰腺炎和胰腺造成病原模型 将为预防提供创新策略，早期检测的生物标志物以及目标的癌症 干涉。