Identifying bacterial regulators of tumorigenesis

识别肿瘤发生的细菌调节因子

• 批准号: 8814012
• 负责人: GRACE Y. CHEN
• 金额: $ 20.27万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-12-08 至 2016-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8814012
• 关键词: Adenomatous Polyposis Coli; Affect; Anti-Inflammatory Agents; Anti-inflammatory; Apoptosis; Azoxymethane; Bacteria; Cancer Etiology; Cancer Model; Chemoprevention; Colitis; Colon Carcinoma; Colorectal Cancer; Communities; Complement; Data; Development; Diet; Epithelial; Equilibrium; Event; Goals; Human; Immune system; Inflammation; Inflammatory Bowel Diseases; Injury; Intestinal Neoplasms; Kinetics; Knock-out; Knockout Mice; Lead; Life; Link; Malignant Neoplasms; Mass Spectrum Analysis; Mediating; Metabolic; Metabolism; Modeling; Mus; Mutation; Patients; Pharmaceutical Preparations; Population; Predisposition; Probiotics; Production; Proteomics; Recurrence; Risk; Signal Pathway; Sodium Dextran Sulfate; Toxic effect; Tumor Promotion; Tumor Suppression; Tumor Suppressor Proteins; United States; Woman; adenoma; base; cancer risk; colon carcinogenesis; colon tumorigenesis; commensal microbes; cytokine; disorder risk; gut microbiota; high risk; inhibitor/antagonist; intestinal homeostasis; member; men; metabolomics; microbiome; mortality; mouse model; novel; pathogen; prevent; public health relevance; tumor; tumor microenvironment; tumorigenesis

 DESCRIPTION (provided by applicant): Colorectal cancer is the third most common cancer in both men and women in the United States. There is growing evidence that pathogenic alterations in the composition of the gut microbiome, also known as dysbiosis, can disrupt intestinal homeostasis, promote inflammation, and increase susceptibility to cancer. In contrast, in the absence of dysbiosis, the gut microbiota largely benefit the host, such as by promoting the development of the gut immune system, facilitating dietary metabolism, and preventing pathogen colonization. However, the function of specific members of the gut microbiota and the mechanism by which the gut microbiota modulates tumor susceptibility have not been clearly defined. Based on our preliminary data, our central hypothesis is that a limited number of bacterial species is capable of reducing colon cancer risk. The purpose of our proposed studies is to further our understanding of the mechanism by which commensal bacteria modulate colon cancer risk using mice models complemented by metabolomics and proteomics. Our long-term goal is to develop a probiotic cocktail of human commensal bacteria that can be used to reduce risk of developing colon cancer, particularly in high risk populations, such as patients with inflammatory bowel disease, familial adenomatous polyposis, or recurrent adenomas.

 描述（由申请人提供）：结直肠癌是美国男性和女性的第三大常见癌症。越来越多的证据表明，肠道微生物组组成的致病性改变，也称为生态失调，可以破坏肠道稳态，促进炎症，并增加对癌症的易感性。相反，在没有生态失调的情况下，肠道微生物群在很大程度上有益于宿主，例如通过促进肠道免疫系统的发育，促进饮食代谢和防止病原体定殖。然而，肠道微生物群特定成员的功能以及肠道微生物群调节肿瘤易感性的机制尚未明确定义。根据我们的初步数据，我们的中心假设是，有限数量的细菌物种能够降低结肠癌风险。我们提出的研究的目的是进一步了解肠道细菌调节结肠癌风险的机制，使用代谢组学和蛋白质组学补充的小鼠模型。我们的长期目标是开发一种人类肠道细菌的益生菌鸡尾酒，可用于降低患结肠癌的风险，特别是在高危人群中，如炎症性肠病，家族性腺瘤性息肉病或复发性腺瘤患者。