Elucidating the role of gut microbiota in colitis-associated colorectal cancer

阐明肠道微生物群在结肠炎相关结直肠癌中的作用

基本信息

批准号：
10564074
负责人：
Ru Chen
金额：
$ 64.91万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-01-01 至 2027-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10564074
关键词：
Affect Animal Model Apoptosis Bacteria Bacterial Genes Bioinformatics Biological Biological Models Biopsy Cancer Detection Chronic Clinical Clinical Research Colitis associated colorectal cancer Colon Colorectal Cancer DNA Damage Development Disease Enzymes Epithelium Event Genes Genomic Instability Gut Mucosa Human Immune response In Vitro Individual Inflammation Inflammatory Inflammatory Bowel Diseases Integration Host Factors Intestinal Cancer Investigation Knowledge Laboratories Light Longitudinal Studies Malignant Neoplasms Metabolism Modeling Molecular Mucous Membrane Mus Organoids Oxidative Stress Pathogenesis Pathway interactions Patients Proliferating Proteome Proteomics Rectum Research Resources Risk Role Sampling Signal Pathway Specimen Structure Study models Surface System Systems Biology Taxonomy Techniques Technology Ulcerative Colitis Work cancer therapy carcinogenesis colitis associated cancer colorectal cancer prevention colorectal cancer risk design dextran sulfate sodium induced colitis dysbiosis fecal microbiota gut microbes gut microbiome gut microbiota human microbiota in vivo innovation interest metaproteomics microbial microbial community microbiome microbiome composition microbiota microbiota profiles mouse model mucosal microbiota new technology novel diagnostics novel strategies novel therapeutic intervention phosphoproteomics protein expression rectal response statistics tool translational potential tumor progression tumorigenic

项目摘要

Abstract Patients with ulcerative colitis (UC), an inflammatory bowel disease (IBD), have an increased risk of developing colitis-associated colorectal cancer (CAC). Human gut microbiome composition has recently been associated with a wide array of diseases, including IBD and colorectal cancer. Studies have shown that gut microbiota could influence colon epithelium to initiate or promote colorectal cancer development directly or indirectly. However, little is known on the structure and function of the microbiota in CAC and how they implicate the development of CAC at the molecular level. In this study, we will investigate the role of microbiota in the development of CAC, as well as the molecular events underlying the interplay of microbiota and host response. The project builds upon our previous studies in examining the genomic instabilities and proteome alterations in the colon epithelium during the pathogenesis of IBD-CAC, and will focus on the mechanistic and functional involvement of the microbiome and their components in the modulation (by protective bacteria) or activation (by tumorigenic bacteria) of CAC development. Specifically, we will investigate the implication of mucosa- associated microbiota in CAC by an integrated approach using three model systems, including clinical specimens (Aim 1), in vitro microbial cultivation and organoid models (Aim 2), and in vivo mouse model (Aim 3). Our integrative, state-of-the-art approach will characterize the composition, functional genes and pathways of the microbiome implicated in CAC, and the impact of microbiota on colon mucosa. By studying the gut microbiota and its interplay with the colon host using novel approaches and cutting-edge technology, our study has significant translational potential that could lead to establishing the gut microbiome as predictors of CAC risk and aid in developing approaches for CAC prevention and detection in IBD patients.

抽象的溃疡性结肠炎患者（UC），一种炎症性肠病（IBD），患有增加的风险结肠炎相关的结直肠癌（CAC）。人类肠道微生物组组成最近已关联有多种疾病，包括IBD和大肠癌。研究表明肠道菌群可能会影响结肠上皮，直接或间接地启动或促进结直肠癌的发展。但是，在CAC中微生物群的结构和功能上几乎没有知道在分子水平上开发CAC。在这项研究中，我们将研究微生物群在 CAC的发展以及菌群相互作用和宿主反应相互作用的分子事件。该项目以我们先前研究基因组不稳定性和蛋白质组改变的研究为基础 IBD-CAC发病机理期间的结肠上皮，将集中于机械和功能微生物组及其成分参与调制（通过保护细菌）或激活（由肿瘤细菌）CAC发育。具体而言，我们将研究粘膜的含义使用三种模型系统（包括临床标本（AIM 1），体外微生物培养和器官模型（AIM 2）和体内小鼠模型（AIM 3）。我们的整合，最先进的方法将表征组成，功能基因和途径与CAC有关的微生物组以及微生物群对结肠粘膜的影响。通过研究肠道 Microbiota及其与结肠宿主的相互作用使用新颖的方法和尖端技术，我们的研究具有巨大的翻译潜力，可能导致建立肠道微生物组作为CAC的预测指标 IBD患者的CAC预防和检测方法的风险和辅助方法。