Bile acid modification by the human gut microbiota and its role in pathogenesis of colorectal cancer

人类肠道微生物群对胆汁酸的修饰及其在结直肠癌发病机制中的作用

• 批准号: G0901553/1
• 负责人: Brian Jones
• 金额: $ 51.45万
• 依托单位: University of Brighton
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0901553%2F1
• 关键词: Bile; acid; modification; human; gut

The human gut is home to a wide range of bacteria, and every adult harbours around 100 trillion microbial cells in their intestines belonging to hundreds of bacterial species. This population of bacteria is referred to as the gut microbiota, and these bacteria are thought to undertake numerous beneficial activities. However some of the activities undertaken by the gut microbiota may be involved in the development of colorectal cancer (CRC). Diet, and in particular a high intake of animal fat and red meat, has been identified as a major risk factor for CRC, but it is not yet clear how these dietary factors lead to the development of CRC. It is important for us to understand the causes of diseases like CRC, in order to develop effective treatments or identify ways in which the disease could be prevented altogether.Recent studies have indicated that the gut microbiota may be an important factor in the influence of diet on CRC risk, and in particular the ability of gut microbes to modify components of bile, called bile acids. Bile acids are naturally produced by our bodies to help us digest the fat contained within the food we eat, and a diet rich in fat results in a increased level of bile acid in the intestine. Bile acids are readily converted to different forms by the gut microbiota, and some of these altered bile acids may be carcinogenic and affect the expression of genes thought to be important in the development of CRC.The purpose of this study is to investigate the relationship between the modification of bile acids by gut bacteria and development of CRC, to determine how these microbes may cause this disease. By comparing the gut bacteria of individuals with CRC and those who are healthy, we will be able to identify any association between activities of these microbes and risk of disease. Subsequently we will be able to look at the effect of these bacteria on specific human genes known to be associated with CRC, which will allow us to identify the how gut bacteria may trigger development of CRC.

人类肠道是各种细菌的家园，每个成年人的肠道中都有大约100万亿个微生物细胞，属于数百种细菌。这种细菌群体被称为肠道微生物群，这些细菌被认为具有许多有益的活动。然而，肠道微生物群进行的一些活动可能参与结直肠癌（CRC）的发展。饮食，特别是大量摄入动物脂肪和红肉，已被确定为CRC的主要风险因素，但尚不清楚这些饮食因素如何导致CRC的发展。了解结直肠癌等疾病的病因，对于开发有效的治疗方法或确定完全预防该疾病的方法非常重要。最近的研究表明，肠道微生物群可能是饮食影响结直肠癌风险的重要因素，特别是肠道微生物改变胆汁成分（称为胆汁酸）的能力。胆汁酸是由我们的身体自然产生的，以帮助我们消化我们吃的食物中含有的脂肪，富含脂肪的饮食会导致肠道中胆汁酸水平的增加。胆汁酸很容易被肠道菌群转化为不同的形式，其中一些改变的胆汁酸可能是致癌的，并影响被认为是重要的基因的表达在CRC的发展。本研究的目的是调查肠道细菌和CRC的发展之间的关系，胆汁酸的修饰，以确定这些微生物如何可能导致这种疾病。通过比较CRC患者和健康人的肠道细菌，我们将能够确定这些微生物的活动与疾病风险之间的任何关联。随后，我们将能够研究这些细菌对已知与CRC相关的特定人类基因的影响，这将使我们能够确定肠道细菌如何引发CRC的发展。