D-amino acids as modulators of the genotoxic polyketide, colibactin.

D-氨基酸作为基因毒性聚酮化合物大肠杆菌素的调节剂。

• 批准号: BB/W015781/1
• 负责人: Andrew Roe
• 金额: $ 61.11万
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FW015781%2F1
• 关键词: amino; acids; modulators; genotoxic; polyketide

"You are what you eat" is a commonly used phrase that everyone should take on board. For example, information from over 4 million patients has shown that obesity, type 2 diabetes, and poor metabolic health are three significant risk factors for worse COVID-19 outcomes. These risk factors are heavily influenced by the food we eat. The challenge is that our diet is complex and it can be hard to know what is "good" or "bad" for you. Moreover, there is an increasing appreciation of the importance of our "gut health", the complex mix of different microbes that help us break down food and protect against harmful bacteria. Many people try and supplement their gut microbes with so called "good bacteria" or probiotics that claim to provide, and in some cases are even shown, to have clear positive impacts. But do we know these probiotics are actually safe? Recent work has shown that strains of E. coli that have been used for almost 100 years as probiotics, can actually produce a toxin that induces colo-rectal cancer. This is really worrying for us. For example, bowel cancer is the 3rd most common cancer (10% of all new female cancer cases/ 13% of all new male cancer cases) in the UK and highly related to diet. By chance, we have found a simple supplement that helps reduce the production of the toxin made by E. coli when it is grown in the lab. We now have 3 important questions: (1) can we make even more effective supplements to block the toxin. (2) how does the supplement affect toxin production and (3) can it work in animals? These are the three aims of this work. In addition, our work also aims to understand if the supplement itself affects the normal bacteria within the gut. We will test this by looking at the different species that live in the gut before and after the treatment. This is key to knowing that the treatment itself does not cause problems.

“你吃什么就是什么”是每个人都应该接受的常用短语。例如，来自400多万患者的信息表明，肥胖、2型糖尿病和代谢健康状况差是导致COVID-19结果恶化的三个重要风险因素。这些风险因素受到我们所吃食物的严重影响。挑战在于我们的饮食是复杂的，很难知道什么对你来说是“好”或“坏”的。此外，人们越来越认识到我们的“肠道健康”的重要性，不同微生物的复杂混合有助于我们分解食物并防止有害细菌。许多人尝试用所谓的“好细菌”或益生菌补充他们的肠道微生物，这些益生菌声称提供，在某些情况下甚至显示出明显的积极影响。但是我们知道这些益生菌真的安全吗？最近的研究表明，E.大肠杆菌作为益生菌已经使用了近100年，实际上可以产生一种毒素，导致结肠直肠癌。这确实令我们担忧。例如，肠癌是英国第三大最常见的癌症（占所有新发女性癌症病例的10%/所有新发男性癌症病例的13%），并且与饮食高度相关。一次偶然的机会，我们发现了一种简单的补充剂，可以帮助减少大肠杆菌毒素的产生。在实验室中培养的大肠杆菌。我们现在有3个重要的问题：（1）我们可以做更有效的补充，以阻止毒素。(2)补充剂如何影响毒素的产生和（3）它能在动物中起作用吗？这就是这项工作的三个目标。此外，我们的工作还旨在了解补充剂本身是否会影响肠道内的正常细菌。我们将通过观察治疗前后肠道中的不同物种来测试这一点。这是了解治疗本身不会引起问题的关键。