Diet and Chronic Disease: mechanistic studies on the impact of dietary protein on gut barrier function and the microbiota

项目简介：肠道微生物区系越来越多地与各种慢性疾病联系在一起，包括心血管疾病和肝脏疾病。目前，建议增加膳食蛋白质，但我们还不知道这将对长期健康产生什么影响。一些饮食蛋白质未被消化，最终进入结肠，在那里被一些肠道细菌利用，这可能会扭曲微生物区系。这种改变的微生物群与宿主免疫和新陈代谢的作用不同，不同于不以饮食中过量蛋白质喂养的微生物群。我们之前已经证明，饮食蛋白质的增加可能是“渗漏肠道”综合征发生的一个重要因素，在这种综合征中，肠道屏障没有发挥应有的作用。这意味着来自食物和细菌的各种分子进入血液，并产生低水平的免疫反应。我们还知道，女性和男性的肠道、免疫力、新陈代谢和微生物群非常不同，这表明它们对过量饮食蛋白质的反应可能非常不同。当涉及到开发干预措施以减少肠道渗漏以及随后的慢性病时，这具有重要的意义。本博士将使用仔猪模型更详细地探讨这一问题，并使用尖端微生物区系组成、代谢图谱和免疫学技术确定涉及的机制。

Project Description: The gut microbiota is increasingly being linked to various chronic diseases including cardiovascular and liver disease. Currently, recommendations are to increase dietary protein, but we do not yet know what effect this will have on long term health. Some dietary protein is undigested and ends up in the colon where it is utilized by some gut bacteria and this can skew the microbiota. This altered microbiota interacts with host immunity and metabolism differently to one which is not fed by excess protein in the diet. We have previously shown that increased dietary protein could be an important factor in the development of 'leaky gut' syndrome where the intestinal barrier does not work as it should. This means that various molecules from food and bacteria cross over into the blood stream and generate low-level immune responses. It is this low-grade inflammation which is known to contribute to later chronic disease.We also know that female and male guts, immunity, metabolism and microbiotas are very different which suggests they could respond very differently to excess dietary protein. This has important implications when it comes to the development of interventions to reduce leaky gut and therefore later chronic disease. This PhD will explore this in more detail using a piglet model, and determine the mechanisms involved using cutting-edge microbiota composition, metabolic profiling and immunological technologies.