Mechanistic studies on the impact of dietary protein on gut barrier function: a gatekeeper of metabolic & immune health

肠道屏障起到防止细菌和细菌产物进入全身血液循环的作用。如果肠道屏障失效，细菌产品可以渗透到身体组织，导致新陈代谢和免疫功能障碍。这种效应的最好例子发生在导致细菌脂多糖(LPS)从肠道转移到肝脏的炎症条件下，在这种情况下，LPS被认为促进了异位脂肪和非酒精性脂肪性肝病的积聚，这是一种导致心血管疾病和终末性肝病发展的常见疾病。我们有新的证据表明，以肠道通透性增加来衡量的肠道屏障功能在健康男性中也受到了损害，这种现象被称为“肠道渗漏”。虽然这种情况的病因学可能是多因素的，但有新的证据表明，饮食蛋白质的发酵产物可能会损害结肠的肠道屏障功能，特别是在缺乏可发酵碳水化合物的情况下。如果这种联系能够得到证实，它将对英国人口中蛋白质的过度消费产生重大影响，特别是在建议的中年成年人增加蛋白质摄入量的饮食建议方面。我们的研究计划旨在利用萨里大学(UoS)和雷丁大学(UOR)合作项目的体外和人类干预研究，确定肠道通透性、饮食蛋白质和免疫和代谢健康之间的关系。来自不同食物来源(牛肉、牛奶、鸡蛋、大豆、豌豆)的蛋白质发酵产品将在反映人类结肠的体外消化系统中进行检测。通过进行饮食干预研究，将检查产生丁酸最少的蛋白质来源对人体肠道通透性、微生物区系和新陈代谢健康的影响。这些研究的目的将是为饮食蛋白质和肠道屏障功能受损之间的因果联系提供独特的证据，并对肠道微生物区系的作用和这种影响的不利代谢分支提供新的机械性见解。假设1：饮食蛋白质将增加

The gut barrier functions to prevent the passage of bacteria and bacterial products into the systemic blood circulation. If the gut barrier fails, bacterial products can infiltrate bodily tissues, causing metabolic and immune dysfunction. The best example of this effect occurs in inflammatory conditions that lead to a translocation of bacterial lipopolysaccharide (LPS) from the gut to the liver, where LPS has been implicated in promoting the accumulation of ectopic fat and non-alcoholic fatty liver disease, a common condition that contributes to the development of cardiovascular and terminal liver diseases. We have new evidence to show that gut barrier function, as measured by an increase in gut permeability, is also impaired in healthy men, a phenomenon known as 'leaky gut'. While the aetiology of this condition is likely to me multifactorial, there is emerging evidence to suggest that the fermentation products of dietary protein may impair gut barrier function in the colon, especially in the absence of fermentable carbohydrate. If this link can be substantiated, it would have major implications for the over consumption of protein in the UK population, especially with respect to proposed dietary recommendations to increase protein intake in middle-aged adults. Our research proposal aims to determine the relationship between gut permeability, diet protein and immune and metabolic health using in vitro and human intervention studies in a collaborative project between the Universities of Surrey (UoS) and Reading (UoR). The profile of protein fermentation products from different food sources (beef, milk, egg, soy, pea) will be examined in in vitro digestion systems that reflect the human colon. The protein source that produces the least butyrate will be examined for its impact on gut permeability, the microbiota and metabolic health in humans by undertaking a dietary intervention study. The aims of these studies will be to provide unique evidence for a causal link between dietary protein and impaired gut barrier function, and new mechanistic insights into the role of the gut microbiota, and adverse metabolic ramifications of this effect.Hypothesis 1: Increased dietary protein will result