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

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