Exploring the molecular consequences of processed food intake

Background: Advanced glycation endproducts (AGEs), formed via the processing of foods, are a major constituent of our modern convenience diet. Environmental factors, including over-nutrition and excess dietary intake of AGEs are suggested to contribute to the progression of chronic diseases, including diabetes and chronic kidney disease (Coughlan et al., Diabetes 2011) and studies from our laboratory indicate that dietary AGEs affect the gut (Snelson et al., Science Advances 2021). Microbial cells make up the majority of cells in the human body, and most of these reside in the intestinal tract. Researchers have long recognized that some intestinal microorganisms are associated with health, but the beneficial impact of most of the gut’s microbes on human metabolism has been discovered only relatively recently (de Vos & de Vos, J Nutr Reviews 2012). Emerging evidence suggests that bacterial dysbiosis within the colon may be implicated in the pathogenesis of the metabolic syndrome, type 2 diabetes and cardiovascular disease. Supplementation of the diet with prebiotics promote the selective proliferation of beneficial microbial species. How dietary AGEs specifically influence gut microbial ecology and disrupt gut barrier function is not known. Research question: Does a high AGE diet influence gut barrier integrity, leading to disease? Aim: The aim of this study is to investigate the effects of excess consumption of dietary AGEs on gut barrier function and the progression of chronic kidney disease in a mouse model, with or without prebiotic supplementation. Project related methods/skills/technologies: • Dietary intervention studies. • Mouse metabolic phenotyping and body composition. • Western immunobloting and ELISA. • Fluorogenic and colorimetric enzyme activity assays using scanning plate reader. • Assessment of renal and gut morphometry to determine pathology. • Metabolomics This project is available as an Honours or a PhD project and would be suitable for a student with a strong interest in nutrition.