DETERMINING THE INTERRELATIONSHIPS FOR DIETARY INTAKE OF LIPID OXIDATION PRODUCTS FROM THERMALLY ABUSED OILS, THE GUT MICROBIOME, AND GUT HEALTH

Thermal processing of vegetable oils high in unsaturated fatty acids generates lipid oxidation products (LOPs) that can adversely affect human health. The consumption of fried foods represents a significant route of exposure to these toxic compounds. However, the impact of dietary intake of LOPs from thermally abused oils (TAOs) on the gut microbiome and the associated effects on gut health remain largely unexplored. Our overarching objective is to investigate the interrelationships for dietary intake of LOPs from TAOs, the gut microbiome, and gut health. Our specific objectives are: 1) Determine the impacts of acute, subchronic, or chronic exposure to dietary TAOs on biomarkers of gut inflammation, the composition of the gut microbiome, and underlying molecular pathways mediating mucosal inflammatory and immune response in healthy C57BL6/J mice. 2) Determine the role of chronic exposure to dietary TAOs in modulating symptoms of colitis and progression to colon tumorigenesis, shifting the composition of the gut microbiome, and altering mucosal immune and inflammation pathways using the AOM/DSS model of colitis-associated colorectal carcinogenesis. 3) Determine the direct relationship of dietary TAOs on intestinal epithelial cells and the gut microbiome using in vitro cell culture and batch fermentation methods. The findings will provide valuable insights into the relationship between the dietary intake of TAOs and the composition and metabolic function of the gut microbiome in healthy mice and a mouse model of colitis-associated colorectal cancer.Milestones and TimelineYear 1: Diet preparation, Perform Experiment 1Year 2: Experiment 1 sample processing; Experiment 2 analysis; Experiment 2 diet preparation; perform Experiment 2; manuscript preparation.Year 3: Experiment 2 sample processing; Experiment 2 analysis; Experiment 3 (complete); manuscript preparation.Year 4: Experiments 4 and 5 (complete); manuscript preparation.