IDENTIFICATION OF DIETARY PHYTOCHEMICALS TO MODULATE CHRONIC GI DISEASES

This project is focused on the examination of diverse, phytochemical-rich foods (mushrooms, peppers, carrots, and berries) to discover their effects on modulating AHR activation, as well as elucidating the chemical agents responsible for this activity. Furthermore, we will ascretain the phytochemicals'interaction with the gut microbiome, and probe their downstream effects on gastrointestinal inflammation and disease. We will achieve this via the following objectives:Objective 1:To efficiently identify AHR-active ligands from complex dietary matrices (e.g., peppers, mushrooms, carrots, berries) and analyze structural features of active compounds that are effective in modulating AHR activity.1.1.Identify putative AHR ligands from botanical foods for in vitro AHR activation.1.2. Use chemo-informatics to identify characteristics of AHR active molecules that optimize functionality.Objective 2:To categorize AHR ligand metabolism by gut microbiome and their in vivo effect on gut homeostasis and cell development.2.1.In vivo assessment of AHR activation of each botanical food.2.2.Comparative metabolomics analysis to identify microbiome-generated metabolites and determine interactions with the gut microbiome.Objective 3:To assess protective mechanisms of dietary AHR ligands against intestinal injury and inflammation in an inflammatory bowel syndrome (IBS) model.3.1.Identification and binding activity of microbial AHR-active compoundsusing a photoaffinity ligand binding assay.3.1.Examine effect of AHR ligands on modulating chemically induced intestinal injury in an in vivo mouse model.