BROCCOLI-MEDIATES FUNCTIONAL CHANGES IN THE GUT MICROBIOME

Cruciferous vegetables e.g. broccoli and brussel sprouts are an important component of a healthy diet. Consumption of these vegetables correlates with a decreased incidence of various cancers. There are a number of chemical components (e.g. isothiocyanates and soluble fibre) in such vegetables that have been demonstrated to exhibit significant effects upon mammalian cellular processes. Perhaps the most studied constituent of cruciferous vegetables is the breakdown product of indole glucosinolate, namely indole-3-carbinol, which forms indolo[3,2b] carbazole (ICZ) in the stomach. The relevance of ICZ to intestinal homeostasis has been largely overlooked and is the focus of this application. ICZ has been demonstrated to be a high-affinity activator for the Aryl hydrocarbon receptor (AHR) with the capacity to induce AHR-mediated biological activity. We will address the hypothesis that broccoli can functionally alter the gut microbiota (bacteria in the gut) and that such alteration is dependent upon activation of the AHR. Furthermore, we will examine whether these changes in the gut bacteria will decrease intestinal inflammation. Genetically modified mouse models (mice that lack AHR expression) will be used to test whether the positive effects of dietary broccoli consumption are mediated through activation of the AHR. For example, if indeed it turns out that activation of the AHR by broccoli consumption improves gut health, this information will be of value to growers to grow specific varieties of broccoli that have relatively high amounts of the chemical that leads to AHR activation. In addition, this work will allow nutritionist to decide whether they should recommend an increased level of cruciferous vegetable consumption.