Coffee induces AHR- and Nrf2-mediated transcription in intestinal epithelial cells

Toydemir, Gamze; Loonen, Linda M.P.; Venkatasubramanian, Prashanna Balaji; Mes, Jurriaan J.; Wells, Jerry M.; Wit, Nicole de


Coffee induces a health-promoting adaptive response of cells in the body. Here, we investigated enterocyte responses to AHR agonists in coffee and measured their transport across a polarized intestinal epithelium. AHR-activating potencies of Turkish, filter, and instant coffee were determined using DR CALUX® bioassay, before and after intestinal metabolization by Caco-2 cells. Furthermore, effects of coffee on induction of AHR- and Nrf2-pathway genes in Caco-2 cells were evaluated by real-time qPCR. Coffee samples showed considerable AHR-activating potencies in DR CALUX® bioassay (up to 79% of positive control activity). After incubation with Caco-2 cells, AHR activity of different coffees was between 35 and 64% of their initial value, suggesting rapid uptake and metabolization by epithelial cells. Expression of AHR-regulated gene CYP1A1 increased up to 41-fold and most Nrf2-pathway genes were up-regulated by coffee. This in vitro study may support the notion that coffee bioactives contribute to antioxidant defense and detoxification processes in vivo.