Polyphenols and Tryptophan Metabolites Activate the Aryl Hydrocarbon Receptor in an in vitro Model of Colonic Fermentation

Abstract

Scope Many dietary phytochemicals have been reported to promote gut health. Specific dietary phytochemicals, such as luteolin, as well as specific microbial metabolites of tryptophan are ligands of the aryl hydrocarbon receptor (AhR), which plays a role in immunity and homeostasis of the gut barrier. Here, the fate of luteolin during colonic fermentation and the contribution of tryptophan metabolites to AhR activity in different parts of the colon are investigated. Methods and results Several polyphenols are screened for AhR activation and oregano, containing the ligand luteolin, is added to batch cultures of human microbiota from the distal colon. Luteolin is rapidly metabolized, with no measurable increase in AhR activity. In the second experiment, using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME), not all luteolin is metabolized in the ascending colon, but disappear rapidly in the transverse colon. The greatest AhR activity is due to microbiota‐derived metabolites of tryptophan, particularly in the descending colon. Conclusions Luteolin in food is rapidly metabolized in the transverse colon. Tryptophan metabolism by the microbiota in the colon contributes substantially to the pool of lumen metabolites that can activate the AhR.

Aryl hydrocarbon Receptor activation during in vitro and in vivo digestion of raw and cooked broccoli (brassica oleracea var. Italica)

“…49 However, their concentrations were too low to trigger a significant AhR activation in our reporter assay. 50 Overall, the data from the ileostomy study indicate that the concentration of indole derivatives arriving in the ileum level after broccoli soup consumption was too low to produce a significant increase in the AhR activation with the in vitro assay used herein. This may be due to a limited formation of AhR ligands from glucobrassicin or their absorption through the small intestinal epithelium.…”

“…We have previously measured the activation induced by quercetin, a flavonoids relatively abundant in broccoli in our previous study and could not find a significant activation from it. 50…”

Dietary natural flavonoids treating cancer by targeting aryl hydrocarbon receptor

“…In addition, Gates et al studied the relationship between the intake of five common dietary flavonoids and the incidence of ovarian cancer in an earlier prospective study review. These five flavonoids include myricetin, kaempferol, quercetin, luteolin, and apigenin (Gates et al 2007;Koper et al 2019). Unfortunately, there was no clear correlation between the total intake of the five flavonoids examined and the incidence of ovarian cancer (Kawai 2018).…”

Models of the Gut for Analyzing the Impact of Food and Drugs

“…The SHIME simulator has been adopted in a recent study on the metabolism of different polyphenols and oregano‐derived luteolin known to be a ligand of the aryl hydrocarbon receptor (AhR), which plays a role in improving gut barrier functions and the intestinal immune defense. In this study, the authors could determine which, among the selected AhR agonists, provide the higher activation of the receptor, with specific attention to the evolution of the fermentation in the different sections of the SHIME . Importantly, when studying microbiota in vitro, one should distinguish between luminal and mucosal microbiota.…”

“…Examples of Macromodels of the human gut. A) A photograph of the SHIME model developed by ProDigest and adopted at Wageningen University . B) The SIMGI gastrointestinal in vitro model 128b,129.…”