Substrate-Driven Differences in Tryptophan Catabolism by Gut Microbiota and Aryl Hydrocarbon Receptor Activation

Huang, Zhan; Schoones, Tessa; Wells, Jerry M.; Fogliano, Vincenzo; Capuano, Edoardo


Scope: This study aims to investigate the effect of tryptophan sources on tryptophan catabolism by gut microbiota and the aryl hydrocarbon receptor (AhR) activation. Methods and Results: Four substrates (free tryptophan, soybean protein, single and clustered soybean cells) containing an equimolar amount of tryptophan, but with a different bioaccessibility are studied using in vitro batch fermentation. Tryptophan catabolites are identified by LC-MS/MS. AhR activity is measured by HepG2-Lucia AhR reporter cells. The total amount of tryptophan-derived catabolites increases with decreasing level of substrate complexity. Indole is the major catabolite produced from tryptophan and it is the most abundant in the free tryptophan fermentation. Indole-3-acetic acid and indole-3-aldehyde are abundantly generated in the soybean protein fermentation. The soybean cell fermentation produced high concentrations of tryptamine. Interestingly, large amounts of short-chain fatty acids (SCFAs) are also found in the soybean cell and protein fermentation. Both tryptophan-derived catabolites and SCFAs are able to increase AhR reporter activity over time in all four groups. Conclusion: This study illustrates that bacterial catabolism of tryptophan and resulting AhR activation in the gut is modulated by the food matrix, suggesting a role for food design to improve gut health.