Tryptophan and the innate intestinal immunity: Crosstalk between metabolites, host innate immune cells, and microbiota

The intestinal mucosal barrier is critical for the absorption of nutrients and the health of both humans and animals. Recent publications from clinical and experimental studies have shown the importance of the nutrients-bacteria-host interaction for the intestinal homeostasis. Dysfunction of these interactions has been reported to be associated with metabolic disorders and development of intestinal diseases such as the irritable bowel syndrome and inflammatory bowel diseases. Tryptophan and its metabolites, including kynurenine, kynurenic acid, and 5-hydroxytrptamine, can influence the proliferation of enterocytes, intestinal integrity, and immune response, as well as intestinal microbiota, therefore, regulating and contributing to the intestinal health. In this review, we highlight recent findings on the effect of tryptophan and its metabolites on the mucosal barrier and intestinal homeostasis and its regulation of innate immune response. Moreover, we present the signaling pathways related to Trp metabolism, such as mammalian target of rapamycin, aryl hydrocarbon receptor, and pregnane X receptor, which contribute to the intestinal homeostasis and discuss future perspectives on spontaneous interference in host tryptophan metabolism as potential clinical strategies of intestinal diseases.