Abstract
Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation and its treatment varies widely; however, when inflammation is high, a complete nutrient containing pre-digested elemental diet (ED) is used to preserve the intestinal tract. In this study, we investigated the mechanisms underlying the effectiveness of EDs for IBD using mice. C57BL/6 mice were orally treated with the ED (5 mL/day) and its ingredient L-tryptophan (Trp) (1-100 mg/kg), respectively. Flow cytometry analysis revealed that treatment with the ED and Trp (10 and 100 mg/kg) significantly increased the percentage of splenic CD4+-/CD25+-/Foxp3+ regulatory T cells (Tregs). In the 2% DSS-induced colitis-mouse model, Trp administration (100 mg/kg) led to a significant decrease in TNF-α and increase in IL-10 in the serum as well as a significant decrease in the inflammation score. Furthermore, the aryl hydrocarbon receptor (AhR) agonistic activity, which is a key function of Treg induction, of Trp and 15 Trp metabolites was characterized using a highly sensitive DR-EcoScreen cell assay. Five Trp metabolites, including L-kynurenine, acted as AhR agonists, while Trp did not. Taken together, these results suggest that the ED treatment has a Trp-dependent immunoregulatory effect, and several Trp metabolites that activate the AhR might contribute to induction of remission in patients with IBD.