Consistently, in the current study, the elevated expression of IDO1 induced by CRS facilitated the conversion of the Trp signaling to the toxic Kyn pathway, contributing to Kyn, 3-HK, and Quin accumulation in colon, which may aggravate gut integrity impairment, and increase periphery Kyn and other toxic metabolites, serving as an accomplice of depression. This evidence concerns the gene IDO1 and major depressive disorder.