Isovaleric acid, a specific metabolite in stools from CRC patients, promotes the expression of tryptophan hydroxylase 2 (Tph2) and 5-HT production in intestinal 5-HT+ neurons, and 5-HT in turn promotes the self-renewal of ISCs, demonstrating a metabolite–neuron–CSC axis [122]. Here, TPH2 is linked to colorectal carcinoma.