Our study suggests that, in a controlled, in vitro model, the active metabolite of vitamin D is capable of reversing potentially aberrant/pathological IBS gene expression with emphasis on serotonergic metabolism given the GO analysis highlighting serotonergic signaling and the markedly significant increase in SERT and TPH1 expression in HCT-116 colorectal cells when treated with 1,25D. Here, SLC6A4 is linked to irritable bowel syndrome.