We will discuss here how serotonin forms and its role on gut motility, the factors that can fluctuate the level of serotonin in the gut, how SERT maintains serotonin level in the gut, which factors affect SERT transcription, and lastly treatment of IBS targeted on 5HT receptors and serotonin reuptake mechanism. Here, SLC6A4 is linked to irritable bowel syndrome.