Gut microbiota breakdown indigestible food rests in the proximal colon to produce short chain fatty acids, one of which is butyrate. Butyrate is the main source of energy for the colonocytes. Butyrate must enter the colonocyte through specific transporters located on the luminal side of the colonic mucosa. Two main transport systems are described: (i) the electroneutral H+- coupled monocarboxylate transport (MCT) of which SLC16A is the major one and (ii) the electrogenic Na+ – coupled monocarboxylate transport (SMCT) of which SLC5A8 is the main transporter. Evidence suggests butyrate concentration is reduced in certain gastrointestinal conditions affecting the colon. Butyrate transporters are also regulated up- or downwards depending on butyrate concentration in the colon. Using gas chromatography mass spectroscopy (GC-MS), we have studied the presence of butyrate in patients with irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) and colorectal cancer (CRC). IBS is a functional bowel disorder associated with changed bowel habit, abdominal pain, bloating and flatulence. Two main types are distinguished: a constipation predominant type (C-IBS) and a diarrhoea predominant type (D-IBS). In IBD there is idiopathic inflammation and ulceration of the colon with symptoms of bloody diarrhoea, abdominal cramping and weight loss. Crohn’s disease (CD) and ulcerative colitis (UC) are the two main entities. IBD predisposes to CRC. CRC is the fourth most prevalent cancer worldwide associated with significant morbidity, mortality and healthcare cost. Butyrate has been shown to be reduced in IBD and CRC, but not significantly in IBS. Furthermore, we studied the expression of the butyrate transporters, SLC16A and SLA5A8 in the same patient groups. The data showed that mRNA expression of both transporters was expression of both transporters was significantly reduced in all disease states, except for CD. Therefore, the presence of butyrate in the colon is important for colonocyte function. However, this alone is not sufficient, as the important factor is the transfer of available butyrate into the cell. This data showed that butyrate transporters are down regulated in all disease groups suggesting that available butyrate does not get into the cell. Thus, butyrate supplementation will be an ineffective form of therapy. This hypothesis was proven in studies of human subjects with UC treated with butyrate. Instead, a way of stimulating the butyrate transporters will be a far more effective therapeutic strategy.