Characterization of Vitamin D and Serotonin Pathway Variations in Patients with Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder associated with chronic abdominal pain along with recurrent diarrhea, constipation, or both that afflicts millions of people worldwide. Currently, the etiological foundation of the disorder remains enigmatic. However, there is mounting evidence suggesting that serotonin may play a critical role in the pathophysiology of IBS. DNA microarrays analyzing the transcriptomes of 11 IBS patients versus 13 asymptomatic control patients have identified a series of 858 differentially‐expressed genes that may characterize the IBS pathological state. Gene ontology (GO) analysis of this subset of genes revealed that nodes featuring serotonin‐related pathways displayed the highest number of functions relative to other GO groups. Quantitative real‐time polymerase chain reaction (qRT‐PCR) analysis of IBS patient‐derived RNA displayed reduced expression of the rate‐limiting enzyme of the serotonin biosynthetic pathway, tryptophan hydroxylase 1 (TPH1), relative to a pool of RNA comprised of eight control patients. Further, this analysis revealed potential compensatory regulation of several other genes integral to the maintenance of serotonin metabolism. In addition, concentrations of serum 25‐hydroxyvitamin D in both the IBS and control sampled populations indicated a trend towards decreased vitamin D levels within the IBS cohort, regardless of IBS subtype. Finally, vitamin D was shown to be effective in regulating the expression of several key serotonin metabolism genes, alluding to a potential link between vitamin D and serotonin pathways modulating IBS. These findings suggest that the pathogenesis of IBS may be associated with abnormal serotonin metabolism and/or vitamin D deficiency, and provide novel insight into possible treatment regimes. Support or Funding Information Wisconsin Network for Health Research