Serum Serotonin/Tryptophan Ratio Correlates with Inflammation in Crohn's Disease Patients

Abstract

Inflammatory bowel diseases (IBD), which primarily consist of ulcerative colitis and Crohn's disease (CD) are characterized by persistent inflammation of the gastrointestinal (GI) tract. The current standard for diagnosis of IBD utilizes invasive methods including endoscopy and tissue biopsy, with blood tests being less specific for IBD. Substantial evidence has implicated involvement of the neurohormone serotonin (5‐hydroxytryptamine, 5‐HT) in the pathophysiology of IBD. Both mRNA and protein levels of serotonin transporter (SERT) have been consistently shown to be decreased in the intestinal mucosa of IBD patients. However, there is disagreement between previous studies on whether mucosal 5‐HT is increased or decreased in IBD. Furthermore, serum levels, rather than tissue levels, of 5‐HT in patients with IBD have not yet been examined. The current study examined 5‐HT, tryptophan (TRP), and kynurenine (KYN) levels in CD patients to test the hypothesis that 5‐HT serum levels correlate with inflammation.MethodsSerum samples were obtained from a German cohort of 45 CD patients and were categorized into one of three groups based upon their CD activity index (CDAI) and disease history. 15 patients were in remission (CDAI < 150), 15 patients had active disease (CDAI > 450), and 15 patients had chronic disease characterized by persistence of clinical symptoms and no lasting remission after adequate drug therapy. Age, gender, and race were not significantly different between the three groups. LC‐MS was used to measure 5‐HT, TRP, and KYN levels in the serum samples and Luminex Multiplex ELISA was used to measure cytokine levels. Results are shown as 95% confidence intervals of the mean.ResultsTRP and its derivatives 5‐HT and KYN were measured in CD patient serum: 5‐HT (0.65 – 0.93 μM), TRP (50.93 – 59.67 μM), and KYN (1.94 – 2.55 μM). To normalize for differences in body TRP levels, data were calculated as a ratio between 5‐HT and TRP (5‐HT/TRP) and between KYN and TRP (KYN/TRP). There were no significant differences in 5‐HT, TRP, and KYN levels between remission, active, and chronic groups. However, the 5‐HT/TRP ratio was significantly elevated in CD patients with active disease (0.014 – 0.034, p < 0.01) as compared either to patients in remission (0.009 – 0.017) or with chronic disease (0.009 – 0.018) with no difference in KYN/TRP ratio. Further, the 5‐HT/TRP ratio positively correlated with serum C‐reactive protein levels (r = 0.47, p < 0.01), serum IL‐1β levels (r = 0.52, p < 0.01), and serum TNF‐α (r = 0.36, p < 0.05). In conclusion, we have shown that the serum 5‐HT/TRP ratio can discriminate between active disease and chronic disease or remission among CD patients. In addition, the 5‐HT/TRP ratio correlates with established serum markers of inflammation in CD patients, emphasizing the important role that 5‐HT plays in the pathophysiology of IBD.Support or Funding InformationNIDDK NIH R01 DK098170, NIDDK NIH F30 DK113703This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.