Serum Serotonin Differentiates Between Disease Activity States in Crohn’s Patients

Abstract

Background Diagnosis and monitoring of inflammatory bowel diseases (IBDs) utilize invasive methods including endoscopy and tissue biopsy, with blood tests being less specific for IBDs. Substantial evidence has implicated involvement of the neurohormone serotonin (5-hydroxytryptamine, 5-HT) in the pathophysiology of IBDs. The current study investigated whether serum 5-HT is elevated in patients with active ulcerative colitis (UC) or Crohn’s disease (CD). Methods Serum samples were obtained from a German cohort of 96 CD and UC patients with active disease, refractory disease, or remission of disease based upon their disease activity index (DAI) and disease history. High pressure liquid chromatography with tandemmass spectrometry was used to measure 5-HT, tryptophan (TRP), and kynurenine (KYN) levels in the serum samples, and Luminex Multiplex ELISA was used to measure cytokine levels. Intestinal mucosal biopsies were obtained from a separate cohort of healthy and CD patients, and the immunoreactivity of the serotonin transporter (SERT) was determined. Results There was no statistically significant difference in TRP or KYN levels between disease categories in either UC or CD. Interestingly, 5-HT levels were significantly elevated in patients with active CD but not active UC when compared with the levels in remission or refractory disease. Serum 5-HT was superior to C-reactive protein and circulating cytokines in differentiating between disease categories in CD. Additionally, SERT immunoreactivity was decreased in the ileum and colon of patients with CD compared to healthy controls. Conclusion We have shown that the serum 5-HT can differentiate between active disease and refractory disease or remission among CD patients, emphasizing the potential suitability of serum 5-HT as an auxiliary measure in diagnosing active CD.

TrpNet: Understanding Tryptophan Metabolism across Gut Microbiome

“…Interestingly, although indolepyruvate, which can improve intestinal epithelial barrier function during challenges with inflammatory stimuli, was not annotated by the metabolomics data, our prediction shows its decrease in CD patients, replicating previous results [60]. Despite serotonin being found increased in the CD group by metabolomics analysis, which was possibly due to the decreased expression of SERT in the ileum and colon [62], there was no significant difference according to our prediction. Similarly, the kynurenines were not different between the two groups using all the methods.…”

Disruption of autophagy by increased 5-HT alters gut microbiota and enhances susceptibility to experimental colitis and Crohn’s disease

“…An increase in plasma/serum 5-HT levels is observed in patients with IBD, and the use of selective 5-HT reuptake inhibitors is associated with microscopic colitis ( 21 , 23 , 39 , 40 , 60 , 61 ). In addition, dysfunction in the autophagic process is implicated in the development of intestinal inflammation in patients with IBD ( 5 ).…”

Enteropathogenic infections modulate intestinal serotonin transporter (SERT) function by activating Toll-like receptor 2 (TLR-2) in Crohn’s disease

“…The presence of 5-HT in the GI tract plays a major role in gut motility, neuronal reflexes and fluid secretion. A compelling evidence has suggested that 5-HT is involved in CD pathogenesis, which is characterized by the prevalence of enterochromaffin cells, higher 5-HT mucosal content, increased activity of tryptophan hydroxylase I (TPH-1), and more importantly, lower expression of SERT, a critical regulator of the intestinal 5-HT availability 10 . In the present study, we have confirmed that serum 5-HT level is significantly higher among CD patients in comparison to healthy subjects, and MAP-infected CD patients had a higher level of 5-HT than those without MAP infection.…”

“…These findings support the role of 5-HT 3 receptors in inflammatory and immune responses 8 , 9 . More importantly, a recent clinical study has shown that serum 5-HT is significantly elevated among Crohn’s disease (CD) patients and it can be used to differentiate between active and refractory disease state, which emphasizes on the potential role of 5-HT in diagnosing active CD and its auxiliary indication for disease remission 10 . Likewise, higher levels of 5-HT were found in the intestinal tissue of inflammatory bowel disease (IBD) patients when compared to healthy controls 11 .…”