Serotonin transporter and cholecystokinin in diarrhea-predominant irritable bowel syndrome: Associations with abdominal pain, visceral hypersensitivity and psychological performance

Background: Visceral hypersensitivity and psychological performance are the main pathophysiological mechanisms of irritable bowel syndrome (IBS). Previous studies have found that cholecystokinin (CCK) can enhance colon movement and that serotonin transporter (SERT) is a transmembrane transport protein with high affinity for 5-hydroxytryptamine, which can rapidly reuptake 5-hydroxytryptamine and then regulate its action time and intensity. We speculate that SERT and CCK might play a role in the pathogenesis of diarrhea-predominant IBS (IBS-D) by affecting visceral sensitivity and the brain-gut axis.

Aim: To determine SERT and CCK levels in IBS-D patients diagnosed using Rome IV criteria and to analyze their associations with abdominal pain, visceral hypersensitivity and psychological performance.

Methods: This study collected data from 40 patients with IBS-D at the China-Japan Friendship Hospital from September 2017 to April 2018 and 18 healthy controls. The severity of abdominal pain, visceral sensitivity and psychological performance were evaluated in IBS-D patients and healthy controls, the levels of SERT and CCK in plasma and colonic mucosa were evaluated, and the correlations between them were analyzed.

Results: There were significant differences in the initial sensation threshold (31.00 ± 8.41 mL vs 52.22 ± 8.09 mL, P < 0.001), defecating sensation threshold (51.75 ± 13.57 mL vs 89.44 ± 8.73 mL, P < 0.001) and maximum tolerable threshold (97.25 ± 23.64 mL vs 171.11 ± 20.83 mL, P < 0.001) between the two groups. IBS-D patients had more severe anxiety (7.78 ± 2.62 vs 2.89 ± 1.02, P < 0.001) and depressive (6.38 ± 2.43 vs 2.06 ± 0.73, P < 0.001) symptoms than healthy controls. Significant differences were also found in mucosal CCK (2.29 ± 0.30 vs 1.66 ± 0.17, P < 0.001) and SERT (1.90 ± 0.51 vs 3.03 ± 0.23, P < 0.001) between the two groups. There was a significant positive correlation between pain scores and mucosal CCK (r = 0.96, 0.93, 0.94, P < 0.001). Significant negative correlations between anxiety (r = -0.98; P < 0.001), depression (r = -0.99; P < 0.001), pain evaluation (r = -0.96, -0.93, -0.95, P < 0.001) and mucosal SERT were observed.

Conclusion: IBS-D patients had psychosomatic disorders and visceral hypersensitivity. SERT and CCK might be involved in the pathogenesis of IBS-D by regulating the brain-gut axis and affecting visceral sensitivity. This provides a new potential method for identifying a more specific and effective therapeutic target.

Keywords: Abdominal pain; Cholecystokinin; Irritable bowel syndrome; Psychological performance; Serotonin transporter; Visceral hypersensitivity.