Observational Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. May 6, 2020; 8(9): 1632-1641
Published online May 6, 2020. doi: 10.12998/wjcc.v8.i9.1632
Serotonin transporter and cholecystokinin in diarrhea-predominant irritable bowel syndrome: Associations with abdominal pain, visceral hypersensitivity and psychological performance
Geng Qin, Yu Zhang, Shu-Kun Yao
Geng Qin, Yu Zhang, Graduate School, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
Geng Qin, Shu-Kun Yao, Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
Author contributions: Qin G performed the study, analyzed the data and drafted the manuscript; Zhang Y contributed to the performance of the study and revised the manuscript; Yao SK designed the study, revised the manuscript, supervised the study performance and obtained the funding.
Supported by the National Key Technology Support Program during “12th Five-Year Plan” period of China, No. 2014BAI08B00; and the Leap-forward Development Program for Beijing Biopharmaceutical Industry (G20), No. Z171100001717008.
Institutional review board statement: This study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of China-Japan Friendship Hospital.
Informed consent statement: All subjects were informed of the study details and provided written informed consent.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: No additional data are available.
STROBE statement: The manuscript was revised according to the STROBE statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Shu-Kun Yao, MD, PhD, Professor, Department of Gastroenterology, China-Japan Friendship Hospital, 2nd Yinghua East Road, Chaoyang District, Beijing 100029, China. shukunyao@126.com
Received: December 28, 2019
Peer-review started: December 28, 2019
First decision: January 11, 2020
Revised: January 21, 2020
Accepted: April 4, 2020
Article in press: April 4, 2020
Published online: May 6, 2020
Abstract
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: Irritable bowel syndrome, Abdominal pain, Visceral hypersensitivity, Psychological performance, Serotonin transporter, Cholecystokinin

Core tip: This study comprehensively evaluated the symptoms, mental state and visceral sensitivity of patients with diarrhea-predominant irritable bowel syndrome (IBS-D), and further determined serotonin transporter (SERT) and cholecystokinin (CCK) levels in IBS-D patients diagnosed using Rome IV criteria and analyzed their associations with abdominal pain, visceral hypersensitivity and psychological performance. The results showed that the expression of CCK was positively correlated with abdominal pain, while the expression of SERT was negatively correlated with abdominal pain, anxiety and depression, which revealed that SERT and CCK might be involved in the pathogenesis of IBS-D and may provide a new potential method for identifying a more specific and effective therapeutic target.