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
ARTICLE HIGHLIGHTS
Research background

Diarrhea-predominant irritable bowel syndrome (IBS-D) patients have psychosomatic disorders and visceral hypersensitivity. Preclinical studies have shown that the expression of serotonin transporter (SERT) in the gut can affect the mental and psychological symptoms of IBS patients. Patients with lower expression of SERT are more likely to have negative emotions (somatization, anxiety, depression, hostility). An injection of cholecystokinin (CCK) can enhance and induce colonic motility, resulting in abdominal pain. Few studies have reported the relationship between mucous SERT, CCK levels and symptom severity, anxiety, depression and visceral hypersensitivity in patients. It has been suggested that SERT and CCK may be involved in the pathogenesis of IBS-D.

Research motivation

The present research includes three aspects: (1) General demographic characteristics, symptoms, psychological factors and visceral sensitivity; (2) The expression of SERT and CCK in colonic mucosa of IBS-D patients; and (3) Correlations between CCK, SERT and other parameters. Similar to preclinical studies in IBS-D patients, SERT and CCK may be involved in the pathogenesis of IBS-D, which provides a new potential method for identifying a more specific and effective therapeutic target.

Research objectives

The purpose of this study was to determine the expression of SERT and CCK in colonic mucosa of IBS-D patients, and analyze the relationship between SERT, CCK and general demographic characteristics, symptoms, psychological factors and visceral hypersensitivity.

Research methods

The participants were evaluated by questionnaires (IBS symptom severity scale, visceral sensitivity index, hospital anxiety and Depression Scale) to obtain clinical and psychological characteristics, and underwent colonoscopy and mucosal biopsies. Visceral sensitivity was detected by a high-resolution manometric system, and the expression of SERT and CCK were detected by immunohistochemistry. Mucosal SERT and CCK mRNA levels were measured by real-time quantitative PCR. These parameters were statistically analyzed using SPSS version 24.0.

Research results

The results showed that the anxiety and depression symptoms and visceral sensitivity in IBS-D patients were significantly increased. The levels of CCK in the mucosal membrane and plasma were significantly higher in IBS-D patients than in healthy controls, and SERT showed the opposite trend. The expression of CCK was positively correlated with the severity of abdominal pain, and the level of SERT was negatively correlated with the severity of abdominal pain and visceral sensitivity.

Research conclusions

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.

Research perspectives

Our study determined the role of SERT and CCK in the pathogenesis of IBS-D. There are some limitations in our study. First, only IBS-D patients were included, and selection bias could limit the generalization to other types of IBS patients. Second, only patients from one hospital were recruited. Third, the sample size was small. According to the existing research results, no causal inferences can be made. Therefore, more carefully designed clinical studies are needed.