Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pharmacol Ther. Mar 5, 2023; 14(2): 4-21
Published online Mar 5, 2023. doi: 10.4292/wjgpt.v14.i2.4
Cinnamic acid regulates the intestinal microbiome and short-chain fatty acids to treat slow transit constipation
Jin-Guang Jiang, Qian Luo, Shuang-Shuang Li, Tian-Ying Tan, Kai Xiong, Tao Yang, Tian-Bao Xiao
Jin-Guang Jiang, Qian Luo, Department of Colorectal and Anal Surgery, Suqian Hospital of Traditional Chinese Medicine, Suqian 223800, Jiangsu Province, China
Shuang-Shuang Li, Tian-Ying Tan, Kai Xiong, College of Clinical Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550000, Guizhou Province, China
Tao Yang, Tian-Bao Xiao, Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang 550000, Guizhou Province, China
Author contributions: Jiang JG and Luo Q conceived the project and wrote the manuscript; Luo Q performed the central part of the experiments and analyzed data, with contributions from Li SS, Tan TY, and Xiong K; Yang T and Xiao TB participated in the experimental design and manuscript draft preparation and revision; All authors read and approved the final manuscript.
Supported by the "333 Scientific Project" of Jiangsu Province in 2020, No. BRA2020237; and the Science and Technology Project of Suqian, Jiangsu Province in 2020, No. Z2020057.
Institutional animal care and use committee statement: All animal procedures were conducted in accordance with guidelines for laboratory animal care after approval by the Ethics Committee of Suqian Hospital of Traditional Chinese Medicine.
Conflict-of-interest statement: All authors of this manuscript state that they do not have any conflict of interests, and there is nothing to disclose.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Tian-Bao Xiao, MD, Doctor, Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No. 71 Baoshan North Road, Guiyang 550000, Guizhou Province, China. prof_xiaotianbao@163.com
Received: October 15, 2022
Peer-review started: October 15, 2022
First decision: January 3, 2023
Revised: January 10, 2023
Accepted: February 21, 2023
Article in press: February 21, 2023
Published online: March 5, 2023
Processing time: 139 Days and 2.6 Hours
Abstract
BACKGROUND

Slow transit constipation (STC) is a disorder with delayed colonic transit. Cinnamic acid (CA) is an organic acid in natural plants, such as Radix Scrophulariae (Xuan Shen), with low toxicity and biological activities to modulate the intestinal microbiome.

AIM

To explore the potential effects of CA on the intestinal microbiome and the primary endogenous metabolites-short-chain fatty acids (SCFAs) and evaluate the therapeutic effects of CA in STC.

METHODS

Loperamide was applied to induce STC in mice. The treatment effects of CA on STC mice were assessed from the 24 h defecations, fecal moisture and intestinal transit rate. The enteric neurotransmitters: 5-hydroxytryptamine (5-HT) and vasoactive intestinal peptide (VIP) were determined by the enzyme-linked immunosorbent assay. Hematoxylin-eosin and Alcian blue and Periodic acid Schiff staining were used to evaluate intestinal mucosa's histopathological performance and secretory function. 16S rDNA was employed to analyze the composition and abundance of the intestinal microbiome. The SCFAs in stool samples were quantitatively detected by gas chromatography-mass spectrometry.

RESULTS

CA ameliorated the symptoms of STC and treated STC effectively. CA ameliorated the infiltration of neutrophils and lymphocytes, increased the number of goblet cells and acidic mucus secretion of the mucosa. In addition, CA significantly increased the concentration of 5-HT and reduced VIP. CA significantly improved the diversity and abundance of the beneficial microbiome. Furthermore, the production of SCFAs [including acetic acid (AA), butyric acid (BA), propionic acid (PA) and valeric acid (VA)] was significantly promoted by CA. The changed abundance of Firmicutes, Akkermansia, Lachnoclostridium, Monoglobus, UCG.005, Paenalcaligenes, Psychrobacter and Acinetobacter were involved in the production of AA, BA, PA and VA.

CONCLUSION

CA could treat STC effectively by ameliorating the composition and abundance of the intestinal microbiome to regulate the production of SCFAs.

Keywords: Slow transit constipation; Cinnamic acid; Intestinal microbiome; Short-chain fatty acids; Intestinal motility

Core Tip: Studies on the gut microbiome and its metabolites are increasingly in slow transit constipation (STC). In this study, we found that Cinnamic acid (CA) improved and treated STC effectively by ameliorating intestinal mucosa's histopathological performance and secretory function in STC mice induced by loperamide, with alpha and beta diversity significantly decreased. Meanwhile, CA ameliorated the composition and abundance of the intestinal microbiome.