Case Control Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 28, 2020; 26(48): 7633-7651
Published online Dec 28, 2020. doi: 10.3748/wjg.v26.i48.7633
Gegen Qinlian decoction enhances immunity and protects intestinal barrier function in colorectal cancer patients via gut microbiota
Yang Li, Zhong-Xin Li, Chen-Yang Xie, Jing Fan, Ji Lv, Xin-Jian Xu, Jian Lv, Wen-Tao Kuai, Yi-Tao Jia
Yang Li, Jing Fan, Wen-Tao Kuai, Yi-Tao Jia, Department of Oncology, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China
Yang Li, Department of Oncology, Affiliated Hospital of Hebei University, Baoding 071000, Hebei Province, China
Zhong-Xin Li, Chen-Yang Xie, Second Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
Ji Lv, Department of Surgery, The First Hospital of Qinhuangdao, Qinhuangdao 066000, Hebei Province, China
Xin-Jian Xu, Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
Jian Lv, Department of Emergency, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China
Author contributions: Jia YT and Li ZX made substantial contributions to the conception and design of the study; Li Y searched and reviewed published articles and wrote the manuscript; Li Y, Xie CY and Lv J collected patient data and prepared the tables; Li Y and Fan J tested the relevant experiments in the manuscript, statistically analyzed the data, and prepared the figures; Lv J, Xu XJ and Kuai WT critically reviewed the article and made revisions to the manuscript; all authors approved the final version.
Institutional review board statement: The study was reviewed and approved by the Fourth Hospital of Hebei Medical University Institutional Review Board (Approval No. 2019082).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors report no conflicts of interests.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
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: Yi-Tao Jia, MD, Professor, Department of Oncology, Hebei General Hospital, No. 348 Heping West Road, Shijiazhuang 050051, Hebei Province, China. jiayitao99@163.com
Received: August 30, 2020
Peer-review started: August 30, 2020
First decision: October 17, 2020
Revised: October 31, 2020
Accepted: November 12, 2020
Article in press: November 12, 2020
Published online: December 28, 2020
Processing time: 116 Days and 1.5 Hours
Abstract
BACKGROUND

We previously showed, using the Traditional Chinese Medicine System Pharmacology Database, that Gegen Qinlian decoction (GQD) had a direct antitumor effect, and was combined with programmed cell death protein (PD)-1 inhibitors to treat microsatellite stable (MSS) tumor-bearing mice. However, the effect of GQD on patients with colorectal cancer (CRC) is not clear.

AIM

To determine the therapeutic mechanism of GQD in improving immune function, reducing inflammation and protecting intestinal barrier function.

METHODS

Seventy patients with CRC were included in this study: 37 in the control group and 33 in the treatment group. The proportions of CD4+ T, CD8+ T, natural killer (NK), NKT and T regulatory cells were measured by flow cytometry. Levels of the cytokines tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-2, IL-6, IL-10 and serotonin (5-hydroxytryptamine; 5-HT) in serum were assessed by enzyme-linked immunosorbent assay (ELISA). The expression of zonula occludens (ZO)-1, occludin, nuclear factor (NF)-κB and TNF-α in tumor and normal tissues was measured by immunohistochemistry. The composition of gut microbiota from patients in the treatment group was assessed using 16S rDNA analysis.

RESULTS

There were no adverse events in the treatment group. The proportion of CD4+ T cells and NKT cells in the post-treatment group was significantly higher than that in the pre-treatment and control groups (P < 0.05). The level of TNF-α in the post-treatment group was significantly lower than that in the pre-treatment and control groups (P < 0.05). The concentration of 5-HT in the post-treatment group was significantly lower than that in the pre-treatment group (P < 0.05). The expression of ZO-1 and occludin in tumor tissues in the treatment group was significantly higher than that in the control group (P < 0.05). The expression of ZO-1 in normal tissues of the treatment group was significantly higher than that in the control group (P = 0.010). Compared with the control group, expression of NF-κB and TNF-α in tumor tissues of the treatment group was significantly decreased (P < 0.05). Compared with the pre-treatment group, GQD decreased the relative abundance of Megamonas and Veillonella. In addition, GQD increased the relative abundance of Bacteroides, Akkermansia and Prevotella.

CONCLUSION

GQD enhances immunity and protects intestinal barrier function in patients with CRC by regulating the composition of gut microbiota.

Keywords: Colorectal cancer; Gegen Qinlian decoction; Immunity; Inflammation; Intestinal barrier function; Gut microbiota

Core Tip: On the basis of our previous study, this study revealed that Gegen Qinlian decoction (GQD) repaired intestinal barrier function in patients with colorectal cancer (CRC) by regulating gut microbiota, thereby improving immune status and reducing inflammation. Our findings highlight the therapeutic potential of GQD in modulating the gut microbiota and protecting intestinal barrier function in CRC patients.