Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 7, 2025; 31(17): 105411
Published online May 7, 2025. doi: 10.3748/wjg.v31.i17.105411
Ozone controls the metabolism of tryptophan protecting against sepsis-induced intestinal damage by activating aryl hydrocarbon receptor
Qing Wang, Chun-Zheng Liu, Bai-Tian Li, Xiu-Qin Yu, Jin-Yuan Zhang, Ze-Tian Wang, Li-Jun Liao, Xiao-Dong Liu
Qing Wang, Chun-Zheng Liu, Bai-Tian Li, Xiu-Qin Yu, Jin-Yuan Zhang, Department of Anesthesiology and Pain Management, Shanghai East Hospital, Shanghai 200433, China
Ze-Tian Wang, Department of Anesthesiology and Pain Management, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200240, China
Li-Jun Liao, Department of Pain Management, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200433, China
Xiao-Dong Liu, Department of Anesthesia and Intensive Care, The Chinese University of Hong Kong; Peter Hung Pain Research Institute
Co-first authors: Qing Wang and Chun-Zheng Liu.
Co-corresponding authors: Ze-Tian Wang and Li-Jun Liao.
Author contributions: Wang Q contributed to data curation, formal analysis, writing original draft; Liu CZ contributed to data curation, methodology, supervision, validation, writing-review and editing; Li BT and Liu XD contributed to formal analysis, methodology, writing original draft; Yu XQ, Zhang JY contributed to formal analysis, project administration, validation; Wang ZT contributed to writing original draft, conceptualization, investigation, software; Liao LJ contributed to funding acquisition.
Supported by the National Natural Science Foundation of China, No. 81971814; Pudong New Area Health Talent Training Program, No. 2025PDWSYCBJ-04; and Shanghai’s 2023 “Technology Innovation Action Plan” Medical Innovation Research Project, No. 23Y11908300.
Institutional review board statement: This study does not involve any human experiments.
Institutional animal care and use committee statement: This study was obtained from the Animal Center of Shanghai East Hospital Affiliated with Tongji University, Shanghai, China. The protocol was approved by the Animal Ethics Committee of Tongji University (No. TJBB07324106).
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: http://www.hmdb.ca/, MTBLS10903; https://www.ncbi.nlm.nih.gov/, PRJNA1149006.
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: Li-Jun Liao, PhD, Doctor, Department of Anesthesiology and Pain Management, Shanghai East Hospital, Tongji University School of Medicine, No. 1800 Yuntai Road, Shanghai 200240, China. liao@pan-intelligence.com
Received: January 22, 2025
Revised: March 10, 2025
Accepted: April 16, 2025
Published online: May 7, 2025
Processing time: 98 Days and 3.7 Hours
Abstract
BACKGROUND

Intestinal injury is the most common complication of sepsis, and the mitigation of intestinal damage is crucial for treating sepsis.

AIM

To examine the use of ozone-rich water and its action in preventing intestinal damage caused by sepsis.

METHODS

Through histological analysis, immunohistochemistry, immunofluorescence assays, and Western blot detection, we evaluated the therapeutic efficacy of ozone in mitigating intestinal injury during sepsis. Additionally, by conducting 16S rRNA sequencing and untargeted metabolomics analysis on fecal samples, we identified alterations in the gut microbiota and specific metabolites in septic mice following ozone treatment. This comprehensive approach aims to further elucidate the mechanistic underpinnings of ozone therapy in alleviating sepsis-induced intestinal damage.

RESULTS

Our results demonstrate that ozonated water significantly ameliorates pathological damage in intestinal tissues, enhances the expression of tight junction proteins, and inhibits the polarization of intestinal macrophages, thereby reducing the expression of inflammatory cytokines in intestinal tissues of cecal ligation and puncture-induced septic mice. 16S rRNA sequencing analysis revealed that ozonated water increased the abundance of beneficial bacteria and alleviated gut microbiota dysbiosis. Studies using broad-spectrum antibiotic-treated mice indicated that the protective effects of ozonated water on intestinal injury are dependent on the gut microbiota. Furthermore, metabolomic analysis identified an increase in the tryptophan metabolite DL-tryptophan in the ozonated water treatment group. This suggests that ozonated water protects against intestinal injury by activating the aryl hydrocarbon receptor and suppressing necroptosis in intestinal epithelial cells.

CONCLUSION

Ozone protected against sepsis-induced intestinal injury through regulation of the gut microbiota and tryptophan metabolism, inhibiting necrotic apoptosis of intestinal epithelial cells through activation of the aryl hydrocarbon receptor.

Keywords: DL-tryptophan; Necroptosis; Aryl hydrocarbon receptor; Intestinal flora; Intestinal injury; Sepsis

Core Tip: Ozone protected against sepsis-induced intestinal injury through regulation of the gut microbiota and tryptophan metabolism, inhibiting necrotic apoptosis of intestinal cells through activation of the aryl hydrocarbon receptor.