Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 14, 2025; 31(22): 108815
Published online Jun 14, 2025. doi: 10.3748/wjg.v31.i22.108815
Intermittent fasting exacerbates colon inflammation by promoting Th17 cell differentiation through inhibition of gut microbiota-derived indoleacrylic acid
Rui Fu, Peng Zhang, Jia-Wei Zhang, Yuan Hong, Bo Chen, Guo-Dong Cao
Rui Fu, Peng Zhang, Jia-Wei Zhang, Yuan Hong, Bo Chen, Guo-Dong Cao, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China.
Co-first authors: Rui Fu and Peng Zhang.
Co-corresponding authors: Bo Chen and Guo-Dong Cao.
Author contributions: Fu R contributed to project administration, visualization, experimental operation; Zhang P contributed to data curation, writing original draft; Zhang JW contributed to formal analysis, methodology; Hong Y contributed to resources, polish the article; Chen B contributed to funding acquisition, writing review and editing; Cao GD contributed to funding acquisition, supervision, writing review and editing.
Supported by the Anhui University Research Project, No. 2022AH051171; Natural Science Foundation Project of Anhui Province, No. 2408085QH271; Anhui Medical University Scientific Research Level Improvement Plan, No. 2022xkjT028; Health Research Project of Anhui Province, No. AHWJ2023A30047; the Anhui Provincial Natural Science Foundation, No. 2208085MH240; the Scientific Research Project of Anhui Provincial Department of Education, No. 2022AH051167; the Anhui Quality Engineering Project, No. 2023sx200, No. 2023jyjxggyjY087 and No. 2023zyxwjxalk046; the Anhui Provincial Postgraduate Education Quality Project, No. 2024cxcysj062; and Anhui Medical University Graduate Research and Practice Innovation Project, No. YJS20240095.
Institutional review board statement: This study does not involve any human experiments.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Anhui Medical University (No. LLSC20242418).
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: Technical appendix, statistical code, and dataset available from the corresponding author at 11718242@zju.edu.cn. Consent was not obtained but the presented data are anonymized and risk of identification is low. The 16S rRNA gene sequencing data (accession number: PRJNA1259772), transcriptomic data (accession number: PRJNA1260448), and multi-omics dataset related to Th17 cell differentiation (accession number: OMIX010115) are publicly available.
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: Guo-Dong Cao, MD, PhD, Doctor, Associate Professor, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, Anhui Province, China. 11718242@zju.edu.cn
Received: April 27, 2025
Revised: May 10, 2025
Accepted: May 26, 2025
Published online: June 14, 2025
Processing time: 49 Days and 16.3 Hours
Abstract
BACKGROUND

Intermittent fasting (IF), particularly time-restricted feeding (TRF), is increasingly popular has gained popularity for weight loss, yet management, but its effects impact on gut health remain unclear. Remains inadequately understood. This study explores how investigated the effects of TRF effects on intestinal health and explored the underlying mechanisms.

AIM

To assess the effects of IF on intestinal health, elucidate the mechanisms involved.

METHODS

Mice were divided into two groups: Normal control (NC) and IF. The IF group underwent TRF, while the NC group had unrestricted access to food. Body weight, fecal characteristics, and intestinal morphology were analyzed. Colon tissue, serum, and fecal samples were collected for histological analysis, enzyme-linked immunosorbent assay, flow cytometry, 16S rRNA sequencing, and metabolomic profiling.

RESULTS

IF significantly affected body weight and intestinal morphology, compromised the intestinal barrier, increased pro-inflammatory cytokines, and heightened gut immune activation (P < 0.05). It also disrupted the gut microbiota, promoting pro-inflammatory bacteria, reducing anti-inflammatory metabolites, and elevating pro-inflammatory metabolites (P < 0.05). Indoleacrylic acid (IAA) supplementation notably alleviated intestinal inflammation and reversed immune dysfunction induced by IF (P < 0.05).

CONCLUSION

Prolonged IF exacerbates intestinal inflammation by impairing gut barrier integrity and disrupting microbial homeostasis. However, IAA supplementation effectively mitigates fasting-induced intestinal inflammation and immune imbalance, suggesting its potential as a therapeutic agent.

Keywords: Intermittent fasting; Colon inflammation; Th17 cell; Gut microbiota; Metabolomics

Core Tip: This study demonstrates that long-term intermittent fasting (IF) compromises intestinal barrier function, alters the metabolite profile (reducing anti-inflammatory compounds and increasing pro-inflammatory ones), and induces dysbiosis (increasing pathogenic bacteria while decreasing short-chain fatty acid-producing bacteria), which collectively promote Th17-driven inflammation. Exogenous indoleacrylic acid supplementation restores barrier integrity, suppresses Th17 activation, and enhances interleukin-10 expression, highlighting its therapeutic promise and emphasizing the need for a reevaluation of the long-term safety of IF due to its potential gut-disrupting effects.