Characteristics of gut microbiota and metabolites in patients with ulcerative colitis with fatigue

doi:10.3748/wjg.v32.i3.115264

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. Jan 21, 2026; 32(3): 115264
Published online Jan 21, 2026. doi: 10.3748/wjg.v32.i3.115264

Characteristics of gut microbiota and metabolites in patients with ulcerative colitis with fatigue

Zi-Xuan Liu, Xiao-Yan Liu, Wei-Wei Tan, Wei-Bing Zhang, Ya-Li Zhang, Lie Zheng, Yan-Cheng Dai

Zi-Xuan Liu, Xiao-Yan Liu, Wei-Wei Tan, Wei-Bing Zhang, Yan-Cheng Dai, Department of Gastroenterology, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China

Ya-Li Zhang, Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China

Lie Zheng, Department of Gastroenterology, Shaanxi Hospital of Traditional Chinese Medicine, Shaanxi Academy of Traditional Chinese Medicine, Xi'an 710003, Shaanxi Province, China

Co-first authors: Zi-Xuan Liu and Xiao-Yan Liu.

Co-corresponding authors: Lie Zheng and Yan-Cheng Dai.

Author contributions: Liu ZX and Liu XY contribute equally to this study as co-first authors; Zheng L and Dai YC contribute equally to this study as co-corresponding authors; Dai YC and Zheng L designed and conceptualized the study; Liu ZX and Liu XY drafted the manuscript; Tan WW, Zhang WB, and Zhang YL contributed to the study plan; Liu ZX and Dai YC revised and edited the manuscript; all authors have read and agreed to the published version of the manuscript.

Supported by National Natural Science Foundation of China, No. 81873253 and No. 82574996; the Shanghai Natural Science Foundation, No. 22ZR1458800; the Scientific Research Project Plan of Shanghai Municipal Health Commission, No. 202240385; Hongkou District Health Committee, No. HKZK2020A01; Shaanxi Province Traditional Chinese Medicine Research and Innovation Talent Plan Project, No. TZKN-CXRC-16; Project of Shaanxi Administration of Traditional Chinese Medicine, No. SZY-KJCYC-2025-JC-010; and Shaanxi Province Key Research and Development Plan Project-Social Development Field, No. 2025SF-YBXM-498.

Institutional review board statement: This study was approved by the Ethics Committee of Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine (Approval No. 2022-053-1).

Informed consent statement: All participate will be required to sign written informed consent.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

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.

Data sharing statement: Data is available from the corresponding author on a reasonable request.

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: Yan-Cheng Dai, PhD, Department of Gastroenterology, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, No. 230 Baoding Road, Hongkou District, Shanghai 200082, China. daiyancheng2005@126.com

Received: October 15, 2025
Revised: November 19, 2025
Accepted: December 10, 2025
Published online: January 21, 2026
Processing time: 96 Days and 0.6 Hours

Abstract

BACKGROUND

Ulcerative colitis (UC) is a chronic, non-specific inflammatory bowel disease. The gut microbiome undergoes significant changes in UC. Fatigue is a highly prevalent and debilitating extraintestinal symptom of UC, which negatively affects quality of life. However, its relationship with gut microbes and metabolites remains unclear.

AIM

To assess the gut microbiota and metabolomic characteristics of patients with UC with fatigue (HUCF).

METHODS

A total of 120 participants were recruited and divided into four groups (n = 30 per group) based on the diagnosis of UC and Fatigue Scale-14 scores: HUCF, UC without fatigue (HUCN), healthy with fatigue (HHF), and healthy without fatigue (HHN). Fresh stool samples were collected for 16S rRNA sequencing and untargeted metabolomic analysis.

RESULTS

Metabolomic analysis revealed significant differences among the four groups (principal component analysis/partial least squares discriminant analysis, P = 0.001), with differential expression of metabolites such as linoleoyl ethanolamide, arachidonoyl ethanolamide, glycocholic acid, and thromboxane (TX). Notably, TX was detected only in the HUCF group. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed alterations in eicosanoid, tryptophan, and tyrosine metabolism in the HUCF group. Microbial richness and diversity were significantly lower in the HUCF group than in the other three groups. The HUCF group showed enrichment of Hyphomicrobiales, Brucella, Eisenbergiella, Pediococcus, and Sellimonas. The HUCN group showed enrichment of Campylobacter-related taxa. The HHF group showed enrichment of Fusobacterium, Desulfovibrionaceae, and Bilophila. The HHN group showed enrichment of beneficial genera such as Adlercreutzia. Notably, Anaerococcus, a beneficial genus, was enriched in the HUCF group. Correlation analysis indicated that specific microbes (e.g., Faecalibacterium and Escherichia-Shigella) were associated with the severity of UC and fatigue.

CONCLUSION

Patients with HUCF exhibit a distinct gut microbial structure and metabolomic profile. The pro-inflammatory metabolite TX and the genus Anaerococcus are uniquely enriched in patients with HUCF, suggesting their potential roles in the development of HUCF. These findings provide novel insights and a theoretical basis for improving the clinical management of HUCF.

Keywords: Ulcerative colitis; Fatigue; Gut Microbiota; Metabolites; Thromboxane; Anaerococcus

Core Tip: The relationship between disease severity and gut microbes and metabolites in patients with ulcerative colitis (UC) with fatigue remains unclear. To investigate this relationship, we collected fresh stool samples from patients with UC with/without fatigue and healthy individuals with/without fatigue for 16S rRNA sequencing and untargeted metabolomic analysis. Results revealed the gut microbial and metabolomic characteristics of patients with UC with fatigue (HUCF). Patients with HUCF exhibited a distinct gut microbial structure and metabolomic profile. Metabolomic analysis revealed differential expression of metabolites such as linoleoyl ethanolamide, arachidonoyl ethanolamide, glycocholic acid, and thromboxane. Patients with HUCF showed a high relative abundance of Anaerococcus, a beneficial genus.