Observational Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Apr 27, 2025; 17(4): 105660
Published online Apr 27, 2025. doi: 10.4254/wjh.v17.i4.105660
Correlation between the interleukin-36 subfamily and gut microbiota in patients with liver cirrhosis: Implications for gut-liver axis imbalance
Yi-Zhi Pan, Wan-Ting Chen, Hao-Ran Jin, Zhen Liu, Ying-Ying Gu, Xin-Ruo Wang, Jue Wang, Jing-Jing Lin, Yan Zhou, Lan-Man Xu
Yi-Zhi Pan, Wan-Ting Chen, Hao-Ran Jin, Zhen Liu, Ying-Ying Gu, Jue Wang, Jing-Jing Lin, Yan Zhou, Lan-Man Xu, Department of Infectious Diseases and Liver Diseases, Lihuili Hospital of Ningbo University, Ningbo 315000, Zhejiang Province, China
Yi-Zhi Pan, Xin-Ruo Wang, Lan-Man Xu, Department of Infectious Diseases and Liver Diseases, People’s Hospital of Ningbo University, Ningbo 315000, Zhejiang Province, China
Wan-Ting Chen, Department of Rheumatology and Immunology, Ningbo Hangzhou Bar Hospital, Ningbo 315000, Zhejiang Province, China
Co-first authors: Yi-Zhi Pan and Wan-Ting Chen.
Author contributions: Pan YZ is responsible for conceptualization, methodology, validation, formal analysis, investigation, data curation, and writing-original draft; Chen WT and Jin HR is responsible for conceptualization, methodology, validation, investigation, data curation, and writing-original draft; Pan YZ, Liu Z, Gu YY, Wang XR, Wang J, Lin JJ and Zhou Y is responsible for investigation and resources; Xu LM is responsible for resources, supervision, and writing-review & editing. Pan YZ and Chen WT contributed equally to this work as co-first authors.
Supported by Key Project of the Ningbo Natural Science Foundation, Zhejiang Province, China, No. 2022J253; Key Technology R&D Project of Ningbo City, No. 2023Z208; Traditional Chinese Medicine project, Zhejiang Province, No. 2024ZF028; and the Key Project of Health Science and Technology Foundation, Zhejiang Province, China, No. WKJ-ZJ-2551.
Institutional review board statement: The study protocol was reviewed and approved by the Institutional Review Board of Ningbo Medical Center Lihuili Hospital (Approval Number: 2022PJ064). The study was conducted in accordance with the principles of the Declaration of Helsinki, and all participants provided written informed consent prior to enrollment.
Informed consent statement: All participants involved in this study provided written informed consent prior to enrollment.
Conflict-of-interest statement: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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: Our original contributions are reflected in the paper/supplementary material. For in-depth inquiries, the corresponding authors can be contacted directly.
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: Lan-Man Xu, MD, PhD, Chief Physician, Professor, Department of Infectious Diseases and Liver Diseases, Lihuili Hospital of Ningbo University, No. 1111 Jiangnan Road, High-tech Zone, Ningbo 315000, Zhejiang Province, China. 13587646315@163.com
Received: February 5, 2025
Revised: March 20, 2025
Accepted: April 1, 2025
Published online: April 27, 2025
Processing time: 81 Days and 1.7 Hours
Abstract
BACKGROUND

Liver cirrhosis (LC) affect millions of people worldwide. The pathogenesis of cirrhosis involves complex interactions between immune responses and gut microbiota. Recent studies have highlighted the role of the interleukin-36 (IL-36) subfamily in inflammation and immune regulation. However, the relationship between serum IL-36 subfamily levels and gut microbiota in cirrhosis patients remains unclear. This study aimed to explore the clinical significance of serum IL-36 subfamily levels and their association with gut microbiota in cirrhosis patients.

AIM

To explore the clinical significance of serum IL-36 subfamily levels and their relationship with gut microbiota among cirrhosis patients.

METHODS

Sixty-one cirrhosis patients were enrolled from Lihuili Hospital of Ningbo University from May 2022 to November 2023 as the LC group and 29 healthy volunteers as the healthy control (HC) group. The serum expressions of IL-36α, IL-36β, IL-36γ, IL-36Ra, and IL-38 were measured through ELISA, while 16S rRNA gene sequencing was employed to rate microbial community in human fecal samples.

RESULTS

The serum levels of IL-36α, IL-36γ, IL-36Ra, and IL-38 in the LC group remarkably exceeded those in the HC group (P < 0.05). IL-36α, IL-36γ, and IL-38 were related positively to the Child-Pugh score (P < 0.05) and prominently exceeded those in the Child-Pugh C group (P < 0.05). The absolute abundance of harmful bacteria (Bacteroides, Bifidobacterium, Faecalibacterium) remarkably rose, while the beneficial bacteria (Firmicutes, Bacteroides, Escherichia-Shigella) notably decreased in the LC group (P < 0.05). IL-36α, IL-36γ, and IL-38 related positively to Lactobacillus(P < 0.05), while IL-38 negatively related to Fusicatenibacter (P < 0.05).

CONCLUSION

IL-36γ and IL-38 show promise as potential biomarkers for LC progression, but further validation is required.

Keywords: Interleukin-36; Interleukin-36γ; Interleukin-38; Liver cirrhosis; Gut microbiota

Core Tip: This study investigated the clinical relevance of serum interleukin-36 (IL-36) subfamily levels and their correlation with gut microbiota in 61 patients with liver cirrhosis (LC) and 29 healthy controls. We found that IL-36α, IL-36γ, IL-36Ra, and IL-38 Levels were significantly higher in cirrhosis patients and strongly correlated with disease progression. These cytokines may serve as novel predictive markers for LC. Our findings highlight the potential of IL-36 subfamily members as diagnostic biomarkers, contributing valuable insights to the field.