Guo HJ, Ma XQ, Li YT, Zhou ZH, Tao W, Jiang YH, Li XL, Zhang XL. Correlation between depressive-like behavior and gut microbiota in mice with hypothyroidism. World J Psychiatry 2025; 15(7): 104921 [DOI: 10.5498/wjp.v15.i7.104921]
Corresponding Author of This Article
Xi-Liang Zhang, MD, Department of General Surgery, School of Medicine, South China University of Technology, Guangzhou University Town, Panyu District, Guangzhou 510005, Guangdong Province, China. doctor_zxl1978@126.com
Research Domain of This Article
Microbiology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
Han-Jie Guo, Xiao-Qing Ma, Xi-Liang Zhang, Department of General Surgery, School of Medicine, South China University of Technology, Guangzhou 510005, Guangdong Province, China
Han-Jie Guo, Wei Tao, Yu-Hao Jiang, Xiao-Long Li, Xi-Liang Zhang, Department of General Surgery, Xinqiao Hospital, Army Medical University, Chongqing 400037, China
Yan-Ting Li, Department of Anesthesiology, Guangzhou First People’s Hospital, Guangzhou 510180, Guangdong Province, China
Zhao-Han Zhou, Department of Radiology, Shantou Central Hospital, Shantou 515041, Guangdong Province, China
Co-first authors: Han-Jie Guo and Xiao-Qing Ma.
Co-corresponding authors: Xiao-Long Li and Xi-Liang Zhang.
Author contributions: Zhang XL and Li XL designed the study and contributed equally as co-corresponding authors; Guo HJ and Ma XQ conducted research and processed data, they contributed equally as co-first authors; Guo HJ and Li YT wrote the first draft of the manuscript; Zhou ZH, Tao W, and Jiang YH revised the manuscript; all authors read and approved the final manuscript.
Supported by Beijing Science and Technology Project, No. Z191100006619059.
Institutional animal care and use committee statement: All animal experiments were conducted following the protocols approved by the Institutional Animal Care and Use Committee (IACUC) of Army Medical University, China (Approval No. AMUWE20244492).
Conflict-of-interest statement: The authors report no relevant conflicts of interest for this article.
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 data that support the findings of this study are available from the corresponding author upon 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: Xi-Liang Zhang, MD, Department of General Surgery, School of Medicine, South China University of Technology, Guangzhou University Town, Panyu District, Guangzhou 510005, Guangdong Province, China. doctor_zxl1978@126.com
Received: February 7, 2025 Revised: March 18, 2025 Accepted: May 16, 2025 Published online: July 19, 2025 Processing time: 152 Days and 19 Hours
Abstract
BACKGROUND
The association between hypothyroidism and depression is well established, but the underlying mechanisms remain unclear.
AIM
To explore the potential role of the gut microbiota in depressive-like behaviors in a mouse model of hypothyroidism, with a focus on bacterial composition.
METHODS
Hypothyroidism was induced in mice using propylthiouracil. Depressive-like behaviors were assessed using the sucrose preference test (SPT), forced swimming test (FST), tail suspension test (TST), and open field test (OFT). Inflammatory cytokines, including interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α, and IL-10, were quantified, together with colon histopathology scores, brain-derived neurotrophic factor, nuclear factor κB, inhibitor of nuclear factor κB, and tight junction proteins (occludin, claudin-1, zonula occludens-1). Gut microbial composition was determined by 16S rRNA gene sequencing of fecal samples.
RESULTS
Propylthiouracil-treated mice exhibited pronounced depressive-like behaviors, intestinal barrier dysfunction, elevated peripheral and central inflammation, and gut microbiota dysbiosis. Pearson correlation analysis showed that Bilophila and Psychrobacter abundance positively correlated with sucrose preference in the SPT and locomotor activity in the OFT, and negatively correlated with immobility times in the FST and TST. Gordonibacter abundance was positively correlated with locomotion in the OFT and negatively correlated with immobility in the FST and TST. Prevotellaceae_UCG_001 was inversely correlated with immobility in the FST and TST. Streptococcus was positively associated with sucrose preference in the SPT.
CONCLUSION
The observed associations between specific bacterial taxa and behavioral indices support a potential connection between gut microbiota composition and depressive symptoms in mice with hypothyroidism.
Core Tip: Our research has found that hypothyroidism-induced depression is associated with gut microbiota dysbiosis, and the intestinal barrier dysfunction and the activation of peripheral and central inflammation play important roles between the two. Furthermore, through Pearson correlation analysis, we found that specific bacterial genera including Bilophila and Gordonibacter, correlate with depressive-like behaviors, suggesting that microbiota-targeted interventions may offer therapeutic benefits for depression associated with hypothyroidism.
