Ding WJ, Liu CQ, Tang XY, Shang ZB, Liang X, Tao T, Liu RX, Jiang QY, Qiu YF, Sun Y. Role of gut microbiota in lead-induced neural damage in diabetic mice. World J Diabetes 2026; 17(1): 112885 [DOI: 10.4239/wjd.v17.i1.112885]
Corresponding Author of This Article
Yi Sun, Department of Toxicology, Guilin Medical University, No. 1 Zhiyuan Road, Lingui District, Guilin 541000, Guangxi Zhuang Autonomous Region, China. sunyide163@163.com
Research Domain of This Article
Toxicology
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/
Jan 15, 2026 (publication date) through Jan 14, 2026
Times Cited of This Article
Times Cited (0)
Journal Information of This Article
Publication Name
World Journal of Diabetes
ISSN
1948-9358
Publisher of This Article
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
Share the Article
Ding WJ, Liu CQ, Tang XY, Shang ZB, Liang X, Tao T, Liu RX, Jiang QY, Qiu YF, Sun Y. Role of gut microbiota in lead-induced neural damage in diabetic mice. World J Diabetes 2026; 17(1): 112885 [DOI: 10.4239/wjd.v17.i1.112885]
World J Diabetes. Jan 15, 2026; 17(1): 112885 Published online Jan 15, 2026. doi: 10.4239/wjd.v17.i1.112885
Role of gut microbiota in lead-induced neural damage in diabetic mice
Wen-Jia Ding, Chao-Qun Liu, Xin-Yi Tang, Zhi-Bin Shang, Xu Liang, Tao Tao, Ru-Xi Liu, Qiong-Yun Jiang, Yan-Fang Qiu, Yi Sun
Wen-Jia Ding, Xin-Yi Tang, Zhi-Bin Shang, Xu Liang, Tao Tao, Ru-Xi Liu, Qiong-Yun Jiang, Yan-Fang Qiu, Yi Sun, Department of Toxicology, Guilin Medical University, Guilin 541000, Guangxi Zhuang Autonomous Region, China
Chao-Qun Liu, School of Medicine, Jinan University, Guangzhou 510000, Guangdong Province, China
Co-first authors: Wen-Jia Ding and Chao-Qun Liu.
Author contributions: Ding WJ designed the methodology; Liu CQ validated the study; Tang XY performed formal analysis; Shang ZB and Liang X conducted animal experiments; Ding WJ curated the data; Ding WJ and Sun Y wrote the original draft; Sun Y reviewed and edited the manuscript; Tao T, Liu RX, and Jiang QY contributed to data analysis; Qiu YF administered the project; Liu CQ and Sun Y acquired the funding. Ding WJ and Liu CQ contributed equally to this work as co-first authors.
Supported by National Natural Science Foundation of China, No. 82060586; Natural Science Foundation of Guangdong Province, No. 2023GXNSFAA026122; China Scholarship Council, No. 202208455012; and National Guangxi College Students Innovation and Entrepreneurship Training Program, No. S202410601154, No. X202310601246, and No. X202310601245.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of Guilin Medical University.
Conflict-of-interest statement: The authors of this manuscript have no conflicts of interest to disclose.
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: No additional data are 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: Yi Sun, Department of Toxicology, Guilin Medical University, No. 1 Zhiyuan Road, Lingui District, Guilin 541000, Guangxi Zhuang Autonomous Region, China. sunyide163@163.com
Received: August 13, 2025 Revised: September 19, 2025 Accepted: November 28, 2025 Published online: January 15, 2026 Processing time: 159 Days and 3.3 Hours
Abstract
BACKGROUND
China has the highest incidence of diabetes among all Asian countries, and environmental factors have a significant impact on the onset of diabetes. Lead is one of the important legacy environmental pollutants that disrupts endocrine function. Both lead and diabetes have damaging effects on the nervous system, while the gut microbiota is considered an important mediator of brain damage.
AIM
To determine the effects and underlying mechanisms of environmental lead exposure and diabetes on neural function.
METHODS
A mouse model of lead exposure and diabetes was used. Lead levels were measured using inductively coupled plasma mass spectrometry, and blood glucose levels were assessed. Immunofluorescence was used to analyze brain damage in mice. The Morris water maze was used for evaluating neural function. Neurotransmitters including vanillylmandelic acid, 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) were quantified with high performance liquid chromatography. Proteomics analysis was conducted on hippocampal brain tissue, and gut microbiota analysis was performed on colonic fecal samples. PI3K and COX2 proteins were detected by Western blotting, and then glutathione (GSH) levels in brain tissue were measured.
RESULTS
Mice in the lead-exposure diabetic model exhibited significantly elevated lead and blood glucose levels, with the most severe neural damage observed. The neurotransmitters DOPAC and HVA were markedly increased. Proteomics revealed that differential proteins were primarily involved in neural and metabolic pathways. Correlation analysis between the top 20 gut microbiota and differential proteins identified Sutterella as the most associated gut microbe with proteins. The levels of COX2, PI3K, and GSH in the mouse brain provided preliminary validation of these findings.
CONCLUSION
The coexistence of lead exposure and diabetes has an interactive effect on neural damage. This interaction appears to affect the abundance of the gut microbe Sutterella, which, through inflammation, influences the expression of related differential proteins in the brain, ultimately resulting in neural damage.
Core Tip: This study identified the additive effects of concurrent lead exposure and diabetes on neurotoxicity and provided a preliminary exploration of the mechanisms by which the gut microbiota regulated the brain differential protein expression and ultimately affected neurological function, based on proteomics and gut microbiota analysis.
