AccScience Publishing / AJWEP / Online First / DOI: 10.36922/AJWEP026300204
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ORIGINAL RESEARCH ARTICLE

Lead acetate exposure alters renal water reabsorption and gut microbiota in mice: Potential involvement of cerebral cavernous malformations 3 and the gut–kidney axis

Feiyu Zhao1† ,  Liuxue Yang2† ,  Dan Liang3† ,  Xu Liang1 ,  Hang Zhou1 ,  Ying Zhang1 ,  Xinru Liang1 ,  Jiaomin He1 ,  Xinru Ma1 ,  Muyao Chen4 ,  Yi Sun1,5*
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1 Department of Toxicology, School of Public Health, Guilin Medical University, Guilin, Guangxi , China
2 Department of Science Experiment Center, School of Public Health, Guilin Medical University, Guilin, Guangxi , China
3 Department of Endocrinology, The Second Affiliated Hospital of Guilin Medical College, Guilin, Guangxi , China
4 Department of Biology, Tongji University High School (Sci-Tech), Shanghai , China
5 Department of Environmental and Occupational Medicine, School of Public Health, Guilin Medical University, The Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Heath, Guilin, Guangxi , China
†These authors contributed equally to this work.
AJWEP, 026300204 https://doi.org/10.36922/AJWEP026300204
Received: 25 July 2026 | Revised: 27 August 2026 | Accepted: 10 September 2026 | Published online: 28 October 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Lead is a widespread, cumulative environmental pollutant with confirmed renal and gastrointestinal toxicity, but the mechanism underlying lead-induced alterations in renal water reabsorption and the potential role of the gut–kidney axis remain unclear. This study aims to explore the potential role of cerebral cavernous malformations 3 (CCM3) in lead-induced alteration of renal tubular water reabsorption and its potential association with the gut–kidney axis. C57BL/6J mice were administered drinking water containing 0.05%, 0.25%, and 0.5% lead acetate for 30 days. Urine was collected weekly for quantitative analysis. After exposure, a desmopressin (dAVP) challenge test was performed. Blood lead concentration was detected by inductively coupled plasma mass spectrometry. Kidney tissues were evaluated by hematoxylin and eosin (H&E) staining and Western blot. Fecal samples were collected before and after exposure for 16S rRNA gut microbiota sequencing. Data were analyzed by repeated-measures analysis of variance (ANOVA) and one-way ANOVA using GraphPad Prism 8.0. As exposure dose increased, blood lead concentration increased dose-dependently in all exposure groups. Urine output decreased significantly in medium- and high-dose groups after 24-hour water deprivation and dAVP challenge. H&E staining showed dose-dependent renal tubular necrosis. The composition and diversity of gut microbiota were significantly altered. Renal CCM3 protein expression was significantly increased (most prominent in the medium-dose group), glutathione peroxidase 4 (GPX4) protein was significantly decreased in the high-dose group, and aquaporin (AQP) 2 and AQP4 proteins showed an upward trend without statistical significance. Lead exposure induces renal tubular structural injury and alters renal water reabsorption function. This process may be associated with gut microbiota dysbiosis, which affects renal CCM3 expression via the gut–kidney axis and further regulates AQP2/4 levels through GPX4-related pathways. This study provides preliminary correlational evidence and proposes a testable hypothesis for future mechanistic research.

Keywords
Lead
Cerebral cavernous malformations 3
Glutathione peroxidase 4
Aquaporin 2/4
Gut–kidney axis
Funding
This work was supported in part by the National Natural Science Foundation of China ( 8266120278, 82060586), the Natural Science Foundation of Guangxi Province (2025GXNSFHA069136, 2023GXNSFAA026122), the China Scholarship Council (CSC, 202208455012), and the National Guangxi College Students Innovation and National Guangxi College Students Innovation and Entrepreneurship Training Program (S202510601199, X202410601232).
Conflict of interest
The authors declare that they have no competing interests for this research.
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Asian Journal of Water, Environment and Pollution, Electronic ISSN: 1875-8568 Print ISSN: 0972-9860, Published by AccScience Publishing
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