Gut microbial-derived metabolites: key players in kidney disease and renal fibrosis
4 affiliations
- 1School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, No. 548 Binwen Road, Hangzhou, Zhejiang 310053, China
- 2School of Pharmaceutical Sciences, The First Affiliated Hospital of Zhejiang Chinese Medical University, No. 54 Youdian Road, Hangzhou 310003, China
- 3School of Medicine, Northwest University, No. 229 Taibai North Road, Xi'an, Shaanxi, 710069, China
- 4State Key Laboratory of Kidney Diseases, First Medical Center of Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing 100853, China
Abstract
Kidney disease is a major global public health problem that affects 15-20% of adults globally. Increasing evidence shows that kidney injury results in intestinal barrier dysfunction, microbial dysbiosis, and microbial-derived metabolite disorder. Microbial-derived metabolites are recognized as multi-kingdom intermediates. The alterations of the gut microbiota lead to the reductions of short-chain fatty acids including acetate, butyrate, and propionate, while excessive accumulation of uremic toxins, including indoxyl sulfate, indole-3-acetic acid, trimethylamine-N-oxide, and p-cresyl sulphate that involved in renal disease. Various effects are moderated by regulating aryl hydrocarbon receptor, G-protein-coupled receptor 43, Toll-like receptor 4, domain-like receptor family protein 3, phosphatidylinositol-3 kinase, inhibitor of kappa B /nuclear factor kappa B and kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 pathways via gut microbiota-derived metabolites. Among them, tryptophan metabolites are considered pivotal in the communication between gut microbiota and kidneys. This review summarizes current understanding of the role of gut microbial-derived metabolites in acute kidney injury and chronic kidney disease including diabetic kidney disease, immunoglobulin A nephropathy and membranous nephropathy, explain the underlying pathophysiology of these associations and pinpoint potential targets for the future precision-based modulation of therapies. This review also explores therapeutic options, such as natural products, prebiotics, probiotics, and renal replacement therapy, for targeting gut microbiota dysbiosis and their metabolites in patients with kidney diseases to provide a more concept-driven and precise therapy strategy.
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BibTeX
@article{zhang2026microbialderived,
title = {{Gut microbial-derived metabolites: key players in kidney disease and renal fibrosis}},
author = {Wan-Ying Zhang and Yu-Lu Zhang and Qing-Qing Yu and Jing-Teng Zhou and Hua Miao and Li-min Liu and Ying-Yong Zhao},
journal = {International Journal of Biological Sciences},
year = {2026},
month = may,
doi = {10.7150/ijbs.133969},
url = {https://doi.org/10.7150/ijbs.133969},
note = {CC BY},
}
RIS
TY - JOUR
TI - Gut microbial-derived metabolites: key players in kidney disease and renal fibrosis
AU - Wan-Ying Zhang
AU - Yu-Lu Zhang
AU - Qing-Qing Yu
AU - Jing-Teng Zhou
AU - Hua Miao
AU - Li-min Liu
AU - Ying-Yong Zhao
PY - 2026
DA - 2026/05/18
JO - International Journal of Biological Sciences
DO - 10.7150/ijbs.133969
UR - https://doi.org/10.7150/ijbs.133969
AB - Kidney disease is a major global public health problem that affects 15-20% of adults globally. Increasing evidence shows that kidney injury results in intestinal barrier dysfunction, microbial dysbiosis, and microbial-derived metabolite disorder. Microbial-derived metabolites are recognized as multi-kingdom intermediates. The alterations of the gut microbiota lead to the reductions of short-chain fatty acids including acetate, butyrate, and propionate, while excessive accumulation of uremic toxins, including indoxyl sulfate, indole-3-acetic acid, trimethylamine-N-oxide, and p-cresyl sulphate that involved in renal disease. Various effects are moderated by regulating aryl hydrocarbon receptor, G-protein-coupled receptor 43, Toll-like receptor 4, domain-like receptor family protein 3, phosphatidylinositol-3 kinase, inhibitor of kappa B /nuclear factor kappa B and kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 pathways via gut microbiota-derived metabolites. Among them, tryptophan metabolites are considered pivotal in the communication between gut microbiota and kidneys. This review summarizes current understanding of the role of gut microbial-derived metabolites in acute kidney injury and chronic kidney disease including diabetic kidney disease, immunoglobulin A nephropathy and membranous nephropathy, explain the underlying pathophysiology of these associations and pinpoint potential targets for the future precision-based modulation of therapies. This review also explores therapeutic options, such as natural products, prebiotics, probiotics, and renal replacement therapy, for targeting gut microbiota dysbiosis and their metabolites in patients with kidney diseases to provide a more concept-driven and precise therapy strategy.
SN - 1449-2288
ER -