Abstract
Renal injury is a common complication of hyperuricemia (HUA), which has been recognized as an independent risk factor for chronic kidney disease (CKD). The gut-kidney axis theory suggests that targeting the gut microbiota may be a potential treatment option for kidney disease. In this study, we utilized a spontaneous HUA rat model to demonstrate that Simiao decoction (SMD), a traditional Chinese medicine formula, can effectively alleviate HUA-induced renal injury by modulating gut microbiota and bacterial metabolism of tryptophan and tyrosine, thereby reducing gut-derived uremic toxins such as indoxyl sulfate (IS) and p-Cresol (PC). Fecal microbiota transplantation (FMT) further confirmed that the therapeutic effect of SMD was mediated by gut microbiota. Finally, in vitro studies revealed that IS promotes epithelial-mesenchymal transition (EMT) while PC induces cellular senescence in tubular cells. Collectively, our findings suggest that SMD can effectively alleviate HUA-induced renal injury through regulating gut dysbiosis and decreasing gut-derived uremic toxins. This study sheds light on a novel mechanism by which SMD exerts its effects on HUA-induced renal injury.
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Data availability
The shallow genome sequencing is available from the NCBI Sequence Read Archive (SRA) database (Bioproject: *PRJNA1135458*). The data for this study were available by contacting the corresponding author upon reasonable request.
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Acknowledgements
This work was supported by the Joint Funds of National Natural Science Foundation of China [grant number U22A20365], National Natural Science Foundation of China [grant number 82274499, T2341019, 82405279], the Key Project of National Natural Science Foundation of China [grant number 81830117], the Guangzhou Science and Technology Plan Project [grant number 2024B03J1343], the Major scientific and technological project of Guangzhou Municipal Health Commission [grant number 20252D003], Guangdong Basic and Applied Basic Research Foundation, China [grant number 2023A1515110757], Dongguan social development technology program (High level hospital constructon project), China [grant number 20231800913372].
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Xiaoshan Zhao and Yanyan Liu designed the study and supervised the project; Xinghong Zhou, Xiaoyu Liu, Baizhao Peng and Ying Yang completed the animal experiments, analyzed data and wrote the orignial manuscript; Hanqi Lu, Dexian Li, Yijian Deng and Zihao Jiang carried out metagenomic and metabolomic analysis. Chuanghai Wu, Wen Fang and Yanting You completed the in vitro experiments and histological analysis. Hiu Yee Kwan provided technical assistance and revised the manuscript. All authors have read and approved the final version of the manuscript.
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Zhou, X., Liu, X., Peng, B. et al. Simiao Decoction alleviates hyperuricemia-induced renal injury through regulating gut dysbiosis and decreasing gut-derived uremic toxins. npj Biofilms Microbiomes (2026). https://doi.org/10.1038/s41522-026-00923-x
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DOI: https://doi.org/10.1038/s41522-026-00923-x
