Indole-3-propionic acid exacerbates cisplatin-induced chronic kidney disease through the AHR/NF-κB signaling pathway

作者：Qian Wang, Jie Chen, Huini Chen, Dongning Liang, Zhou Hong, Juanjuan Chen, Yuan Gui, Fang Yao, Yudan Chen, Xi Zeng, Yingchun Ma, Dong Zhou, Haiyan Fu · 发表于：iScience · 年份：2025 · DOI：10.1016/j.isci.2025.114149 · 被引用次数：3 · 研究领域：Chemotherapy-induced organ toxicity mitigation、Chemotherapy-induced cardiotoxicity and mitigation、Metabolomics and Mass Spectrometry Studies

Cisplatin is a commonly used chemotherapy agent for treating various solid tumors, but its clinical application is limited by nephrotoxicity. While the potential for cisplatin to cause chronic kidney disease (CKD) following repeated administration has been underexplored, effective therapeutic strategies for cisplatin-induced CKD are lacking. We found that cisplatin-induced CKD is characterized by renal dysfunction and inflammation, along with intestinal barrier impairment. 16S rRNA and metabolomics revealed that cisplatin disrupts the gut microbiome and raises levels of tryptophan metabolites-indole-3-propionic acid (IPA). Notably, oral administration of IPA reproduced similar harmful effects in cisplatin-induced CKD. Integrated analyses of the microbiome, metabolomics, Raman spectroscopy, and DESI-MSI indicated that IPA supplementation exacerbates the production of uremic toxins linked to tryptophan metabolism and promotes the growth of pathogenic bacteria. Our findings demonstrates that IPA exacerbates renal inflammation and fibrosis by regulating AHR/NF-κB signaling pathways, altering intestinal microbiome composition, and disrupting tryptophan metabolism.