Gut microbiota accelerates cisplatin-induced acute liver injury associated with robust inflammation and oxidative stress in mice

Journal of Translational Medicine

Jingrui Chen¹  Siyou Zhang¹  Yinglin Feng¹  Rong Wu¹  Xia Chen¹  Fangjie He¹  Songhua Yuan¹  Shenhai Gong²  Jiuling Lu³  Huanrui Zhang⁴  Meiping Pan⁴  Yunong Zeng⁴ 

[1] Department of Obstetrics and Gynecology, First People’s Hospital of Foshan, Foshan, China;Department of Obstetrics and Gynecology, First People’s Hospital of Foshan, Foshan, China;School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China;Department of Outpatient, First People’s Hospital of Foshan, Foshan, China;School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China;

关键词: Gut microbiota;    Cisplatin;    Hepatotoxicity;    Inflammation;    Oxidative stress;   

DOI  :  10.1186/s12967-021-02814-5

来源: Springer

【 摘 要 】

BackgroundGut microbiota has been reported to be disrupted by cisplatin, as well as to modulate chemotherapy toxicity. However, the precise role of intestinal microbiota in the pathogenesis of cisplatin hepatotoxicity remains unknown.MethodsWe compared the composition and function of gut microbiota between mice treated with and without cisplatin using 16S rRNA gene sequencing and via metabolomic analysis. For understanding the causative relationship between gut dysbiosis and cisplatin hepatotoxicity, antibiotics were administered to deplete gut microbiota and faecal microbiota transplantation (FMT) was performed before cisplatin treatment.Results16S rRNA gene sequencing and metabolomic analysis showed that cisplatin administration caused gut microbiota dysbiosis in mice. Gut microbiota ablation by antibiotic exposure protected against the hepatotoxicity induced by cisplatin. Interestingly, mice treated with antibiotics dampened the mitogen-activated protein kinase pathway activation and promoted nuclear factor erythroid 2-related factor 2 nuclear translocation, resulting in decreased levels of both inflammation and oxidative stress in the liver. FMT also confirmed the role of microbiota in individual susceptibility to cisplatin-induced hepatotoxicity.ConclusionsThis study elucidated the mechanism by which gut microbiota mediates cisplatin hepatotoxicity through enhanced inflammatory response and oxidative stress. This knowledge may help develop novel therapeutic approaches that involve targeting the composition and metabolites of microbiota.

【 授权许可】

CC BY