Administration of Lactobacillus reuteri Combined with Clostridium butyricum Attenuates Cisplatin-Induced Renal Damage by Gut Microbiota Reconstitution, Increasing Butyric Acid Production, and Suppressing Renal Inflammation

• Published in: Nutrients Vol. 13; no. 8; p. 2792
• Main Authors: Hsiao, Yu-Ping, Chen, Hsiao-Ling, Tsai, Jen-Ning, Lin, Meei-Yn, Liao, Jiunn-Wang, Wei, Meng-Syuan, Ko, Jiunn-Liang, Ou, Chu-Chyn
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 15.08.2021; MDPI
• Subjects: apoptosis; Bifidobacterium; blood; butyric acid; Cancer therapies; Chemotherapy; cisplatin; Clostridium butyricum; collagen; dysbiosis; endotoxins; Enterobacteriaceae; epithelium; Feces; fibronectins; fibrosis; Gut microbiota; Inflammation; intestinal microorganisms; intestines; Lactobacillus reuteri; microbiome; Microbiota; Mucositis; nephrotoxicity; oxidative stress; Probiotics; protective effect; Proteins; renoprotective effect; Ruminococcaceae; sulfates; Tumors; Minneapolis Minnesota; United Kingdom > UK; United States > US; Taiwan
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu13082792

Cisplatin-induced nephrotoxicity is associated with gut microbiota disturbance. The present study aimed to investigate whether supplementation of Lactobacillus reuteri and Clostridium butyricum (LCs) had a protective effect on cisplatin-induced nephrotoxicity through reconstruction of gut microbiota. Wistar rats were given different treatments: control, cisplatin (Cis), cisplatin + C. butyricum and L. reuteri (Cis+LCs), and C. butyricum and L. reuteri (LCs). We observed that cisplatin-treated rats supplemented with LCs exhibited significantly decreased renal inflammation (KIM-1, F4/80, and MPO), oxidative stress, fibrosis (collagen IV, fibronectin, and a-SMA), apoptosis, concentration of blood endotoxin and indoxyl sulfate, and increased fecal butyric acid production compared with those without supplementation. In addition, LCs improved the cisplatin-induced microbiome dysbiosis by maintaining a healthy gut microbiota structure and diversity; depleting Escherichia-Shigella and the Enterobacteriaceae family; and enriching probiotic Bifidobacterium, Ruminococcaceae, Ruminiclostridium_9, and Oscillibacter. Moreover, the LCs intervention alleviated the cisplatin-induced intestinal epithelial barrier impairment. This study indicated LCs probiotic serves as a mediator of the gut–kidney axis in cisplatin-induced nephrotoxicity to restore the intestinal microbiota composition, thereby suppressing uremic toxin production and enhancing butyrate production. Furthermore, the renoprotective effect of LCs is partially mediated by increasing the anti-inflammatory effects and maintaining the integrity of the intestinal barrier.