Lianbi Zhao1,2, Changyang Xing1, Wenqi Sun1, Guangli Hou1, Guodong Yang3, Lijun Yuan4. 1. Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xinsi Road No. 569th, Xi'an, 710038, People's Republic of China. 2. The State Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Changlexi Road No. 169th, Xi'an, 710032, People's Republic of China. 3. The State Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Changlexi Road No. 169th, Xi'an, 710032, People's Republic of China. yanggd@fmmu.edu.cn. 4. Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xinsi Road No. 569th, Xi'an, 710038, People's Republic of China. yuanlj@fmmu.edu.cn.
Abstract
PURPOSE: Cardiotoxicity of chemotherapy exerts as the main hurdle for prognosis, while whether cisplatin causes severe cardiotoxicity remains largely unknown. Accumulating evidence reveals that intestinal microbiota functions importantly in nutrient metabolism and cardiovascular function. In this study, we observed the possible cardiotoxicity of cisplatin and explored the possible role of microbiota in the mouse model. METHODS: C57Bl6 mice were treated with 0, 3 or 6 mg/kg cisplatin via i.p. injection, together with or without Lactobacillus supplementation. Cardiac function was analyzed by echocardiography. Gut microbiota was analyzed by 16S RNA sequencing. Gene expression was analyzed by qPCR. The data differences were compared with Graphpad Prism 7.0. RESULTS: In comparison with the control group, 6 mg/kg per week cisplatin treatment for 3 weeks significantly decreased the body weight by about 33% (18.1 ± 2.1 vs 27.2 ± 0.9) and decreased the left ventricular ejection fraction by about 15% (0.57 ± 0.07 vs 0.67 ± 0.04). Together, the gut microbiota was found dramatically changed, manifested as 27% decrease of Firmicutes and increased pathological bacteria. Antibiotics treatment had no obvious beneficial effects on the body weight and cardiac function caused by cisplatin. However, Lactobacillus supplementation significantly increased the body weight and restored cardiac function, together with lower inflammation gene expression. CONCLUSIONS: The study here has established a possible role of microbiota dysbiosis in cisplatin-associated toxic effects, while delivery of Lactobacillus would be beneficial for the cardiac function prevention possibly via inflammation control.
PURPOSE:Cardiotoxicity of chemotherapy exerts as the main hurdle for prognosis, while whether cisplatin causes severe cardiotoxicity remains largely unknown. Accumulating evidence reveals that intestinal microbiota functions importantly in nutrient metabolism and cardiovascular function. In this study, we observed the possible cardiotoxicity of cisplatin and explored the possible role of microbiota in the mouse model. METHODS: C57Bl6 mice were treated with 0, 3 or 6 mg/kg cisplatin via i.p. injection, together with or without Lactobacillus supplementation. Cardiac function was analyzed by echocardiography. Gut microbiota was analyzed by 16S RNA sequencing. Gene expression was analyzed by qPCR. The data differences were compared with Graphpad Prism 7.0. RESULTS: In comparison with the control group, 6 mg/kg per week cisplatin treatment for 3 weeks significantly decreased the body weight by about 33% (18.1 ± 2.1 vs 27.2 ± 0.9) and decreased the left ventricular ejection fraction by about 15% (0.57 ± 0.07 vs 0.67 ± 0.04). Together, the gut microbiota was found dramatically changed, manifested as 27% decrease of Firmicutes and increased pathological bacteria. Antibiotics treatment had no obvious beneficial effects on the body weight and cardiac function caused by cisplatin. However, Lactobacillus supplementation significantly increased the body weight and restored cardiac function, together with lower inflammation gene expression. CONCLUSIONS: The study here has established a possible role of microbiota dysbiosis in cisplatin-associated toxic effects, while delivery of Lactobacillus would be beneficial for the cardiac function prevention possibly via inflammation control.
Authors: Gael Urait Varela-Trinidad; Carolina Domínguez-Díaz; Karla Solórzano-Castanedo; Liliana Íñiguez-Gutiérrez; Teresita de Jesús Hernández-Flores; Mary Fafutis-Morris Journal: Microorganisms Date: 2022-07-14