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ORIGINAL RESEARCH article

Front. Microbiol.
Sec. Microorganisms in Vertebrate Digestive Systems
Volume 15 - 2024 | doi: 10.3389/fmicb.2024.1348403
This article is part of the Research Topic Rodent model organisms: Therapeutic treatments and drugs interaction with the gut microbiome View all 38 articles

Alterations in the gut microbiome and metabolism with doxorubicin-induced heart failure severity

Provisionally accepted
Zekun Wang Zekun Wang 1Qian Wang Qian Wang 2Long Li Long Li 3Chenyang Wang Chenyang Wang 3Shuling Rong Shuling Rong 4Xuedong Zhou Xuedong Zhou 5*
  • 1 State Key Laboratory of Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, Sichuan Province, China
  • 2 Shanxi Provincial Key Laboratory of Brain Science and Neuropsychiatric Diseases, Taiyuan, Shanxi Province, China
  • 3 Key Laboratory of Cardiovascular Medicine and Clinical Pharmacology of Shanxi Province, Taiyuan, Shanxi Province, China
  • 4 Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China
  • 5 State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, State Key Laboratory of Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China

The final, formatted version of the article will be published soon.

    Objective: This study aimed to explore the changes in gut microbiota and its metabolites in different pathophysiological stages of doxorubicin (DOX)-induced heart failure (DIHF) and the relationship between gut microbiota and metabolites in various degrees of DIHF.Materials and methods: C57BL/ 6J mice were injected intraperitoneally with 5 mg/kg of DOX once a week for five consecutive weeks. At different times after injection, the cardiac function and histopathological analysis was conducted, the serum levels of creatine kinase, CK-MB, lactic dehydrogenase, and cardiac troponin T were determined. 16S rRNA gene sequencing of feces and the nontargeted metabolomics analysis of serum were performed. Multi-omics analyses were used to explore the correlation between gut microbiota and serum metabolites.The results showed that DOX caused left ventricular (LV) dilation and reduced LV contractility. The levels of myocardial enzymes significantly increase in 3 and 5 weeks after DOX injection. DOX-treated mice showed significant differences in the composition and abundance of gut microorganisms, and the levels of serum metabolites at different times of treatment. Multi-omics analyses showed that intestinal bacteria were significantly correlated with the differential metabolites. Some bacteria and metabolites can be used as biomarkers of DIHF (AUC > 0.8). KEGG analyses showed the involvement of different metabolic pathways in various degrees of DIHF from the control mice.: Marked differences were found in the composition and abundance of gut microorganisms, the levels of serum metabolites and metabolic pathways in different degrees of DIHF. The intestinal bacteria were significantly correlated with differential metabolites in different degrees of DIHF. The gut microbiota may serve as new targets for the treatment of DIHF.

    Keywords: Doxorubicin, Heart Failure, Gut Microbiota, 16S rRNA gene sequencing, Metabolomics, multivariate analysis

    Received: 11 Dec 2023; Accepted: 14 Aug 2024.

    Copyright: © 2024 Wang, Wang, Li, Wang, Rong and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Xuedong Zhou, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, State Key Laboratory of Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China

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