Butyrate ameliorate doxorubicin-induced heart failure via microbiota/ metabolites-gut-Heart axis

ABSTRACT: Doxorubicin(DOX) is widely used in cancer chemotherapy with a limitation of DOX-induced cardiotoxicity(DIC),resulting in heart failure(HF).HF accompanies by gut microbial dysbiosis.However,how gut microbiota regulate DIC-induced heart failure (DIHF)remains unclear.Here, we established a susceptibility model of DIHF,confirming that gut microbiota play a critical role in regulating DIHF. In the DIHF-high susceptibility group the abundance of butyrate-producing bacteria was significantly reduced, fecal and serum butyrate level was lowered, and lipid metabolism was disordered,compared with control group. Sodium butyrate(NaB) reduces DOX-induced cardiomyocyte toxicity in vitro.Orally supplemental NaB increases the biodiversity of gut microbiota,optimizes the composition of gut microbiota, reduces serum total cholesterol level, thereby ameliorates HF in vivo. Mechanistically,supplemental NaB increases the concentration of serum and cardiac butyrate, enhances the barrier function of colonic and cardiac tissues, reduces gut microbiota translocation to heart and LPS level,results in significant differences in the microbiota composition in cardiac tissue, promotes the polarization of M1 macrophages to M2, increases the level of anti-inflammatory factors, and decreases the level of pro-inflammatory factors. NaB reduces ferroptosis of DOX-induced cardiomyocyte via GPX4/GSH pathway. Collectively,these findings demonstrate that Butyrate ameliorates DIHF via microbiota/metabolites-gut-heart axis,offering a potential prevention and therapeutic strategy for DIHF.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

PROVIDER: MTBLS11819 | MetaboLights | 2025-09-12

REPOSITORIES: MetaboLights