RNA sequencing analysis of doxorubicin-treated mice after administration with Akkermansia muciniphila
Doxorubicin (DOX) is considered as the major culprit in chemotherapy-induced cardiotoxicity, which limits its clinical application. Akkermansia muciniphila (AKK) shows a beneficial role as a probiotic in the treatment of metabolic syndrome. However, the changes of AKK during DIC and whether it mediates cardioprotective effects remains unclear. Cardiac transcriptomics certified by in vitro experiments demonstrated that AKK administration effectively improved mitochondrial function and alleviated DIC, by activation of PPARa/PGC1a signaling pathway. These findings provide a therapeutic strategy for DIC through supplementation with AKK. Overall design: To investigate the cardioprotective effects of AKK on DIC and its potential mechanisms, we established a mouse model of doxorubicin-induced cardiotoxicity was established by intraperitoneally injecting C57BL/6 mice with doxorubicin at a dose of 5 mg/kg weekly for 4 consecutive weeks, resulting in a cumulative dose of 20 mg/kg. Colonization with Akkermansia muciniphila was achieved by administering 150 µl of the bacterial suspension at a concentration of 1*10^10 CFU/mL via gavage twice a week for 4 weeks. At the end of the experiments, Mouse hearts were rapidly harvested, rinsed in ice-cold phosphate-buffered saline (PBS), and flash-frozen in liquid nitrogen. The differentially expressed genes were analyzed by RNA-sequencing and clustering analyses.