Sodium Butyrate Suppresses Colorectal Cancer Liver Metastasis

Background and objective: Colorectal cancer(CRC)liver metastasis(CLM)is the leading death cause of CRC patients,but there is no satisfied approach to treat CLM.Sodium butyrate(Na B),a major product of gut microbial fermentation,has antitumor effects and maybe used to treat CLM.Here,we investigated the efficacy of Na B in CLM mice.Methods and results: Male BALB/c mice intrasplenic injected CT26 cells to form CLM with/without Na B(350 mg/kg/day,i.g.)supplement.Healthy control mice received PBS or Na B.Microbiota of mice stool was analyzed using 16 S r RNA gene sequencing.The immune responses in mice liver were detected by Flow cytometry.Na B suppressed CLM in mice.In CLM mice,altered microbiota composition was characterized by increases of Firmicutes and Proteobacteria.Na B beneficially changed dysbiosis in CLM mice.KEGG analysis showed that Na B changed pathways related to immune system diseases and primary immunodeficiency in CLM mice.In addition,Na B decreased Tregs and increased NKT cells and Th17 cells,accordingly,decreased IL-10 and increased IL-17 secretion in CLM mice liver.Besides,Na B reduced the intake of CT26-derived exosomes in CLM mice liver and inhibited the formation of pre-metastatic niche in liver.Conclusions: Gut dysbiosis is related to CLM.Na B inhibits CLM by beneficially modulating gut microbiota and improving host immune response.Na B also inhibited the formation of pre-metastatic niche in liver.These findings demonstrate the therapeutic potential of Na B in CLM treatment.