Probiotics Influence Gut Microbiota and Tumor Immune Microenvironment to Enhance Anti-Tumor Efficacy of Doxorubicin

Probiotics have been reported to influence the gut microbiota and immune system in various diseases. Now, the potential impacts of probiotics on tumor treatment still need to be investigated. In this study, three strains of probiotics, Bifidobacterium breve BBr60 (BBr60), Pediococcus pentosaceus PP06 (PP06), and Bifidobacterium longum subsp. longum BL21 (BL21) were investigated for their combination with chemotherapeutic drugs doxorubicin (DOX). Our study showed that PP06 and BL21 have good performance in gastric acid, bile salt, and intestinal fluid tolerance, antimicrobial activity to pathogenic Staphylococcus aureus, and adhesion to Caco-2 cells. Besides, the probiotics all exhibited antioxidant effect, especially BL21. In vitro cytotoxicity and in vivo animal studies revealed that probiotics used alone could not directly induce anti-tumor effects, but the combination of PP06/BL21 and DOX exhibits a higher inhibition rate than DOX alone, via recruitment and infiltration of immune cells in the tumor region. After 16S rRNA analysis of fecal samples from animal models, it was found that BL21 could increase the abundance of Akkermansia, which may also play a role in regulating the tumor microenvironment to improve immune response. In conclusion, BL21 and PP06 in this study could enhance the anti-tumor efficacy by influencing the gut microbiota and tumor immune microenvironment.