Bifidobacterium Strain-Specific Enhances the Efficacy of Cancer Therapeutics in Tumor-Bearing Mice

SIMPLE SUMMARY: The efficacy of cancer therapeutics depends on several factors, including the tumor genome, epigenome, and transcriptome. In addition, the tumor microenvironment, which consists mainly of immune cells, can influence cancer treatment outcomes. Hence, effectively leveraging host immunity is an important aspect of cancer treatment strategies. The human gut microbiome is involved in the regulation of the immune responses and affects the efficacy of chemotherapeutic and immunotherapeutic agents, including oxaliplatin, cyclophosphamide, and immune checkpoint inhibitors. This study reveals an additional dimension to the Bifidobacterium strain-specific determination of anti-cancer therapeutic efficacy using flow cytometry and transcriptome analysis of bacterial strain-fed mice and bacterial whole transcriptome analysis. We hope that our work will contribute to leveraging the gut microbiome to improve anti-cancer therapies. ABSTRACT: Colorectal cancer (CRC) is among the leading causes of cancer-related death in the world. The development of CRC is associated with smoking, diet, and microbial exposure. Previous studies have shown that dysbiosis of the gut microbiome affects cancer development, because it leads to inflammation and genotoxicity. Supplementation with specific microbiota induces anti-tumor effects by enhancing of anti-tumor immunity. Here, we observed that supplementation with either of two B. breve strains reduces tumor growth in MC38 colon carcinoma-bearing mice. Interestingly, only one B. breve strain boosted the efficacy of cancer therapeutics, including oxaliplatin and PD-1 blockade. Extensive immune profiling and transcriptomic analysis revealed that the boosting B. breve strain augments lymphocyte-mediated anti-cancer immunity. Our results suggest that supplementation with B. breve strains could potentially be used as a strategy to enhance the efficacy of CRC therapeutics.