Bifidobacterium bifidum strains synergize with immune checkpoint inhibitors to reduce tumor burden in mice

The gut microbiome can influence the development of tumors and the efficacy of cancer therapeutics1-5; however, the multi-omic characteristics of anti-tumor bacterial strains have not been fully elucidated. In this study, we integrated metagenomics, genomics, and transcriptomics of bacteria, and analyses of mouse intestinal transcriptome and serum metabolome to reveal an additional mechanism by which bacteria determine the efficacy of cancer therapeutics. In gut microbiome analyses of 96 non-small cell lung cancer (NSCLC) patients, Bifidobacterium bifidum was abundant in patients responsive to therapy. However, when we treated syngeneic mice tumors with commercial strains of B. bifidum to establish relevance for potential therapeutic uses, only specific B. bifidum strains reduced tumor burden synergistically with PD-1 blockade or oxaliplatin treatment by eliciting an anti-tumor host immune response. In mice, these strains induced tuning of immunological background by potentiating the production of interferon-gamma, likely through the enhanced biosynthesis of immune stimulating molecules and metabolites.