Bifidobacterium pseudocatenulatum capsular exopolysaccharide enhances systemic anti-tumour immunity in pre-clinical breast cancer.

Gut microbes have emerged as powerful regulators of cancer responses, with Bifidobacterium species and strains playing a key role in promoting anti-tumour immunity. While they represent promising candidates for cancer therapeutics, the specific underlying microbial mechanisms driving their efficacy remains poorly understood. In this study, we demonstrate the broad potential of Bifidobacterium species to inhibit breast cancer progression across multiple pre-clinical mouse models. We identify a novel strain, Bifidobacterium pseudocatenulatum 210, which induces systemic anti-tumour immunity and enhances responses to standard-of-care therapies via its cell surface capsular exopolysaccharide (EPS). 210 EPS remains predominantly gut local after oral administration and promotes dendritic cell activation, including preferential activation of small intestinal cDC1, leading to robust CD8+ T cell-mediated anti-tumour activity. Comparative structural analyses further support that EPS function is strain dependent. Our findings position Bifidobacterium EPS as a novel class of therapeutic compounds with significant potential for cancer treatment.