Impact of castalagin prebiotic on the gut microbiota and immune response to anti-PD-1 therapy

The gut microbiome has emerged as a hallmark of cancer and a key contributor to influencing clinical outcomes with immune checkpoint inhibitors (ICI) in various cancers. Metagenomics sequencing studies coupled with experiments in germ-free mice have revealed that the gut microbiota bacteria including Akkermansia muciniphila, Ruminococcus and Alistipes were associated with cytotoxic T Helper, CD8+ T cell infiltration, which correlated with improved ICI response. Several clinical studies now focus on modulating the microbiome to enhance the immune response and improve outcomes with ICI, including proof-of-principle fecal microbiota transplantation (FMT) clinical trials in melanoma. Our group recently unravelled the therapeutic potential of castalagin, a prebiotic that beneficially increased anti-PD-1 response in murine models, opening novel therapeutic avenues for patients with cancer.