Microbiome and Cancer: Exploring the Influence of Gut Microbiota on Immunotherapy Efficacy and Toxicity

The gut microbiome is a complex ecosystem of trillions of microorganisms that are essential to help regulate the human immune system, and its role in cancer treatment outcomes has become recognized as particularly relevant for immunotherapy. The landscape of cancers such as melanoma, lung or renal cancer has dramatically changed since immune checkpoint inhibitors (ICIs) including anti-PD-1, anti-PD-L1 and anti CTLA-4 therapies emerged. Nevertheless, response rates are limited and challenges remain regarding immune-related adverse events (irAEs). Recent studies have compellingly shown ICIs efficacy and toxicity to be influenced by the composition of an individual’s gut microbiota. Several bacterial taxa, including Akkermansia muciniphila, Faecalibacterium and Bifidobacterium are associated with better response to therapy whereas dysbiosis can contribute both treatment failure and irAEs. The review examines the mechanisms of gut microbiota in affecting immune responses and discusses how translating these findings might be used to leverage immunotherapy, as well describing potential actions already available (probiotic/ pre/pro-symbiotics/ FMT) for improving efficacy; also, it presents implications on clinical perspectives using microbiome-based strategies driving personalized cancer care. Given the critical role of gut-cancer-immune axis in cancer immunotherapy, a more comprehensive understanding on its mechanisms could open new avenues for improving patient outcomes and reducing toxicity.