Gut Microbiota Modulation of Efficacy and Toxicity of Cancer Chemotherapy and Immunotherapy

Accumulating evidence supports not only the functional role of the gut microbiome in cancer development and progres-sion but also its role in defining the efficacy and toxicity of chemotherapeutic agents (5-fluorouracil, cyclophosphamide, irinotecan, oxaliplatin, gemcitabine, methotrexate) and immunotherapeutic compounds (anti-programmed death-ligand 1/anti-programmed cell death protein 1 and anti-cytotoxic T-lymphocyte-associated antigen 4). This evidence is supported in numerous in vitro, animal, and clinical studies that highlight the importance of microbial mechanisms in defining therapeutic responses. The micro -biome therefore shapes oncologic outcomes and is now being leveraged for the development of novel personalized therapeutic approaches in cancer treatment. However, if the microbiome is to be successfully translated into next -generation oncologic treatments, a new multimodal model of the oncomicrobiome must be conceptualized that in-corporates gut microbial cometabolism of pharmacologic agents into cancer care. The objective of this review is therefore to outline the current knowledge of oncologic pharmacomicrobiomics and to describe how the multi -parametric functions of the gut microbiome influence treatment response across cancer types. The secondary objective is to propose innovative approaches for modu-lating the gut microbiome in clinical environments that improve therapy efficacy and diminish toxic effects derived from antineoplastic agents for patient benefit.

Automated summary

Accumulating evidence supports the important role of the gut microbiome in cancer development and progression, as well as its influence on the efficacy and toxicity of cancer treatments. The microbiome is now being utilized to develop personalized therapeutic approaches in cancer treatment. However, the development of a new model that incorporates gut microbial cometabolism of drugs is necessary for the successful translation of the microbiome into next-generation oncologic treatments. The objective of this review is to outline the current knowledge of oncologic pharmacomicrobiomics and propose innovative approaches to modulate the gut microbiome for improved therapy efficacy and reduced toxic effects.