Gut Microbiota and Microbial Metabolites in the Regulation of Chemotherapeutic Resistance

Resistance to chemotherapy continues to be a significant challenge for cancer treatment and a contributing factor to treatment failures and tumor progression. Recently, the gut microbiome has emerged as an important modulator of the response to chemotherapy. Numerous pre-clinical and clinical studies have demonstrated a direct association between gut microbiota composition and therapy effectiveness in many cancer types, such as colorectal, breast, pancreatic, gastric, and lung cancers, melanoma, and hematological cancers. Gut microbiota effectively regulate the efficiency of chemotherapeutic agents in various ways, either by biotransformation of chemotherapeutic agents or modulation of host immunity. In addition, microbial metabolites such as short-chain fatty acids, secondary bile acids, and tryptophan metabolites are also involved in the regulation of chemotherapy response through modulating apoptosis, immunity, and epithelial–mesenchymal transition. Finally, dysbiosis induced by chemotherapy and antibiotics has also been reported to reduce the effectiveness of therapy. This review will emphasize the ways in which gut microbiota can modulate chemotherapeutic response and induce chemoresistance. Understanding the interactions between chemotherapeutic drugs and the gut microbiota can help to enhance the efficiency of chemotherapy and find more appropriate personalized treatments.