Exploring the Impact of Chemotherapy on the Emergence of Antibiotic Resistance in the Gut Microbiota of Colorectal Cancer Patients.

Abstract

With nearly half of colorectal cancer (CRC) patients diagnosed at advanced stages where surgery alone is insufficient, chemotherapy remains a cornerstone for this cancer treatment. To prevent infections and improve outcomes, antibiotics are often co-administered. However, chemotherapeutic interactions with the gut microbiota cause significant non-selective toxicity, affecting not only tumor and normal epithelial cells but also the gut microbiota. This toxicity triggers the bacterial SOS response and loss of microbial diversity, leading to bacterial mutations and dysbiosis. Consequently, pathogenic overgrowth and systemic infections increase, necessitating broad-spectrum antibiotics intervention. This review underscores how prolonged antibiotic use during chemotherapy, combined with chemotherapy-induced bacterial mutations, creates selective pressures that drive de novo antimicrobial resistance (AMR), allowing resistant bacteria to dominate the gut. This compromises the treatment efficacy and elevates the mortality risk. Restoring gut microbial diversity may mitigate chemotherapy-induced toxicity and improve therapeutic outcomes, and emerging strategies, such as fecal microbiota transplantation (FMT), probiotics, and prebiotics, show considerable promise. Given the global threat posed by antibiotic resistance to cancer treatment, prioritizing antimicrobial stewardship is essential for optimizing antibiotic use and preventing resistance in CRC patients undergoing chemotherapy. Future research should aim to minimize chemotherapy's impact on the gut microbiota and develop targeted interventions to restore microbial diversity affected during chemotherapy.