Kenneth Mutebi John, Wu Chin-Chia, Fang Chuan-Yin, Hsu Tsui-Kang, Lin I-Ching, Huang Shih-Wei, Chiu Yi-Chou, Hsu Bing-Mu
Department of Earth and Environmental Sciences, National Chung Cheng University, Chiayi 621, Taiwan.
Doctoral Program in Science, Technology, Environment and Mathematics, National Chung Cheng University, Chiayi 621, Taiwan.
Antibiotics (Basel). 2025 Mar 5;14(3):264. doi: 10.3390/antibiotics14030264.
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.
近一半的结直肠癌（CRC）患者在确诊时已处于晚期，仅靠手术治疗并不足够，化疗仍是这种癌症治疗的基石。为预防感染并改善治疗效果，抗生素常与化疗联合使用。然而，化疗药物与肠道微生物群的相互作用会导致显著的非选择性毒性，不仅影响肿瘤细胞和正常上皮细胞，还会影响肠道微生物群。这种毒性会引发细菌的SOS反应并导致微生物多样性丧失，进而导致细菌突变和生态失调。因此，致病性细菌过度生长和全身感染增加，需要使用广谱抗生素进行干预。本综述强调，化疗期间长期使用抗生素，再加上化疗诱导的细菌突变，会产生选择性压力，促使新的抗菌药物耐药性（AMR）出现，使耐药细菌在肠道中占主导地位。这会损害治疗效果并增加死亡风险。恢复肠道微生物多样性可能会减轻化疗诱导的毒性并改善治疗效果，而粪便微生物群移植（FMT）、益生菌和益生元等新兴策略显示出了巨大的潜力。鉴于抗生素耐药性对癌症治疗构成的全球威胁，优先进行抗菌药物管理对于优化抗生素使用和预防接受化疗的CRC患者产生耐药性至关重要。未来的研究应致力于尽量减少化疗对肠道微生物群的影响，并开发有针对性的干预措施，以恢复化疗期间受影响的微生物多样性。
