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.

Recent studies indicate that opportunistic gut bacteria contribute to the recurrence and chemoresistance in colorectal cancer (CRC); however, their fate after surgical resection remains poorly understood. This study investigated the longitudinal changes in these bacteria and assessed their potential persistence following CRC surgery. Forty fecal samples were collected from ten CRC patients at four timepoints: (1) pre-surgery (S); (2) one week (S1); (3) one month (S2); and (4) three months (S3) post-surgery. Fifteen other fecal samples were collected from healthy individuals as our study controls. Microbial profiling was performed using 16S rRNA gene sequencing, and quantitative PCR was applied to assess the changes in three opportunistic bacteria associated with CRC-associated. Our study revealed that Escherichia coli was significantly enriched in pre-surgical samples (S), while Enterococcus faecalis was predominant in the samples collected one-week after surgery (S1). All the assessed species showed a gradual post-surgical decline in relative abundance, suggesting they do not persist after resection. Additionally, there was a significant increase in relative abundance of beneficial bacterial signatures, including Akkermansia muciniphila, Bacteroides uniformis, Parabacteroides merdae, and Phascolarctobacterium faecium post-surgery, which implies a potential dysbiosis restoration. Our findings suggest that surgical resection gradually reduces the burden of opportunistic gut microbiota, thus gradually lowering the risk of recurrence and chemoresistance. Additionally, it may facilitate the restoration of beneficial taxa. Future studies should include extended follow-up periods to validate our findings and their correlation with clinical outcomes.