Targeted Gut Microbiome Intervention to Reduce Anastomotic Leak in Colorectal Cancer Surgery: A Narrative Review and Potential Recommendations

Background/Objectives: Anastomotic leakage (AL) remains one of the most severe postoperative complications following colorectal surgery and is associated with increased morbidity, delayed adjuvant therapy, and impaired oncological outcomes in CRC patients. Increasing evidence suggests that alterations in the gut microbiome contribute to the pathogenesis of AL through effects on epithelial integrity, collagen metabolism, inflammatory pathways, and immune regulation. This review aimed to provide an updated overview of AL in CRC patients and to evaluate current evidence regarding the perioperative use of probiotics, prebiotics, and synbiotics as microbiome-modulating interventions in reducing AL after radical CRC surgery. Methods: A comprehensive literature review of randomized controlled trials (RCTs) investigating perioperative microbiome-targeted interventions in CRC patients undergoing colorectal surgery was conducted. Searches of PubMed, Embase, Cochrane Library, Scopus, and Clarivate databases identified 477 records, of which 21 RCTs met the inclusion criteria and were included in the final analysis. Results: Current evidence supports the role of probiotics in modulating postoperative immune and inflammatory responses. Four studies demonstrated a statistically significant reduction in AL incidence. Perioperative probiotic administration was additionally associated with lower rates of infectious complications, attenuation of systemic inflammatory responses, and earlier recovery of bowel function. Multi-strain formulations containing Lactobacillus and Bifidobacterium species appeared particularly promising. Overall, microbiome-targeted interventions were safe and well tolerated. However, treatment efficacy varied according to bacterial strain composition, dosage, and timing of administration. Conclusions: Perioperative microbiome modulation may contribute to restoration of gut microbial diversity and reduction in AL risk after radical CRC surgery. Multi-strain formulations containing Lactobacillus and Bifidobacterium species appear particularly promising. Nevertheless, further large-scale, standardized clinical trials are required before definitive recommendations can be established.