Association of the gut microbiome to colorectal anastomotic leakage: systematic review

Background Research into the gut microbiome and its possible association with anastomotic leakage after colorectal surgery has increased recently with the growing availability of sequencing techniques. There is a lack of systematic reviews addressing specifically microbiomic differences between patients with anastomotic leakage and patients with a successful anastomotic healing. The objective was to systematically review the current research on the microbiome and its effect on the risk of anastomotic leakage in colorectal cancer. Methods Pubmed/Medline, Cochrane, and Google scholar were searched on 14th February 2025, to identify relevant publications with the following inclusion criteria: colorectal surgery, microbiome sequencing data, anastomotic leakage as endpoint, and comparative groups. Exclusion criteria were studies conducted exclusively on animals, non-peer-reviewed studies, review articles, and unavailable full text. Alpha/beta diversity and microbiomic functional analyses were the focus of the results. Results From 112 studies, 11 studies including 551 patients were included: 143 patients with anastomotic leakage and 408 as controls. Alpha diversity differences were found in 7 of 11 studies—1 of 4 with preoperative sampling versus 6 of 7 studies with intra/postoperative sampling (P = 0.044). Beta diversity differences were found in 5 of 11 studies. Three studies reported on functional analyses, with one study demonstrating an association between methanogenesis and anastomotic leakage. Bacterial abundance was inconsistent across the studies. Three studies involving rodent models indicated a causal effect of the clinical microbiome. Conclusion Evidence implicates the gut microbiome as a factor associated with anastomotic leakage in colorectal cancer surgery, with three studies suggesting a causal relationship. There is a shortage of studies evaluating cross-species functional profiling. Optimal sampling should be performed during surgery.