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

Abstract 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.