Gut Microbiota and Anastomotic Leakage in Colorectal Surgery: A Systematic Review

Abstract Background Anastomotic leakage (AL) is a serious and potentially life-threatening complication following colorectal surgery, associated with increased morbidity, mortality, and impaired oncologic outcomes. Growing evidence suggests that the gut microbiome influences anastomotic healing and may represent a modifiable risk factor for AL. However, existing studies report inconsistent results, and no systematic review has yet comprehensively evaluated the association between gut microbiota and AL in clinical and experimental settings. Aims This study aims to systematically review the existing literature on the relationship between gut microbiota composition and the incidence of colorectal anastomotic leakage. Primary outcome was the incidence of anastomotic leakage. Secondary outcomes included microbial diversity, taxonomic signatures, histological or molecular markers of healing, and effects of microbiota-targeted interventions. Methods A systematic search of Medline, Embase, Web of Science, and the Cochrane Library was performed by three reviewers from inception to July 2025 following PRISMA 2020 guidelines. Randomized trials, cohort, and case-control studies assessing associations between AL and gut microbiota were included. Risk of bias was evaluated using ROBINS-I for non-randomized clinical studies and SYRCLE for preclinical studies. Results Twelve studies were included. AL was consistently associated with reduced microbial diversity and enrichment of pro-inflammatory or collagen-degrading taxa. In contrast, protective commensal bacteria were reduced. Several studies identified perioperative microbial signatures predictive of anastomotic healing or leakage. The C-seal device appeared to reduce microbiota differences between AL and non-AL patients. Conclusion Alterations in the gut microbiome are associated with impaired colorectal anastomotic healing. These findings support the role of microbiome-based risk stratification and perioperative interventions to reduce AL. A better understanding of microbial contributions may prompt a re-evaluation of current perioperative protocols, balancing infection prevention with preservation of beneficial commensal bacteria. Ultimately, microbiome-targeted therapies could emerge as adjuncts to enhance anastomotic integrity and reduce postoperative morbidity.For image description, please refer to the figure legend and surrounding text.