Colorectal anastomotic leakage after colon cancer surgery remains a serious complication that increases mortality and worsens treatment outcomes despite advances in surgical technique[1]. New findings show that anastomotic failure is not just a technical problem, but a biological process in which the gut microbiome regulates inflammation, tissue healing, and gut barrier integrity[1]. A healthy and diverse gut microbiome promotes anastomotic healing through short-chain fatty acid production and immune system enhancement[1]. Conversely, certain bacteria such as Enterococcus faecalis, Fusobacterium nucleatum, and Alistipes onderdonkii, along with fungal and viral changes, are associated with tissue damage and excessive inflammation[1]. The article examines gut microbiome-based biomarkers that could help predict the risk of leakage before and shortly after surgery[1]. Perioperative microbiome-targeted strategies include dietary changes, bacterial supplementation, selective decontamination, and fecal microbiota transplantation, although their routine use in practice is still limited[1]. The article emphasizes that anastomosis leakage should be understood as an interaction between the patient and his microbiome, which opens up new possibilities for the prevention of this complication[1].