Patients with colon cancer often undergo surgery in which the affected piece of intestine is removed and the two remaining ends are reconnected, creating an anastomosis. Anastomotic leakage occurs in about 10% of cases and the reasons for that remain unclear. It has been shown that certain medications and bacterium can influence the healing of such an anastomosis, partly by affecting the intestine’s mucous layer. In addition, new techniques make it possible to view the anastomosis at the molecular level and thus to unravel the mystery of seam leakage. This is necessary to reduce the long-term burden of the disease and the risk of death after bowel surgery.