Abstract
BackgroundThe standard of care of colorectal cancer (CRC) management consists of surgical resection of the colon or rectum, followed by a reconnection, or ‘anastomosis’, of the remaining bowel ends to re-establish gastrointestinal continuity. Up to 30% of patients may present poor healing of the anastomosis, and anastomotic leak (AL), a major complication that increases mortality and morbidity after surgery. Our objective is to investigate the possible role of the gut microbiome in anastomotic healing in patients with CRC.MethodsPreoperative fecal samples were collected from CRC patients undergoing surgery. The gut microbiota of patients with AL and of others that presented optimal healing were analyzed and compared using the Anchor pipeline. Fecal microbiota transplantation (FMT) was performed in mice using preoperative fecal samples from CRC patients with and without AL. Mice were then subjected to colonic surgery using a colonic anastomosis model. After 6 days, anastomotic healing and the gut barrier were assessed. The gut microbiota composition was compared as well to detect potential differences between the groups of mice transplanted from donors with and without AL.ResultsMice colonized by FMT with the microbiota of donors with AL displayed macroscopically poorer healing of the colonic anastomosis and a higher bacterial translocation to the spleen, suggestive of a weaker gut barrier after surgery. The anastomotic wounds of mice receiving the microbiota of AL donors displayed lower concentrations of collagen and fibronectin and higher inflammatory cytokines, indicating poor extracellular matrix formation after surgery. This was accompanied by a higher expression of collagenolytic enzymes, indicative of collagen degradation at the wound site. The beta diversity of the gut microbiota was significantly different between mice receiving the microbiota of donors with and without AL. Several bacterial species were differentially abundant between the two groups and were associated with the healing process.ConclusionsThe preoperative gut microbiota in CRC patients with poor postoperative healing induces poor healing in mice and a weaker gut barrier after surgery. These results suggest a causal role for the gut microbiota in colonic healing after surgery in patients with CRC.