A high-fat, Western diet (WD) is a risk factor for post-resection tumour recurrence in colorectal cancer (CRC). A new study investigates how this diet promotes tumour recurrence in mice undergoing colorectal resection, and suggests a role for collagenolytic bacteria at the site of anastomosis.

“Intestinal surgery induces significant changes in the gut bacterial composition and we hypothesized that these changes could influence cancer cells to migrate through a healing reconnection to cause a recurrence,” explains co-senior author Benjamin Shogan. “Thus, we wanted to create a model that would allow us to tease out the influence of bacteria on CRC recurrence, in the hope of decreasing recurrence rates.”

Immunocompetent male mice were fed either a WD or a standard chow diet for 4 weeks before colorectal resection surgery. Previous work had demonstrated that anastomoses can attract collagenase-producing microbiota such as Enterococcus faecalis, which might then render these tissues susceptible to tumour formation. Thus, after surgery, all mice received enemas of E. faecalis and colon carcinoma cells before colons were removed and analysed 21 days after surgery. Some mice also received prophylactic antibiotics or a collagenase-suppressing compound (Pi-PEG).

Of the mice exposed to E. faecalis, 88% fed a WD had CRC tumour formation compared with 30% fed the standard diet. Tumour formation in anastomotic tissues correlated with the presence of E. faecalis and Proteus mirabilis, another collagenolytic bacterial species, but no significant difference was observed between mice fed a WD with or without antibiotics. Although broad antibiotic treatment eliminated the collagenolytic species, the dysbiosis resulted in the emergence of a collagenolytic fungal species. However, administration of Pi-PEG reduced collagenolytic bacteria and tumour formation while maintaining microbial diversity.

anastomoses can attract collagenase-producing microbiota

“We found that in certain environmental conditions, such as a preoperative high-fat Western diet, and intestinal colonization with collagenase-producing bacteria, tumour cells are promoted to escape the intraluminal environment to form a tumour,” concludes Shogan. “We are now trying to understand how collagenolytic organisms promote tumour recurrence and develop novel strategies to prevent it.”