Gut microbiome influences on anastomotic leak and recurrence rates following colorectal cancer surgery

Abstract

Background: The pathogenesis of colorectal cancer recurrence after a curative resection remains poorly understood. A yet-to-be accounted for variable is the composition and function of the microbiome adjacent to the tumour and its influence on the margins of resection following surgery.

Methods: PubMed was searched for historical as well as current manuscripts dated between 1970 and 2017 using the following keywords: 'colorectal cancer recurrence', 'microbiome', 'anastomotic leak', 'anastomotic failure' and 'mechanical bowel preparation'.

Results: There is a substantial and growing body of literature to demonstrate the various mechanisms by which environmental factors act on the microbiome to alter its composition and function with the net result of adversely affecting oncological outcomes following surgery. Some of these environmental factors include diet, antibiotic use, the methods used to prepare the colon for surgery and the physiological stress of the operation itself.

Conclusion: Interrogating the intestinal microbiome using next-generation sequencing technology has the potential to influence cancer outcomes following colonic resection.

© 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.

Figures

Fig. 1

Hypothesized mechanism of colorectal cancer recurrence following surgical resection. Across the continuum of care to treat colorectal cancer (preoperative chemoradiotherapy, antibiotics, surgical resection), a unique environmental context is created that promotes colonization by collagenase-producing microbes (Enterococcus faecalis) followed by implantation of cancer cells, which are shed continuously both during and after surgery. High collagenase-producing microbes may activate local macrophages such that anastomotic healing is impaired in a manner that promotes shed cancer cells to implant and migrate to extramucosal sites, leading to local tumour recurrence. MMP, matrix metalloproteinase

Fig. 2

Theoretical perioperative microbiome disruption. As the body undergoes various stressors, such as antibacterial and purgative preoperative preparation, as well as surgical manipulation, the microbiome changes accordingly. In aggregate, these factors provide stress to the microbiome with a reduction in commensal bacteria and a proliferation of low-abundance γ proteobacteria that cause infection. The point of susceptibility to infection (*) marks a theoretical time point at which the virulence activation of pathogenic bacteria and the suppression of healing-promoting species would make the patient most likely to become infected. It is a vulnerable period that determines whether future postoperative recovery is complicated by microbial dissemination. FMT, faecal microbiota transplant; PUFA, polyunsaturated fatty acids