Microbiome recovery following colorectal surgery and antibiotic exposure in mice is dependent on diet and has a major influence on anastomotic healing: a longitudinal 16S rRNA analysis

Background: Previous work has indicated that major compositional and functional changes in the colon microbiota develop following removal of segment of the colon (resection) and its reconnection (anastomosis). Effect of microbiota on anastomotic healing becomes well evident and demonstrated that collagenolytic bacteria (i.e., Enterococcus faecalis) impair healing leading to anastomotic leak with undesirable consequences. Among the patients’ physiological factors associated with post-operative leakage is obesity. Here we performed longitudinal analyses of colonic microbiota during the healing period after colon resection in mice to address if an obesity-related diet influences the post-operative colonic microbiome composition. Results: Pre-operatively, the colonic microbiota of PUFA- fed mice was characterized by lower diversity, a significant shift in composition (beta-diversity), and an alteration in the Firmicutes:Bacteroidetes ratio in favor of increased Firmicutes. Longitudinal analysis of expelled stool in PUFA-fed mice demonstrated a bloom of Enterococcus at the second post-operative day (POD) 2-4 , reaching a relative abundance of 90%, whereas in Chow- fed mice a modest 15% increase was observed. Eventually Enterococcus disappeared in Chow-fed mice at POD5, however it persisted in expelled stool in PUFA fed mice and was observed at high density in the colonic tissues of PUFA-fed mice sacrificed on POD24-28. The microbiota of Chow-fed mice was restored to its preoperative composition by POD14-18 however microbiota remained persistently disrupted in PUFA-fed mice. Collagenolytic Enterococcus, a phenotype previously demonstrated to be causative of anastomotic disruption, predominated in the anastomotic tissues of PUFA-fed mice and was accompanied by other potentially collagenolytic bacteria including Proteus and Serratia. PUFA, but not chow-fed mice demonstrated significantly impaired anastomotic healing in this model (p<0.001). Conclusion. Pre-operative exposure of the colonic microbiota to the selective pressures of high fat/low fiber Western-type diet, preferable diet of obese human, has a major influence on the post-operative colonic microbiota characterized by a tremendous increase of Enterococcus associated with impaired anastomotic healing.