The composition of the intestinal microbiome appears to be a major contributor to the occurrence of postoperative complications including SSI, anastomotic leak, POI, and C. difficile infection. However, the impact of important perioperative factors that are known to shape its composition have not been described. This study showed that while MBP alone does change the composition of the microbiome, the magnitude of this shift is small, and the gut microbiome composition reverts to baseline by ten days following colonoscopy. In contrast, patients who received SBP displayed acute shifts of greater magnitude, requiring at least 30 days to return to a composition similar to baseline. Colorectal surgery with or without bowel resection did not appear to significantly impact the gut microbiome among surgical patients, as changes were observed in all such patients, independent from underlying disease or type of colorectal resection. While the aim of our study was to assess perioperative shifts in the microbiota, our sample sizes and patient heterogeneity exclude specific conclusions related to type or surgery, disease, or patient outcome. In this study, MBP with OA was the single most influential factor in shaping the composition of the gut microbiome acutely and longitudinally following colon and rectal surgery.
These observations build on our previous work, that perioperative antibiotics most significantly impact acute postoperative changes in the microbiome, to a greater extent than caloric restriction or gastric resection, following vertical sleeve gastrectomy 12. The impact of SBP is demonstrated longitudinally in the gut microbial composition with potential implications for postoperative complications in patients undergoing colon and rectal surgery. Communities from surgery patients showed a directional shift away from preoperative assemblages, with greater abundances of Enterococcus, Lactococcus, and Streptococcus. These changes are noteworthy as they may be associated with adverse post-operative outcomes. For example, Enterococcus has been mechanistically linked to the development of anastomotic leak via the production of matrix metalloproteinase 9, which degrades collagen leading to tissue breakdown 8. Enterococcus and Streptococcus are also potent bacteriocin and lactic acid producing bacteria 13,14, and may be general markers for dysbiotic stress in the clinical setting. These bacteria dominate the microbiota composition, disrupt the gut barrier, and are associated with the subsequent development of bacteremia in patients who received antibiotics for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients who undergo allo-HSCT have shown to develop markedly reduced microbial diversity which is an independent predictor of mortality 15. In fact, patients who are dominated by these particular organisms are at highest risk for bloodstream infections during allo-HCST 16. Overall, our data are consistent with many of the deleterious changes observed in patients undergoing allo-HSCT.
We also observed a significant reduction in the relative abundance of critical genera including Bacteroides, Faecalibacterium, and Roseburia in surgery patients compared to colonoscopy patients. Anastomotic leak has been associated with a relative paucity of Faecalibacterium 17. Abundances of both Faecalibacterium and Roseburia genera strongly correlate with microbial diversity, and their reduction has been suggested in the pathogenesis of ulcerative colitis 17–19. Interestingly, we noted correlations between SCFA and butyrate producing Roseburia and Blautia among samples collected in the surgical arm, while Faecalibacterium negatively correlated with SCFA concentrations among patients undergoing colonoscopy. These results suggest that typically cited butyrate producers may act in a compensatory manner following surgery to promote healing, while normal microbial communities shift this function to members of Bacteroidetes (e.g., Alistipes), as observed in the colonoscopy group. This suggestion further highlights the need to explore microbial community interactions to better assess the role of the microbiome in postoperative healing and complications. It is noteworthy that fecal levels of butyric acid and valeric acid precipitously declined following surgery. Dysbiotic microbiota with depleted SCFA results in dysregulated immune function propagating intestinal and systemic inflammation and colitis impeding wound healing 20. This likely has greater significance in the immediate postoperative phase in which colonic healing is actively taking place at a time when butyric acid and valeric acid are at their nadir levels.
Our singular anastomotic leak patient provides an effective case study for the effects of SBP. Preoperatively, the patient’s microbial composition was similar to that of the surgical cohort, and while the microbial composition shifted with MBP plus OA, the anastomotic leak patient’s composition was overwhelmingly dominated by Streptococcus. Notably, postoperative IgA levels were 16-fold higher in this patient compared to the perioperative sample, suggesting a significant and concomitant increase in gut inflammation. This patient displayed significant shifts in composition after each surgery, highlighting the impacts of SBP and perioperative IV antibiotics on the intestinal microbiome. This patient also highlights a potentially deleterious impact of SBP, and perhaps instead of protecting the patient, providing an ecologic advantage for streptococcal propagation of inflammation and anastomotic breakdown.
Our study does have important weaknesses, including the lack of mucosal microbiota, which may be different from the luminal microbiome reflected in stool 21,22. Secondly, a larger cohort of patients is required to verify our observations. This would also enable the identification of more specific changes in the microbiome that correlate with postoperative outcomes. Additionally, we included patients undergoing a variety of different types of operations. While this broad inclusion makes it difficult to identify a relationship between SBP and compositional changes in the gut microbiome, it does strengthen one of the findings of this study – that type of colorectal surgery with or without bowel resection impacts the composition of the microbiome to a lesser extent than the profound impact of SBP. Also, while we did not observe a change in fecal IgA or calprotectin, we did identify a strong inverse correlation between IgA levels and alpha diversity, which is consistent with previous reports 23. It remains possible that IgA levels and fecal calprotectin do change with postoperative shifts in the microbiome, but a larger cohort is required to investigate potential relationships. Future studies with more patients are required to answer these questions which were beyond the scope of this study.
In conclusion, this study showed that SBP with perioperative IV antibiotics has a significant impact on the postoperative composition of the gut microbiome following colon and rectal surgery. Although SBP represents a critical tool that has been associated with less intestinal microbial-driven complications, this mechanism of action via the microbiome remains unclear and requires further investigation. While effective, SBP remains a shotgun approach that does not consider the patient’s native microbiome, thus hindering a personalized approach to optimizing patient outcomes following surgery. The eradication of the intestinal microbiome acutely following surgery may represent a unique opportunity to intervene and sets forth a premise for the re-introduction of critical commensal bacteria that contribute to gut health and recovery at a time when the patient needs it most.