Perioperative changes in the microbiome during rectal cancer surgery: exploratory analysis of the National Institute for Health and Care Research (NIHR) IntAct trial

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BACKGROUND: The gut microbiome may influence postoperative outcomes after rectal cancer surgery, including anastomotic leak. However, perioperative microbiome dynamics and their association with outcomes remain poorly understood. The aim of this study was to characterize changes in the rectal microbiome in patients undergoing rectal cancer surgery within the National Institute for Health and Care Research (NIHR) IntAct trial. METHODS: Rectal swabs were collected at baseline, day of surgery, and postoperative day 3-5. DNA was extracted for 16S ribosomal RNA (rRNA) sequencing and collagenase-producing organisms were identified by culture. Associations between microbiome composition and clinical variables were analysed. RESULTS: A total of 202 patients were included (mean age 65 years; 69.8% male). At baseline, smoking status explained 3.2% of variation in beta-diversity (P = 0.046). On the day of surgery, beta-diversity was associated with hospital site (11.1%; P = 0.033), mechanical bowel preparation (2.6%; P = 0.024), and preoperative oral antibiotics (1.0%; P = 0.020). After surgery, hospital site (16.3%; P < 0.001), a defunctioning stoma (2.9%; P = 0.003), and preoperative oral antibiotics (1.6%; P = 0.006) influenced beta-diversity. Alpha-diversity decreased over time, with postoperative increases in Enterococcus and Prevotella. A defunctioning stoma was associated with lower alpha-diversity and increased Pseudomonas and Streptococcus. No significant difference in alpha- or beta-diversity was observed between patients with and without anastomotic leak, although subtle differences in taxa of low abundance were detected and 43.6% of postoperative samples demonstrated collagenase activity. CONCLUSION: This is the largest study to date describing perioperative microbiome changes in patients undergoing rectal cancer surgery. Measurable shifts in the microbiome were observed, with small differences between patients with and without anastomotic leak. Further research is needed to explore the clinical significance of these microbiome changes.

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