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. 2025 Sep 2;112(9):znaf199.
doi: 10.1093/bjs/znaf199.

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

Jack A Helliwell  1 , Caroline H Chilton  1 , Caroline Young  2 , Emma V Clark  1 , Lyndsay Wilkinson  1 , Alba Fuentes Balaguer  1 , Daniel Bottomley  1 , Julie Croft  3 , Neil Corrigan  3 , Andrew Kirby  1 , Philip Quirke  1 , Deborah D Stocken  3 , David G Jayne  1 , Henry M Wood  1
Affiliations

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

Jack A Helliwell et al. Br J Surg. .

Abstract

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.

Plain language summary

The gut microbiome is the community of bacteria living in human intestines. These bacteria usually help keep humans healthy, but sometimes they cause illness. For people having surgery to remove rectal cancer, a serious complication is when the join between two parts of the bowel does not heal properly, known as anastomotic leak. Changes in the gut microbiome may contribute to this life-threatening problem. The aim of this study was to understand how the gut microbiome changes before, during, and after rectal cancer surgery, and whether these changes are related to postoperative outcomes, including anastomotic leak. A total of 202 patients having rectal cancer surgery at several NHS hospitals were studied. Samples from the rectum were collected before surgery, during surgery, and a few days after, and analysed to identify the types of bacteria present and their potential effects. The authors found that the mix of bacteria changed during treatment. Factors such as smoking, hospital location, bowel cleaning medication, and the use of a defunctioning stoma (a small opening to divert stool) affected the bacterial community. Many patients had bacteria that produce enzymes that may damage tissue. Although there were small differences in the microbiome between patients with and without leaks, no clear link was found. The study shows that the gut microbiome changes during rectal cancer surgery and is influenced by treatment choices. While small differences in those with leaks were found, more research is needed. Understanding these changes in bacteria could help to prevent complications after surgery.

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Figures

Fig. 1
Fig. 1
Microbial profiling of the study cohort a PERMANOVA (adonis2) analysis of Bray–Curtis beta-diversity across all metadata categories. R2 values represent the proportion of variation explained. ***P < 0.001. b PCoA plot of Bray–Curtis distances, with samples coloured by time point. c Shannon alpha-diversity by time point. Mann–Whitney U test P values are given. d Cumulative relative abundance of bacterial taxa across all samples, grouped by time point. PERMANOVA, permutational multivariate analysis of variance; PCoA, principle coordinate analysis.
Fig. 2
Fig. 2
Impact of a defunctioning stoma on the postoperative microbiome a Cumulative relative abundance of the most abundant bacterial taxa, stratified by the presence or absence of a defunctioning stoma. b PCoA plot of Bray–Curtis beta-diversity, grouped by time point and stoma status. c Shannon alpha-diversity of postoperative samples, stratified by stoma status. PCoA, principle coordinate analysis.
Fig. 3
Fig. 3
Postoperative spikes in specific taxa associated with a defunctioning stoma a Relative abundance of Pseudomonas across time points, stratified by stoma status. b Relative abundance of Streptococcus across time points, stratified by stoma status. c Proportion of most abundant genus in each postoperative sample, stratified by presence or absence of a defunctioning stoma.
Fig. 4
Fig. 4
Comparison of the postoperative microbiome by anastomotic leak status a Cumulative relative abundance of bacterial taxa in postoperative samples, stratified by presence or absence of anastomotic leak. b PCoA plot of Bray–Curtis beta-diversity, grouped by time point and anastomotic leak status. c Shannon alpha-diversity of postoperative samples, stratfied by anastomotic leak status. PCoA, principle coordinate analysis.
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