Pre- and postoperative fecal microbiota and its association with complications after surgery in colon cancer patients

Dieuwertje Kok, Jannigje Kers, Hendriek Boshuizen, Niels Klaassen, Henk van Halteren, Flip Kruyt, Marjolein Smidt, Johannes de Wilt, Annemarie Boleij, Ellen Kampman, Erwin Zoetendal

Research output: Contribution to journalAbstractAcademic

Abstract

Introduction: Postoperative complications impact morbidity and mortality of colon cancer patients. Emerging evidence suggests that intestinal microbiota might play a critical role in the development of postoperative complications after gastrointestinal surgery. Here, we studied changes in fecal microbiota composition comparing samples collected before and after colon cancer surgery. Moreover, we examined whether the microbiota composition before surgery was associated with postoperative complications, and we explored potential determinants of the preoperative microbiota in colon cancer patients.
Methods: For this study, two fecal samples were provided by 78 patients with colon cancer. The first (preoperative) sample was collected shortly after diagnosis and before (median and interquartile (IQR) range of 4 (2-6) days) colon cancer surgery. The second (postoperative) sample was collected approximately 6 weeks (median and IQR of 42 (37-47) days) after surgery and before start of adjuvant chemotherapy (whenever applicable). Based on 16S ribosomal RNA gene amplicon sequencing, the fecal microbiota diversity and composition were determined. Preoperative microbiota composition of patients who developed postoperative complications in the 30 days following surgery (n=18, 23%) was compared to those who did not (n=60, 77%) using univariate and multivariate analyses. Explorative random forest analyses were conducted to identify predictors of complication status, with relative abundance of the core genera, sex, age, fecal calprotectin levels, dietary fiber intake, body mass index, smoking status, ASA classification, cancer stage and tumor location being considered as potential predictors.
Results: After surgery, microbial alpha diversity was reduced compared to the preoperative situation, whereas compositional changes over time only reached statistical significance for Lachnospiraceae NK4A136 and Coprococcus 1, which both decreased in relative abundance after surgery. Already before the start of surgery, relative abundance of the genera Bacteroides (10% vs 6%) and Lachnoclostridium (0.6% vs 0.2%) appeared to be higher in patients with complications versus those with uncomplicated recovery. In a prediction analysis, current smoking and relative abundance of Lachnoclostridium were identified as most profound predictors of complication status. Fecal calprotectin levels and current smoking status explained most (together 6%) of the overall variation in microbiota composition before surgery.
Conclusion: In this study, higher relative abundances of the genera Bacteroides and Lachnoclostridium before surgery were associated with postoperative complications in patients with colon cancer. Future studies should expand on the potential causal and pathogenic routes underlying these observations.
Original languageEnglish
Article number4380
JournalCancer Research
Volume83
Issue number7_Supplement
DOIs
Publication statusPublished - 4 Apr 2023

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