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Multicenter Study
. 2025 Dec 1;31(12):3247-3255.
doi: 10.1093/ibd/izaf147.

Isolated Anastomotic Ulcers Are Associated with a Higher Long-Term Risk for Postoperative Recurrence and a Differential Mucosa-Associated Microbiome Composition in Patients with Crohn's Disease Following Ileocolic Resection

Michiel Thomas Jan Bak  1   2   3 , Pablo Andres Olivera  1   2 , Cristian Hernandez-Rocha  1   2 , Krzysztof Borowski  1 , Williams Turpin  1   2   4 , Haim Leibovitzh  1   2 , Raquel Milgrom  1 , Joanne Stempak  1 , Mark Silverberg  1   2 , Sun-Ho Lee  1   2
Affiliations
Multicenter Study

Isolated Anastomotic Ulcers Are Associated with a Higher Long-Term Risk for Postoperative Recurrence and a Differential Mucosa-Associated Microbiome Composition in Patients with Crohn's Disease Following Ileocolic Resection

Michiel Thomas Jan Bak et al. Inflamm Bowel Dis. .

Abstract

Background: The clinical relevance and underlying mechanism of isolated anastomotic ulcers (IAUs) following ileocolic resection (ICR) in patients with Crohn's disease (CD) are poorly understood. This study aimed to assess the postoperative recurrence (POR) risk and the mucosa-associated microbiome composition in CD patients with or without IAUs among those with a healthy neo-terminal ileum (TI).

Methods: CD patients who underwent ICR and without any ulcerations in the neo-TI (SES-CD ≤2) at first postoperative ileocolonoscopy were identified from an ongoing prospective multicenter study. The primary study outcome was time to POR measured from the first postoperative ileocolonoscopy. Cox proportional hazard models were used to assess the association of IAUs with time to POR. The mucosa-associated microbiome at first ileocolonoscopy was assessed by sequencing the 16S rRNA gene using biopsies taken from both sides of the anastomosis.

Results: Sixty patients were included, of whom 27 patients had IAUs (45.0%) at first ileocolonoscopy. Median time to first postoperative ileocolonoscopy was 6.5 months (interquartile range [IQR] 5.3-8.1). During a median follow-up duration of 3.0 years (IQR 1.4-5.5) after first postoperative ileocolonoscopy, POR was observed in 53.3%. After adjustment for clinical risk factors, IAUs were independently associated with POR (adjusted hazard ratios 5.4; 95% CI 2.4-12.4; P < .001). At the ileal and colonic side of the anastomosis, a significantly higher abundance of Klebsiella was associated with IAUs (q < 0.05).

Conclusions: IAUs in CD patients with otherwise healthy neo-TI at first postoperative ileocolonoscopy are associated with long-term POR. In addition, a differential mucosa-associated microbiome composition was observed in patients with IAUs, specifically the proteobacteria Klebsiella, suggesting that putative taxa are related to these lesions. Further validation studies in larger cohorts, along with mechanistic studies, are still required.

Keywords: Crohn’s disease; anastomotic ulcers; microbiome; postoperative recurrence.

Plain language summary

This study assesses the clinical relevance and the microbial composition of patients with isolated anastomotic ulcers with otherwise healthy neo-terminal ileum in postoperative Crohn’s disease patients.

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Conflict of interest statement

None declared.

Figures

Figure 1.
Figure 1.
Representative image of isolated anastomotic ulcers during postoperative ileocolonoscopy.
Figure 2.
Figure 2.
Kaplan–Meier analysis of postoperative recurrence in patients with Crohn’s disease after ileocolic resection according to the presence of isolated anastomotic ulcers at first postoperative ileocolonoscopy.
Figure 3.
Figure 3.
Analysis of the mucosa-associated microbiota from the neo-terminal ileum (n = 41) comparing patients with and without isolated anastomotic ulcers. The figure includes alpha diversity metrics (A and B), beta diversity based on Bray–Curtis dissimilarity index (C), and differential relative abundance at the genus level (D).
Figure 4.
Figure 4.
Analysis of the mucosa-associated microbiota from the ascending colon (n = 36) comparing patients with and without isolated anastomotic ulcers. The figure includes alpha diversity metrics (A and B), beta diversity based on Bray–Curtis dissimilarity index (C), and differential relative abundance at the genus level (D).
See this image and copyright information in PMC

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