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P714 Intestinal microbial signature predicts postoperative Crohn's disease recurrence following ileocaecal resection with ileocolonic anastomosis

K. Machiels*1, W. Vanhove1, J. Sabino1, M. Joossens2, 3, 4, I. Arijs1, I. Terrasson5, V. Ballet1, G. Van Assche1, J. Verhaegen6, A. Wolthuis5, A. de Buck van Overstraeten5, A. D'Hoore5, M. Ferrante1, P. Rutgeerts1, S. Vermeire1

1University Hospitals Leuven, KU Leuven, Translational Research Center for Gastrointestinal Disorders (TARGID), Leuven, Belgium, 2VUB, Department of Microbiology, Brussels, Belgium, 3KU Leuven, Department of Microbiology and Immunology, Leuven, Belgium, 4VIB, Center for the Biology of Disease, Leuven, Belgium, 5University Hospitals Leuven, Department of Abdominal Surgery, Leuven, Belgium, 6KU Leuven, Department of Clinical Microbiology, Leuven, Belgium

Background

Dysbiosis of the intestinal microbiota has been described in Crohn's disease (CD) and may play an important role in the early events triggering postoperative disease recurrence. We hypothesized that microbiota are altered in patients with early postoperative endoscopic recurrence (ER) and evaluated if the risk for postoperative ER can be predicted based on differences in the fecal microbial composition before surgery.

Methods

Fecal samples from 30 CD patients (median age 46 years, 16 male) undergoing ileocaecal resection with ileocolonic anastomosis were prospectively collected before surgery and at month 1, 3 and 6 after surgery. Postoperative ER - defined by a Rutgeerts score ≥i2 - was assessed at month 6. The predominant microbiota was studied using denaturing gradient gel electrophoresis (DGGE) and bands of interest were sequenced. Partial Least Squares Discriminant Analysis (PLS-DA) was used to cluster the microbial profiles using Unscrambler. Statistical analysis was performed using SPSS and R software.

Results

Based on the preoperative microbial profiles, two clusters of patients were identified: those developing early ER (N=12) and patients without ER (N=18) (Figure 1).

 

ECCOJC jju027 P714 F0001

“Figure 1: PLS-DA shows a clustering of patients with ER (N=12) versus patients in remission (N=18) at month 6, based on preoperative microbial profiles.”

Before surgery, a reduction of the Lachnospiraceae family (p=0.05) and Clostridium XVIII genus (p=0.032) was seen in the predominant microbiota of patients developing early postoperative ER whereas 3 members of Clostridium XIVa genus (p=0.073), Veillonellaceae family (p=0.028) and Bifidobacterium genus (p=0.01) were higher in patients with ER compared to patients without ER.

A score combining these five bacterial risk factors was calculated and showed an area under the curve of 0.87 (95% CI, 0.76–0.99). The occurrence of two or more risk factors had a sensitivity, specificity, positive predictive value, and negative predictive value of 100%, 56%, 60% and 100% respectively. At the time of postoperative endoscopy, we observed an overrepresentation of Lactobacillus genus (p=0.003) and Ruminococcus gauvreauii (p=0.01) in the patients with ER.

 

Conclusion

An overrepresentation of Clostridium XIVa spp., Veillonellaceae, Bifidobacteria and a lower abundance of Lachnospiraceae and Clostridium XVIII spp. in the predominant profile of preoperative fecal samples is associated with a higher risk to develop postoperative ER following ileocaecal resection. At the time of postoperative endoscopy, the predominant microbiota from patients with ER also differs from patients without recurrence, with as most prominent players lactobacilli and R. gauvreauii.