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DOP044 Relationship between microbiota and development of early postoperative Crohn's disease recurrence

Machiels K.*1, Pascal V.2, Sabino J.1, Santiago A.2, Campos D.2, Wolthuis A.3, De Buck van Overstraeten A.3, D'Hoore A.3, Van Assche G.1, Ferrante M.1, Rutgeerts P.1, Manichanh C.2, Vermeire S.1

1University Hospitals Leuven, KU Leuven, Translational Research Center for Gastrointestinal Disorders (TARGID), Leuven, Belgium 2Vall d'Hebron Research Institute, Barcelona, Spain 3University Hospitals Leuven, Department of Abdominal Surgery, Leuven, Belgium

Background

Dysbiosis of the intestinal microbiota is implicated in Crohn's disease (CD) and may play an important role in triggering postoperative disease recurrence (POR).

We hypothesized that the fecal microbial recolonization process after ileocecal resection differs between patients developing recurrence and patients remaining in remission, and further aimed to identify other factors influencing the microbial composition.

Methods

Fecal samples from 54 CD patients undergoing ileocecal resection were prospectively collected before surgery and at month 1, 3 and 6 after surgery. POR - defined by a modified Rutgeerts score ≥i2b on endoscopy was assessed at month 6. The microbiota was evaluated by 16S rDNA sequencing using an Illumina MiSeq platform. Calculation of alpha and beta diversity and statistical analysis were performed in QIIME.

Results

Patients developing early POR (N=23) harbored more Coriobacteriaceae, Corynebacteriaceae and Micrococcaceae in their faecal samples before surgery, than patients without recurrence (N=31) (p<0.04). During the first 3 months postoperatively, no significant taxonomic differences were observed between both patient groups. At month 6, recurrence patients had a higher relative abundance of Fusobacteria (FDR=0.09). The impact of resection on the fecal microbiome was shown by an increase of Negativicutes (FDR=0.02) and reduction of Bifidobacteriales (FDR=0.04) in all CD patients whereas recurrence patients additionally were marked by an increase of Fusobacteria (FDR=0.03) and decrease of Faecalibacterium (p=0.04).

Smoking (N=16) was not associated with early POR in this cohort, but smoking did impact on the fecal microbiota. Alpha diversity was significantly reduced in active smokers at baseline (p=0.028), month 3 (p=0.016) and month 6 (p=0.023) after surgery. In general, smokers were characterized by an enrichment of Veillonellaceae (FDR=0.09) and reduction of Ruminococcaceae (FDR=0.005) and Lachnospiraceae (FDR=0.03). Within these families, the relative abundance of essential types of butyrate and other short-chain fatty acids-producing bacteria such as Faecalibacterium, Roseburia, Dorea, Coprococcus, Blautia and Ruminococcus were depleted.

Conclusion

Ileocecal resection has an impact on the fecal microbiota composition which mostly affects members of Negativicutes and Bifidobacteriales. The microbial differences between patients developing recurrence and patients remaining in remission are minor during the first 3 months whereas early recurrence at month 6 was mainly associated with an enrichment of Fusobacteria. Although smoking was not associated with early POR, it did show a significant impact on the microbial composition which might have potential implications at later stages of the disease.