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P156 Microbiota diversity at time of surgery predict endoscopic recurrence in Crohn's disease: results of a prospective study of the REMIND group

Sokol H.*1, Brot L.2, Stefanescu C.3, Auzolle C.4, Barnich N.5, Buisson A.5, Fumery M.6, Nachury M.7, Treton X.3, Nancey S.8, Allez M.4, Seksik P.9 REMIND

1APHP INSERM INRA, APHP INSERM INRA, Paris, France 2University Pierre and Marie Curie, Paris, France 3APHP Beaujon, Clichy, France 4Saint Louis Hospital, APHP, Department Of Gastroenterology, Hospital Saint-louis, Paris, France 5University of Auvergne, Inserm U1071, Clermont-Ferrand, France 6Amiens Hospital, Amiens, France 7CHRU Lille, Department of Gastroenterology, Lille, France 8Lyon Hospital, Department of Gastroenterology and Hepatology, Lyon, France 9APHP St. Antoine Hospital, Department of Gastroenterology, Paris, France

Background

Operative resection in Crohn's disease (CD) is not curative. After ileocecal resection, endoscopic recurrence is frequently observed on the anastomosis and/or on the neo-terminal ileum. The aim of this study was to analyze the mucosa associated microbiota at time of surgery and to look for predictors of post-operative endoscopic recurrence within the microbiota.

Methods

This is a prospective study performed in 9 centers of the REMIND group, collecting clinical and biological data at time of surgery and of endoscopy (performed at 6 months). Bacterial composition of the ileal mucosa associated microbiota was analyzed at time of surgery in 146 patients with CD using 16S (MiSeq, Illumina) sequencing. The obtained sequences were analyzed using the Qiime pipeline to assess composition, alpha and beta diversity. Bacterial taxa associated with clinical parameters were identified using Multivariate association with Linear Models (MaAsLin) taking into account disease phenotype, clinical parameters and treatments.

Results

146 patients were included: 73 (50%) were male, median age at surgery was 32 years (IQR 26–42). Median disease duration was 6 years (IQR 2–12). 44 patients (30%) were active smoker at time of surgery. Thirty patients (21%) had a previous resection, and 35 patients (24%) had perianal lesions. At time of surgery, 67 patients (46%) had received anti-TNF therapy within the last 3 months. After surgery, 31 patients received thiopurines, and 52 patients received anti-TNF therapy. The microbiota was mainly composed of bacteria from the Firmicutes (mean 53%, range 0.3–99%), Proteobacteria (mean 36%, range 0.5–99%) and Bacteroidetes (mean 3%, range 0–52%) phyla. As expected, antibiotics treatment within one month before surgery had a dramatic impact on microbiota composition (Anosim, p<0.0001) and diversity (mean observed species: 302±17 vs 236±14, p=0.005). Taking into account only the patients who did not received antibiotics within a month before surgery, patients with endoscopic recurrence, defined by a Rutgeerts score ≥1, had a lower bacterial diversity at time of surgery compared to patients in endoscopic remission (mean observed species: 276±14 vs 365±45, p=0.015). This predictive value was lost in patients treated by anti-TNF postoperatively.

Conclusion

Ileal mucosa associated microbiota of CD patients at time of surgery is dominated by bacteria belonging to Firmicutes, Proteobacteria and Bacteroidetes phyla. Antibiotics induce major perturbations of the microbiota. Reduction in bacterial diversity at time of surgery is predictive of endoscopic recurrence but this predictive value is lost in patients treated by anti-TNF supporting the effectiveness of this post operative treatment.