Article Text
Abstract
Objective We used the postoperative recurrence model to better understand the role of adherent and invasive Escherichia coli (AIEC) bacteria in Crohn’s disease (CD), taking advantage of a well-characterised postoperative cohort.
Design From a prospective, multicentre cohort of operated patients with CD, AIEC identification was performed within the surgical specimen (M0) (N=181 patients) and the neoterminal ileum (n=119 patients/181) during colonoscopy performed 6 months after surgery (M6). Endoscopic postoperative recurrence was graded using Rutgeerts’ index. The mucosa-associated microbiota was analysed by 16S sequencing at M0 and M6. Relative risks or ORs were adjusted on potential confounders.
Results AIEC prevalence was twofold higher within the neoterminal ileum at M6 (30.3%) than within the surgical specimen (14.9%) (p<0.001). AIEC within the neoterminal ileum at M6 was associated with higher rate of early ileal lesions (i1) (41.6% vs 17.1%; aRR 3.49 (95% CI 1.01 to 12.04), p=0.048) or ileal lesions (i2b+i3) (38.2% vs 17.1%; aRR 3.45 (95% CI 1.06 to 11.30), p=0.040) compared with no lesion (i0). AIEC within the surgical specimen was predictive of higher risk of i2b-endoscopic postoperative recurrence (POR) (aOR 2.54 (95% CI 1.01 to 6.44), p=0.049) and severe endoscopic POR (aOR 3.36 (95% CI 1.25 to 9.06), p=0.017). While only 5.0% (6/119) of the patients were AIEC-positive at both M0 and M6, 43.7% (52/119), patients with history of positive test for AIEC (M0 or M6) had higher risk of ileal endoscopic POR (aOR 2.32 (95% CI 1.01 to 5.39), p=0.048)), i2b-endoscopic postoperative recurrence (aOR 2.41 (95% CI 1.01 to 5.74); p=0.048) and severe endoscopic postoperative (aOR=3.84 (95% CI 1.32 to 11.18), p=0.013). AIEC colonisation was associated with a specific microbiota signature including increased abundance of Ruminococcus gnavus.
Conclusion Based on the postoperative recurrence model, our data support the idea that AIEC are involved in the early steps of ileal CD.
Trial registration number NCT03458195.
- BACTERIAL INTERACTIONS
- BACTERIAL PATHOGENESIS
- CROHN'S DISEASE
- E. COLI
Data availability statement
Data are available on reasonable request.
Statistics from Altmetric.com
Data availability statement
Data are available on reasonable request.
Footnotes
Twitter @h_sokol, @Matfum
Collaborators REMIND Study Group Investigators: Saint-Louis, Paris: Pierre Cattan, Mircea Chirica, Nicolas Munoz-Bongrand, Hélène Corte, Jean-Marc Gornet, Clotilde Baudry, Nelson Lourenco, Mariane Maillet, My-Linh Tran-Minh, Andrée Nisard; Saint-Antoine, Paris: Laurent Beaugerie, Anne Bourrier, Isabelle Nion-Larmurier, Cecilia Landman, Julien Kirchgesner, Xavier Dray, Ulrika Chaput, Marine Camus, Philippe Marteau, Loic Brot, Najim Chafai, Jeremie H. Lefevre, Clotilde Debove, Yann Parc, Magali Svreck, Nadia Hoyau-Idrissi; Beaujon, Clichy: Nathalie Guedj, Yves Panis, Leon Maggiorri, Mariane Ferron, Yoram Bouhnik, Olivier Corcos; Clermont-Ferrand: Gilles Bommelaer, Marion Goutte, Anne Dubois, Caroline Chevarin, Marie Dodel, Dilek Coban; Lille: Pierre Desreumaux, Philippe Zerbib, Coralie Sommeville, Virginie Suffys; Amiens: Jean-Louis Dupas, Franck Brazier, Clara Yzet, Denis Chatelain, Christophe Attencourt, Charles Sabbagh, Martine Leconte; Lyon: Bernard Flourié, Yves François, Eddy Cotte, Anne-Laure Charlois, Peggy Falgon, Driffa Moussata, Marion Chauvenet, Sarah Boyer; Nice: Jérome Filippi, Paul Hofmann; REMIND: Carole Margalef, Patricia Detre.
Contributors Guarantor of the article: AB.
AB, HS, MA and NB designed the study, obtained funding and wrote the manuscript. AB, HS, BP and NB contributed to bioinformatics data analysis. All REMIND investigators contributed to the recruitment and follow-up of patients. MR and PS performed microbiological experiments and AIEC characterisation. All authors read and approved the final manuscript.
Funding This REMIND study has been supported by grants from MSD France, Association François Aupetit and the Helmsley Charitable Trust. This study was also supported by the Ministère de la Recherche et de la Technologie; Inserm (UMR 1071); INRAE (USC-2018), the French government’s IDEX-I-SITE initiative 16-IDEX-0001 (CAP 20-25) of the University of Clermont Auvergne; and the Inserm National Programme 'Microbiote'.
Disclaimer The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
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