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Original research
Prominence of ileal mucosa-associated microbiota to predict postoperative endoscopic recurrence in Crohn’s disease
  1. Harry Sokol1,2,3,
  2. Loic Brot1,
  3. Carmen Stefanescu4,
  4. Claire Auzolle5,6,
  5. Nicolas Barnich7,
  6. Anthony Buisson7,8,
  7. Mathurin Fumery9,
  8. Benjamin Pariente10,
  9. Lionel Le Bourhis5,
  10. Xavier Treton4,
  11. Stéphane Nancey11,
  12. Matthieu Allez5,6,
  13. Philippe Seksik1,2
  14. REMIND Study Group Investigators
    1. 1 Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Hôpital Saint Antoine, Service de Gastroenterologie, Paris, France
    2. 2 Department of Gastroenterology, Saint-Antoine Hospital, Assitance Publique-Hôpitaux de Paris (AP-HP), Paris, France
    3. 3 INRA, UMR1319 Micalis, AgroParisTech, Jouy-en-Josas, France
    4. 4 Department of Gastroenterology, Beaujon Hospital, Assitance Publique-Hôpitaux de Paris (AP-HP), Clichy, France
    5. 5 INSERM UMRS 1160, Paris Diderot, Sorbonne Paris-Cité University, Paris, France
    6. 6 Gastroenterology Department, Hôpital Saint-Louis hospital, Assitance Publique-Hôpitaux de Paris (AP-HP), Paris, France
    7. 7 Université Clermont Auvergne/Inserm U1071; USC-INRA 2018, Microbes, Intestin, Inflammation et Susceptibilité de l’Hôte (M2iSH), Clermont-Ferrand, France
    8. 8 Service de Médecine de l’Appareil Digestif, Centre Hospitalier Clermont-Ferrand, France
    9. 9 Hepatogastroenterology Department, Amiens University Hospital, Amiens, France
    10. 10 Gastroenterology Department, Claude Huriez Hospital, University of Lille 2, Lille, France
    11. 11 Gastroenterology Department, Centre Hospitalier Lyon-Sud, Lyon, France
    1. Correspondence to Dr Harry Sokol, Service de Gastro-entérologie, Hôpital Saint-Antoine, 75012 Paris, France; harry.sokol{at}


    Objective Following ileal resection for Crohn’s disease (CD), recurrence is very frequent. Although several clinical risk factors of recurrence have been identified, predicting relapse remains challenging. Performing an ileocolonoscopy within the first year after surgery is currently recommended to assess endoscopic recurrence and to adjust the treatment. We took advantage of a large prospective multicentric cohort to investigate the role of the ileal mucosa-associated microbiota in postoperative endoscopic recurrence.

    Patients and methods Ileal mucosa-associated microbiota was analysed by 16S sequencing at the time of surgery and/or of endoscopic evaluation in 201 patients (288 samples in total) prospectively recruited in France.

    Results Ileal mucosa-associated microbiota exhibits profound changes following surgery in CD. Compared with non-recurrence setting, endoscopic recurrence is associated with strong changes in ileal mucosa-associated microbiota that are highly reminiscent of those observed generally in ileal CD compared with healthy subjects with a reduction in alpha diversity, an increase in several members of the Proteobacteria phylum and a decrease in several members of the Lachnospiraceae and the Ruminococcaceae families within the Firmicutes phylum. At the time of surgery, we identified several bacterial taxa associated with endoscopic recurrence and that can better predict relapse than usual clinical risk factors.

    Conclusion Surgery has an important impact on ileal mucosa-associated microbiota. Postoperative endoscopic recurrence is associated with changes in microbiota composition and alpha diversity. The gut microbiota has the potential to predict postoperative evolution and recurrence.

    • colonic microflora
    • Crohn’s disease

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    • Contributors HS: study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript and statistical analysis; LB: acquisition of data and technical support; PS and MA: study concept and design, acquisition of data and critical revision of the manuscript; CS, CA, AB, MF, MA, XT and SN: acquisition of data and technical support; NB: acquisition of data and critical revision of the manuscript. All the authors revised and approved the manuscript.

    • Funding This study has been supported by grants from MSD France, Association François Aupetit, the Helmsley Charitable Trust and Inserm.

    • Competing interests MA received honoraria from Abbvie, MSD, Janssen, Takeda, Pfizer, Novartis, Ferring, Tillots, Celgene and Genentech/Roche. CA, NB, LLB and CS declares no competing interest. SN received honoraria from MSD, Abbvie, Takeda, Janssen, HAC Pharma, Tillots, Ferring and Novartis. AB received honoraria from MSD, Abbvie, Ferring, Takeda, Vifor Pharma, Sanofi‐Aventis, Hospira and Janssen. BP received honoraria from AbbVie, MSD, Takeda, Janssen, Bioagaran and Ferring. MF received honoraria from AbbVie, MSD, Takeda, Janssen, Pfizer, Ferring and Boehringer. HS received unrestricted study grants from Danone, Biocodex and Enterome; was a board member and a consultant, or received lecture fees from Carenity, Abbvie, Astellas, Danone, Ferring, Mayoly Spindler, MSD, Novartis, Roche, Tillots, Enterome, Maat, BiomX, Biose, Novartis and Takeda; and was cofunder of Nextbiotix. XT received honoraria from Abbvie, MSD, Takeda, Ferring, Norgine and Janssen. PS received honoraria from Takeda, MSD, Biocodex, Ferring and Abbvie, and non-financial support from Takeda.

    • Ethics approval The ethical committee of Hospital Saint-Louis approved this study (CPP#2009/17).

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • 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, Sylvie Rajca, Elodie Quevrain, Loic Brot, Najim Chafai, Jeremie Lefevre, Emmanuel Tiret, Magali Svreck, Nadia Hoyau-Idrissi, Jean François Flejou; Beaujon, Clichy: Nathalie Guedj, Yves Panis, Leon Magiorri, Mariane Feron, Yoram Bouhnik, Olivier Corcos; Lariboisière, Paris: Xavier Dray, Ulrika Chaput, Philippe Marteau; Clermont-Ferrand: Gilles Bommelaer, Marion Goutte, Emilie Vazeille, Michael Rodrigues, Pierre Sauvanet, Dilek Coban; Lille: Pierre Desreumaux, Maria Nachury, Coralie Sommeville; Amiens: Jean-Louis Dupas, Franck Brazier, Denis Chatelain, Christophe Attencourt, Charles Sabbagh, Martine Leconte; Lyon: Gilles Boschetti, Bernard Flourié, Yves François, Eddy Cotte, Anne-Laure Charlois, Peggy Falgon, Driffa Moussata, Marion Chauvenet, Sarah Boyer, Hélène Hafjisavvas; Nice: Xavier Hebuterne, Jérome Filippi, Paul Hofmann, Jessica Lechardeur; REMIND: Madeleine Bezault, Carole Margalef, Patricia Detre.

    • Patient consent for publication Not required.