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Alterations in the Intestinal Microbiome (Dysbiosis) as a Predictor of Relapse After Infliximab Withdrawal in Crohn's Disease

Rajca, Sylvie MD1; Grondin, Virginie BS1; Louis, Edouard MD, PhD2; Vernier-Massouille, Gwenola MD3; Grimaud, Jean-Charle MD, PhD4; Bouhnik, Yoram MD, PhD5; Laharie, David MD, PhD6; Dupas, Jean-Louis MD, PhD7; Pillant, Helene MD8; Picon, Laurence MD9; Veyrac, Michel MD10; Flamant, Mathurin MD, PhD11; Savoye, Guillaume PhD12; Jian, Raymond MD, PhD13; Devos, Martine MD, PhD14; Paintaud, Gilles MD, PhD15; Piver, Eric MD, PhD9; Allez, Matthieu MD, PhD16; Mary, Jean Yves PhD17; Sokol, Harry MD, PhD1; Colombel, Jean-Frederic MD, PhD18; Seksik, Philippe MD, PhD1

doi: 10.1097/MIB.0000000000000036
Original Basic Science Articles

Background: Crohn's disease (CD)–associated dysbiosis could predispose patients to relapse. Gut microbiota composition of patients from the prospective cohort study designed to identify predictive factors of clinical relapse after infliximab discontinuation (STORI Study) was investigated to determine the impact of dysbiosis in CD relapse.

Methods: Fecal samples from 33 patients with CD in this cohort were collected at baseline, 2 months, 6 months, and at the end of the follow-up period (19 relapsers and 14 nonrelapsers). Healthy volunteers subjects (n = 29) were used as a control group. The fecal microbiota composition was assessed using quantitative PCR, and comparisons between the patient groups were made at different time points using the Wilcoxon test. The analysis of the time-to-relapse was performed according to the baseline median level of each bacterial signal.

Results: Dysbiosis was observed in patients with CD compared with healthy subjects, and it was characterized by low mean counts of Firmicutes (Clostridium coccoides [P = 0.0003], C. leptum [P < 0.0001], and Faecalibacterium prausnitzii [P = 0.003]). Lower rates of Firmicutes were seen in relapsers compared with nonrelapsers. Moreover, a low rate of F. prausnitzii (P = 0.014) and a low rate of Bacteroides (P = 0.030) predicted relapse independently from high C reactive protein level (P = 0.0001).

Conclusions: In this work, we report that CD-associated dysbiosis, characterized by a decrease in Firmicutes, correlates with the time-to-relapse after infliximab withdrawal. A deficit in some bacterial groups or species, such as F. prausnitzii, may represent a predictive factor for relapse. Restoring normobiosis in CD could be a new goal for optimal CD management.

Article first published online 30 April 2014.

1Sorbonne Universités - UPMC Univ Paris 06, INSERM ERL 1157, CNRS UMR 7203 LBM and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), CHU Saint-Antoine, Paris, France;

2Centre Hospitalier Universitaire de Liège, Liège, Belgium;

3Université Lille Nord de France and CHRU Lille, Lille, France;

4Hôpital Nord, Centre d'investigation clinique Marseille Nord, Université Méditerranée, Marseille, France;

5INSERM U853, Hôpital Beaujon, Université Paris Diderot, Paris, Clichy, France;

6Université Bordeaux, Bordeaux, France;

7Hôpital Nord, Amiens, France;

8Hôpital Henri Mondor, Créteil, France;

9Hôpital Trousseau, Tours, France;

10Hôpital Saint-Eloi, Montpellier, France;

11Hôtel Dieu, Nantes, France;

12Hôpital Charles Nicolle, Université de Rouen, Rouen, France;

13Hôpital Européen Georges Pompidou, Paris, France;

14University of Ghent, Ghent, Belgium;

15Université François Rabelais de Tours, Tours, France;

16Hôpital Saint-Louis, Université Paris Diderot, Paris, France;

17INSERM U717, Biostatistics and clinical epidemiology, Université Paris Diderot, Paris, France; and

18Icahn Medical School of Medicine at Mount Sinai, New York, New York.

Reprints: Philippe Seksik, MD, PhD, Service de Gastroentérologie et Nutrition, Hôpital St-Antoine, 184 rue du Faubourg St-Antoine, Paris 75571, France (e-mail: philippe.seksik@sat.aphp.fr).

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.ibdjournal.org).

This work has been granted by the Association Francois Aupetit (#21102009).

The authors have no conflicts of interest to disclose.

Received December 31, 2013

Accepted February 25, 2014

© Crohn's & Colitis Foundation of America, Inc.
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