Sylvie Rajca1, Virginie Grondin, Edouard Louis, Gwenola Vernier-Massouille, Jean-Charle Grimaud, Yoram Bouhnik, David Laharie, Jean-Louis Dupas, Helene Pillant, Laurence Picon, Michel Veyrac, Mathurin Flamant, Guillaume Savoye, Raymond Jian, Martine Devos, Gilles Paintaud, Eric Piver, Matthieu Allez, Jean Yves Mary, Harry Sokol, Jean-Frederic Colombel, Philippe Seksik. 1. 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.
Abstract
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.
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.
Authors: E Quévrain; M A Maubert; C Michon; H Sokol; P Seksik; F Chain; R Marquant; J Tailhades; S Miquel; L Carlier; L G Bermúdez-Humarán; B Pigneur; O Lequin; P Kharrat; G Thomas; D Rainteau; C Aubry; N Breyner; C Afonso; S Lavielle; J-P Grill; G Chassaing; J M Chatel; G Trugnan; R Xavier; P Langella Journal: Gut Date: 2015-06-04 Impact factor: 23.059
Authors: James D Lewis; Eric Z Chen; Robert N Baldassano; Anthony R Otley; Anne M Griffiths; Dale Lee; Kyle Bittinger; Aubrey Bailey; Elliot S Friedman; Christian Hoffmann; Lindsey Albenberg; Rohini Sinha; Charlene Compher; Erin Gilroy; Lisa Nessel; Amy Grant; Christel Chehoud; Hongzhe Li; Gary D Wu; Frederic D Bushman Journal: Cell Host Microbe Date: 2015-10-14 Impact factor: 21.023
Authors: Giuseppina Liguori; Bruno Lamas; Mathias L Richard; Giovanni Brandi; Gregory da Costa; Thomas W Hoffmann; Massimo Pierluigi Di Simone; Carlo Calabrese; Gilberto Poggioli; Philippe Langella; Massimo Campieri; Harry Sokol Journal: J Crohns Colitis Date: 2015-11-15 Impact factor: 9.071