Alterations in the intestinal microbiome (dysbiosis) as a predictor of relapse after infliximab withdrawal in Crohn's disease.

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.