Methods: Patients with IBS-D (Rome III criteria) were entered into the open-label (OL) phase in which they were treated with RFX 550 mg TID for 2 weeks, followed by a 4-week follow-up period. Responders based on a composite endpoint of abdominal pain and stool consistency improvements during ≥2 of 4 weeks were followed until they relapsed (up to 18 additional weeks), at which time they were randomized to receive 2 double-blind (DB) repeat treatments (RFX 550 mg TID or placebo [PBO] for 2 weeks), separated by 10 weeks. All patients provided stool samples at the beginning and end of OL treatment, beginning and end of the first repeat treatment, and end of study. Patients were randomly selected for inclusion in the stool microbiota sequencing substudy in a manner that incorporated responders and nonresponders. Genomic characterization of microbiota was accomplished using 16S rRNA bacterial deep gene sequencing. Metrics to describe the data included the diversity index, composed of measures of richness (number of families in each sample corrected for different samples having different number of sequences), evenness (as calculated by Shannon equitability, with values ranging from 0 to 1, and 1 being complete evenness), and Shannon diversity (a measure of overall community complexity).
Results: A total of 103 patients (mean age, 47.9 years; 74% female) were randomly selected for inclusion in the stool microbiota substudy, of which 73 (37 in RFX group and 36 in PBO group, evenly matched according to demographics) participated in the DB phase. At baseline of the DB phase, Shannon diversity was 1.786 and 1.733 in the RFX and PBO groups, respectively; after the 2-week treatment period, Shannon diversity was 1.698 and 1.743 (P = 0.4), respectively, and remained essentially unchanged in the follow-up period. No significant changes in the evenness of the microbiota were observed within or between the treatment groups in the DB phase. The richness of the microbiota in patients treated with DB PBO remained unchanged, whereas richness decreased at Week 2 in patients treated with RFX compared with DB baseline (P = 0.03) and compared with PBO (P = 0.02); this change associated with RFX treatment appeared to be short-lived as it was not detected in the follow-up period.
Conclusions: Overall, no sustained disturbance of the stool microbiota was observed in patients during repeat treatment with rifaximin compared with patients taking a single course of OL RFX followed by DB PBO.