Consolidation Therapy of Probiotics With Rifaximin Prevent Relapse in Rifaximin‐Responsive Diarrhea‐Predominant Irritable Bowel Syndrome: A Multicenter Randomized Clinical Trial

BACKGROUND AND AIM: Although rifaximin treatment achieves high remission rates in diarrhea-predominant irritable bowel syndrome (IBS-D), current therapeutic approaches remain ineffective in preventing disease recurrence. This study aimed to evaluate the relapse rates with Rifaximin after consolidation course with live Bacillus subtilis and Enterococcus faecium capsules (Medilac-S) and explore gut microbiota changes in these IBS-D patients. METHODS: We performed a multicenter, open-label, randomized trial. Participants responded to 2-week rifaximin were randomly assigned to receive Medilac-S for 4-week consolidation therapy or to no further treatment in a 2:1 ratio. The primary outcome is relapse rate. Secondary outcomes include IBS-Symptom Severity Score, IBS-quality of life, stool frequency and consistency, microbiota profiles, and adverse event incidence. RESULTS: 143 participants were randomized to Medilac-S or control group. The relapse rate was significantly lower in Medilac-S consolidation therapy group compared with patients receiving rifaximin only (40.00% [38/95] vs. 58.33% [28/48], p = 0.0378) at the end of follow-up. Furthermore, we observed a higher Firmicutes to Bacteroidota ratio and an increased abundance of Faecalibacterium and Streptococcus in patients who experienced relapse. The Medilac-S group achieved a significant reduction in bowel movement frequency (1.73 ± 0.75 vs. 2.53 ± 1.20, p < 0.001) and improvement of stool consistency (BSFS 4.38 ± 1.06 vs. 5.15 ± 0.95, p < 0.001). CONCLUSIONS: Our findings demonstrate that consolidation therapy with Medilac-S following clinical complete response to Rifaximin achieves sustained long-term remission in IBS-D, particularly in improvement of stool frequency/consistency and effective relapse prevention. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04074421.