Introduction
Small intestinal bacterial overgrowth (SIBO) is a clinical syndrome with abdominal complaints and malabsorption. Despite concerns over cure rates, recurrence, and antibiotic resistance, rifaximin (RIF) remains the primary treatment. Berberine (BBR), an affordable traditional medicine, has demonstrated gut microbiota modulation, making it a promising alternative.
Aims & Methods
We conducted an open-label, non-inferiority randomized controlled trial (BRIEFSIBO) comparing BBR and RIF in SIBO patients. Patients were randomly assigned to receive either RIF or BBR. The primary outcome was breath test (BT) conversion to negative, with symptom scores and the Bristol stool scale as secondary outcomes.
Results
A total of 186 patients completed the study. No significant baseline differences were found between groups in age, gender, BMI, smoking, or alcohol use. BBR demonstrated non-inferior efficacy to RIF for primary outcome (BT eradication) at Week 2 (ITT: BBR 45%, RIF 51%, Z=2.407, P=0.008; PP: BBR 44%, RIF 47%, Z=2.4787, P=0.007) and Week 6 (ITT: BBR 53%, RIF 44%, Z=4.3244, P<0.001; PP: BBR 54%, RIF 45%, Z=4.077, P<0.001). What's more, BBR demonstrated non-inferior efficacy to RIF for secondary outcome (clinical improvement) at Week 2 (ITT: BBR 68%, RIF 75%, Z=2.9209, P=0.0017; PP: BBR 73%, RIF 72%, Z=3.3531, P=0.0004) and Week 6 (ITT: BBR 75%, RIF 80%, Z=2.8514, P=0.0022; PP: BBR 81%, RIF 86%, Z=3.0747, P=0.0011). Following a four-week period of discontinuation, the rate of combined expiratory and symptomatic relapse in patients treated with RIF was 8.57%. In contrast, no such relapses were observed in patients treated with BBR. BT values at 60–90 minutes and AUC decreased in both groups, though RIF showed recurrent peak values during follow-up. A novel breath peak acceleration parameter, reflecting local gut gas load, decreased in both groups. BBR significantly improved bloating at Week 6, whereas RIF improved bowel movement frequency. At Week 6, patients were classified into response, relapse, and nonresponse groups to identify optimal candidates for each drug. RIF responders showed significant improvement in bloating and bowel-related symptoms (P<0.05). Baseline gut microbiota analysis revealed significant β diversity differences between three groups in BBR but not in RIF. Genus-level microbiota composition differed between responders, with BBR responders exhibiting higher baseline proportions of Phascolarctobacterium, Klebsiella, and Haemophilus, and lower Coprobacter. At Week 6, both groups showed enriched Bacteroides, while BBR responders had elevated Phascolarctobacterium, Streptococcus, and Haemophilus, with lower Bifidobacterium.
Conclusion
BBR is non-inferior to RIF for SIBO treatment and offer a promising and cost-effectiveness new option.
References
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