496 Baseline and Longitudinal Microbial Changes Predict Response to Rifaximin and/or Diet Low in Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols in Irritable Bowel Syndrome

Abstract

INTRODUCTION: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a chronic, disabling condition. Treatments for IBS-D, including rifaximin, a nonabsorbable antibiotic, and a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP), improve symptoms in ≤50% of patients. We hypothesized that changes in the gut microbiota predict response to treatment for IBS-D. METHODS: We randomized 17 patients meeting Rome IV criteria for IBS-D to receive either rifaximin 550 mg three times daily x 14 days or a low FODMAP diet x 4 wks. The primary outcome was proportion of responders to intervention defined by ≥30% improvement in mean daily abdominal pain or bloating scores. The secondary outcome was ≥50-point decrease in IBS-Severity Symptom Scoring (IBS-SSS) compared with baseline. Fecal samples were collected at baseline and 2, 4 and 5 wks. The microbial community in these specimens was characterized by 16S rRNA encoding-gene sequence analysis. RESULTS: There were 6 subjects (60.0%) in the rifaximin group and 4 subjects (57.1%) in the low FODMAP group that met the primary endpoint (P > .99) (Table 1). Patients in the rifaximin group had significant improvements in abdominal pain (P = .01), bloating (P = .02), and IBS-SSS (P = .009) compared with baseline. Patients in the low FODMAP group showed improvement in IBS-SSS only (P = .06) at the end of treatment. Responders to treatment had unique inter- and intra-individual temporal characteristics compared with non-responders. Responders to rifaximin and low FODMAP diet showed a distinct microbial community structure at baseline compared with non-responders (P = .001 for both, Figure 1A). Responders to rifaximin (P = .08) and low FODMAP diet (P = .01) also exhibited lower degrees of microbial community change during therapy compared with non-responders (Figure 1B). Responders to rifaximin (Figure 2A) and low FODMAP diet (Figure 2B) showed changes in several taxa at baseline and longitudinally compared with non-responders. CONCLUSION: Responders to therapy with rifaximin and low FODMAP diet show a distinct fecal microbial community structure at baseline. Many microbiome features at baseline predict response to treatment. Longitudinal analyses show responders have a more resilient community structure to either rifaximin or dietary modification compared with non-responders. The functional significance of these microbial changes in responders vs. non-responders is unclear, but may be the focus of future studies.