Award: Presidential Poster Award
Allen Lee, MD1, Krishna Rao, MD, MS2, Emily Haller, RD1, Lauren Van Dam, RD1, Jason Baker, PhD1, Lydia Watts, BS1, Shanti Eswaran, MD2, William D. Chey, MD, FACG3, Chung Owyang, MD2, Vincent Young, MD, PhD1, William Hasler, MD1
1University of Michigan School of Medicine, Ann Arbor, MI; 2University of Michigan, Ann Arbor, MI; 3Michigan Medicine, University of Michigan, Ann Arbor, MI
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, Fig. 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 (Fig. 1B). Responders to rifaximin (Fig. 2A) and low FODMAP diet (Fig. 2B) showed changes in several taxa at baseline and longitudinally compared with non-responders.
Discussion: 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.
Citation: Allen Lee, MD; Krishna Rao, MD, MS; Emily Haller, RD; Lauren Van Dam, RD; Jason Baker, PhD; Lydia Watts, BS; Shanti Eswaran, MD; William D. Chey, MD, FACG; Chung Owyang, MD; Vincent Young, MD, PhD; William Hasler, MD. P1258 - BASELINE AND LONGITUDINAL MICROBIAL CHANGES PREDICT RESPONSE TO RIFAXIMIN AND/OR DIET LOW IN FERMENTABLE OLIGOSACCHARIDES, DISACCHARIDES, MONOSACCHARIDES, AND POLYOLS IN IRRITABLE BOWEL SYNDROME. Program No. P1258. ACG 2019 Annual Scientific Meeting Abstracts. San Antonio, Texas: American College of Gastroenterology.