A Longitudinal Study to Identify IBS Phenotypes Using Fecal Microbiota and Hydrogen Breath Testing

Diarrhea-predominant irritable bowel syndrome (IBS-D) is a highly prevalent but poorly
understood condition with limited treatment options. Recent evidence has established small
intestinal bacterial overgrowth (SIBO) and alterations in fecal microbiota as potential
etiologies in the pathogenesis of IBS-D. Current therapies, including a nonabsorbable
antibiotic rifaximin or diet low in fermentable oligosaccharides, disaccharides,
monosaccharides, and polyols (FODMAP), show efficacy in 50% or less of patients [1-4]. It has
been postulated that limited responses to therapies may stem from failure to identify
distinct subgroups in IBS-D stratified by gut microbial profiles. In this proposal, we will
randomize IBS-D patients to receive either rifaximin or low FODMAP dietary intervention. We
will then longitudinally follow the results of fecal microbiota-derived data as well as
hydrogen breath tests to define SIBO. We will use these methods to test the hypotheses that:
(i) distinct IBS-D phenotypes can be generated by defining fecal microbial populations as
well as delineating the presence or absence of SIBO; and (ii) longitudinal analyses using
microbe-derived metrics and SIBO status may relate to response to treatment with rifaximin or
low FODMAP dietary intervention.

Inclusion Criteria:

- Adult subjects > or = 18 years of age who meet Rome IV criteria for IBS-D

- Prior colonoscopy or sigmoidoscopy within the past 2 years with random colon biopsies
to exclude the presence of microscopic colitis

Exclusion Criteria:

- Underlying celiac disease, inflammatory bowel disease, or other organic disease that
could explain their symptoms.

- Subjects with a history of GI tract surgery, except for appendectomy, will also be
excluded from the study.

- Antibiotics taken within 3 months prior to enrollment will not be permitted.

- Subjects on probiotics must discontinue their use at least 1 month prior to
enrollment.

- Subjects who have previously received formal dietary education for IBS, including a
low FODMAP diet, or previously received antibiotics, including rifaximin, for
treatment of IBS-D will be excluded from the study.