A Randomized Trial of Rifaximin vs Low Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols Diet for Symptom Outcomes and Microbiome Changes in Irritable Bowel Syndrome.

BACKGROUND & AIMS: The low Fermentable Oligosaccharides, Disaccharides, Monosaccharides, And Polyols (FODMAP) diet (LFD) and rifaximin are effective in <50% individuals with irritable bowel syndrome (IBS), highlighting the need to identify predictors of treatment response. We therefore conducted a randomized controlled trial comparing LFD and rifaximin to identify microbial predictors of response.

METHODS

Sixty-five adults with diarrhea-predominant IBS (IBS-D) were randomized to LFD or rifaximin for 5 weeks. Primary endpoints were changes in mean daily abdominal pain and bloating at week 5 vs baseline. Secondary endpoints included changes in IBS Symptom Severity Score and Bristol Stool Form Scale at week 5 vs baseline. Exploratory endpoints included responders defined as ≥30% reduction in abdominal pain or bloating. Stool samples collected at weeks 0, 2, 4, and 5 underwent 16S rRNA sequencing, and glucose breath testing (BT) was performed at weeks 0 and 5.

RESULTS

Both LFD and rifaximin significantly improved abdominal pain (-0.29 with LFD vs -0.24 points/week with rifaximin); bloating (-0.29 vs -0.19 per week); and IBS Symptom Severity Score (-14.2 vs -13.3 per week) at week 5 (all P < .0001), with no significant change in Bristol Stool Form Scale. BT results were inconsistent predictors of response, with positive baseline hydrogen BT associated with lower odds of rifaximin response, and methane conversion at week 5 showed discordant associations with rifaximin response. In contrast, distinct baseline taxa were associated with treatment response. LFD responders had lower abundance of putative saccharolytic taxa (Butyricimonas, Bacteroides, Intestinibacter), whereas rifaximin responders were enriched in taxa with putative short-chain fatty acid-producing and bile acid-modifying potential (Ruminococcus, Coprococcus, Odoribacter). Nonresponders exhibited enrichment of putative proteolytic taxa (Bilophila, Alistipes, Prevotella).

CONCLUSIONS

LFD and rifaximin are equally effective for IBS-D, with distinct microbial predictors of response. However, these findings require validation before informing personalized treatment approaches.

CLINICALTRIALS: gov, Number: NCT03219528.