Letter: Rifaximin Versus Low FODMAP Diet in IBS : What the Primary Endpoint Does Not Tell Us

We read with great interest the study by Chuah et al. 1 the first randomised controlled trial directly comparing rifaximin and the low FODMAP diet (LFD) in irritable bowel syndrome (IBS). Both treatments are recommended as treatment options by current guidelines 2, 3, yet head-to-head data have been lacking until now. The authors report comparable efficacy at week 4, with 56% and 48% composite symptom response rates for rifaximin and LFD, respectively. Moreover, both treatments were well tolerated, with no serious adverse events and similar rates of minor adverse events. However, beyond efficacy and safety equivalence, two findings deserve particular attention. First, rifaximin achieved significantly faster symptom relief at week 2 for global symptoms (90% vs. 72%), bloating (84% vs. 58%), and abdominal pain (80% vs. 58%). Second, treatment adherence differed markedly: 95.9% with rifaximin versus 77.8% with LFD (p = 0.008). The bloating findings are particularly noteworthy as functional bloating is highly prevalent in IBS (62%–76% of patients). Recent UEG/ESNM guidelines on functional bloating endorse rifaximin as a treatment option, citing meta-analytic evidence of efficacy (OR 1.55; 95% CI: 1.23–1.96) 4. The persistent superiority of rifaximin for bloating in IBS-D at week 4 (85.7% vs. 57.6%, p = 0.010) aligns with these recommendations and may have substantial clinical relevance. The adherence gap highlights a well-recognised challenge with dietary interventions. Even with dietitian guidance, compliance with the LFD declines progressively, particularly in settings with limited specialist support 5. The recent network meta-analysis by Cuffe et al. confirmed the LFD's efficacy but noted that adherence was formally assessed in only 11 of 28 eligible trials 6. The SIBO subgroup analysis warrants careful interpretation. While rifaximin's efficacy for SIBO eradication is well-established, with a meta-analysis reporting an overall eradication rate of 70.8% 7, the diagnostic approach in this trial has limitations. The glucose hydrogen breath test, although having reasonable specificity (80%–85%), may miss distal small bowel bacterial overgrowth since glucose is absorbed proximally 8. Furthermore, the 75 g dose used in this trial may have increase false-positive rates as compared to the standard 50 mg dose. Additionally, measuring only hydrogen may have missed patients with methane- or sulfide-dominant overgrowth. The use of Rome III rather than Rome IV criteria, while potentially more sensitive in Asian populations where abdominal pain tends to be less frequent, limits comparability with recent trials. The 4-week follow-up precludes assessment of durability, although rifaximin's effects persist for up to 4 months with retreatment remaining effective 9. Perhaps the most valuable contribution of this study lies in demonstrating that treatment selection in IBS extends beyond efficacy comparisons. When both options show similar effectiveness and safety, factors such as speed of onset, adherence feasibility, and resource availability become decisive. In resource-limited settings, rifaximin offers a practical alternative; for patients preferring non-pharmacological approaches, the LFD remains valuable. Future studies should evaluate sequential or combined approaches, as synergistic effects between rifaximin and dietary interventions have been demonstrated 10, with longer follow-up to assess durability. Luisa Bertin: conceptualization, investigation, writing – review and editing, writing – original draft, data curation. Edoardo Vincenzo Savarino: conceptualization, investigation, writing – review and editing, project administration, supervision. The authors have nothing to report. Edoardo Vincenzo Savarino has served as speaker for Abbvie, Agave, AGPharma, Alfasigma, Aurora Pharma, CaDiGroup, Celltrion, Dr. Falk, EG Stada Group, Fenix Pharma, Fresenius Kabi, Galapagos, Janssen, JB Pharmaceuticals, Innovamedica/Adacyte, Malesci, MayolyBiohealth, Omega Pharma, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda, Tillots, Unifarco; has served as consultant for Abbvie, Agave, Alfasigma, Biogen, Bristol-Myers Squibb, Celltrion, DiademaFarmaceutici, Dr. Falk, Fenix Pharma, Fresenius Kabi, Janssen, JB Pharmaceuticals, Merck he received research support from Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco, Zeta Farmaceutici. Luisa Bertin has served as speaker for Edra SPA, Takeda. This article is linked to Chuah et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70420 and https://doi.org/10.1111/apt.70553. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.