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

We thank Drs Bertin and Savarino for their interest in our paper and for their thoughtful and constructive comments 1. They have elegantly summarised the key messages of our study, particularly the importance of offering individualised treatment options for patients with irritable bowel syndrome (IBS) based on patient preferences, clinical context, and available healthcare resources. As demonstrated in our study, rifaximin and low FODMAP diet (LFD) therapy showed comparable overall efficacy in improving IBS symptoms 2. This supports a pragmatic, patient-centred approach in which treatment selection can be tailored according to individual needs and circumstances. Patients who are motivated, engaged, and keen on self-empowerment through dietary modification may reasonably opt for LFD therapy, particularly when access to trained dietitians is available. In contrast, in healthcare settings where dietitian resources are limited, or among patients who prefer a rapid onset of treatment efficacy and a less burdensome intervention, rifaximin may represent a more suitable and practical option. This flexibility in therapeutic choice is particularly relevant in real-world clinical practice, where time constraints, healthcare infrastructure, and patient expectations often influence management decisions 3. Bloating remains one of the most common and distressing symptoms experienced by patients with IBS and other disorders of gut–brain interaction 4. Despite its high prevalence and impact on quality of life, FDA-approved pharmacological options specifically targeting bloating remain limited. In our study, both treatment arms demonstrated beneficial effects on bloating 2. Notably, rifaximin was associated with significantly greater improvement in bloating compared with LFD among patients with the IBS-D subtype. This finding is clinically relevant and raises the intriguing possibility that rifaximin may have a broader role in the management of bloating beyond IBS-D, including conditions such as functional bloating or other DGBI 5. Further dedicated studies are warranted to explore this hypothesis. With regard to breath testing methodology, we employed 75 g of glucose, rather than 50 g, to enhance test sensitivity while maintaining specificity, and we included patients with methane overgrowth, in accordance with recommendations from recent Asian and American consensus statements 6, 7. Sulfide measurements were not performed as part of the breath test protocol. Nevertheless, we fully acknowledge the ongoing limitations and diagnostic challenges associated with hydrogen breath testing for small intestinal bacterial overgrowth (SIBO), including issues related to test standardisation, interpretation, and clinical relevance. IBS diagnosed using Rome IV criteria has been reported to represent a more severe disease phenotype. Although patients meeting Rome III criteria may exhibit less severe abdominal pain, studies have shown that their impairment in quality of life is often comparable 8, 9. Restricting diagnosis and treatment eligibility solely to Rome IV criteria may therefore inadvertently exclude a substantial number of patients who could otherwise benefit from effective therapies. Despite advances in clinical trials and evolving therapeutic strategies, treatment options for patients with severe or refractory IBS remain limited. An important future direction would be to evaluate the efficacy of combination therapy using LFD and rifaximin, and to determine whether this approach offers additive or synergistic benefits. Such studies would help address the clinically relevant question of whether two complementary therapies may be more effective than one, particularly in patients with persistent or complex symptom profiles. Kee Huat Chuah: conceptualization, writing – original draft. Qing Yuan Loo: writing – review and editing. Audrey Joe Chii Loh: writing – review and editing. Jing Yi Leong: writing – review and editing. Wah Loong Chan: writing – review and editing. Xin Hui Khoo: writing – review and editing. Kim Leng Wong: writing – review and editing. Sarala Panirsheeluam: writing – review and editing. Vicraman Natarajan: writing – review and editing. Ai Kah Ng: writing – review and editing. Hazreen Abdul Majid: writing – review and editing, supervision. Sanjiv Mahadeva: supervision, writing – review and editing. The authors have nothing to report. The authors' declarations of personal and financial interests are unchanged from those in the original article 2. 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.70533. The authors have nothing to report.