Long-Term Effects of a Web-Based Low-FODMAP Diet Versus Probiotic Treatment for Irritable Bowel Syndrome, Including Shotgun Analyses of Microbiota: Randomized, Double-Crossover Clinical Trial.

Dorit Vedel Ankersen,Suzanne Frahm,Lisbeth Jensen,Mette Bennedsen,Moritz Emanuel Beber,Petra Weimers,Johan Burisch,Nicolai Vad,Pia Munkholm,Kristine Paridaens,Dorte Marker,Sanaz Saboori,Malte Rosager Hansen,Eva Lund Fjordside,Terje Rannem,Anne Birgitte Haaber,Christian Lieven

doi:10.2196/30291

Abstract

BackgroundThe long-term management of irritable bowel syndrome (IBS) poses many challenges. In short-term studies, eHealth interventions have been demonstrated to be safe and practical for at-home monitoring of the effects of probiotic treatments and a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs). IBS has been linked to alterations in the microbiota.ObjectiveThe aim of this study was to determine whether a web-based low-FODMAP diet (LFD) intervention and probiotic treatment were equally good at reducing IBS symptoms, and whether the response to treatments could be explained by patients’ microbiota.MethodsAdult IBS patients were enrolled in an open-label, randomized crossover trial (for nonresponders) with 1 year of follow-up using the web application IBS Constant Care (IBS CC). Patients were recruited from the outpatient clinic at the Department of Gastroenterology, North Zealand University Hospital, Denmark. Patients received either VSL#3 for 4 weeks (2 × 450 billion colony-forming units per day) or were placed on an LFD for 4 weeks. Patients responding to the LFD were reintroduced to foods high in FODMAPs, and probiotic responders received treatments whenever they experienced a flare-up of symptoms. Treatment response and symptom flare-ups were defined as a reduction or increase, respectively, of at least 50 points on the IBS Severity Scoring System (IBS-SSS). Web-based ward rounds were performed daily by the study investigator. Fecal microbiota were analyzed by shotgun metagenomic sequencing (at least 10 million 2 × 100 bp paired-end sequencing reads per sample).ResultsA total of 34 IBS patients without comorbidities and 6 healthy controls were enrolled in the study. Taken from participating subjects, 180 fecal samples were analyzed for their microbiota composition. Out of 21 IBS patients, 12 (57%) responded to the LFD and 8 (38%) completed the reintroduction of FODMAPs. Out of 21 patients, 13 (62%) responded to their first treatment of VSL#3 and 7 (33%) responded to multiple VSL#3 treatments. A median of 3 (IQR 2.25-3.75) probiotic treatments were needed for sustained symptom control. LFD responders were reintroduced to a median of 14.50 (IQR 7.25-21.75) high-FODMAP items. No significant difference in the median reduction of IBS-SSS for LFD versus probiotic responders was observed, where for LFD it was –126.50 (IQR –196.75 to –76.75) and for VSL#3 it was –130.00 (IQR –211.00 to –70.50; P>.99). Responses to either of the two treatments were not able to be predicted using patients’ microbiota.ConclusionsThe web-based LFD intervention and probiotic treatment were equally efficacious in managing IBS symptoms. The response to treatments could not be explained by the composition of the microbiota. The IBS CC web application was shown to be practical, safe, and useful for clinical decision making in the long-term management of IBS. Although this study was underpowered, findings from this study warrant further research in a larger sample of patients with IBS to confirm these long-term outcomes.Trial RegistrationClinicalTrials.gov NCT03586622; https://clinicaltrials.gov/ct2/show/NCT03586622

Highlights

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that affects 10% to 20% of the population in westernized countries [1]
The web-based low-FODMAP diet (LFD) intervention and probiotic treatment were efficacious in managing IBS symptoms
The IBS Constant Care (IBS CC) web application was shown to be practical, safe, and useful for clinical decision making in the long-term management of IBS

Summary

Introduction

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that affects 10% to 20% of the population in westernized countries [1]. The pathophysiology of IBS is not fully understood, but some of the underlying mechanisms include altered gastrointestinal motility, visceral hypersensitivity, psychosocial disturbance, low-grade inflammation, altered gut-brain function, and microbial ecosystem dysbiosis [3,6]. Managing IBS continues to be challenging because of the complexity of its chronicity, heterogeneous patient groups with and without comorbidities, and a lack of both diagnostic tools and well-documented treatment strategies for long-term purposes. Treatment strategies for IBS range from lifestyle and dietary advice to pharmacological solutions that generally target only the primary symptom. The long-term management of irritable bowel syndrome (IBS) poses many challenges.

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