Introduction

Treatment of irritable bowel syndrome (IBS) comprises a multidisciplinary approach that is tailored to an individual patient, including educative, psychotherapeutic, and dietary interventions. Due to several limiting factors, including limited resources, currently not all IBS patients receive adequate treatment.
Digital health applications (DiGAs) are predominantly app-based digital therapeutics controlled by the German Federal Institute for Drugs and Medical Devices (BfArM). By providing guided self-help, DiGAs are considered promising treatment options for chronic conditions such as IBS, thereby closing gaps in healthcare.

Aims & Methods

The aim of this study was to prove the superiority of a BfArM registered DiGA intended to treat IBS compared to waiting list.
378 adults with diagnosed IBS were randomized to either using the DiGA for 12 weeks (intervention group, n = 188), or to using a modified sham app that only contained the measuring instruments, i.e., questionnaires used for this study (control group, n = 190). Both groups had access to uncontrolled add on care ad libitum.
The DiGA provided an in-app symptom journal and a personalized treatment plan containing recommendations from the fields of nutrition therapy (low-FODMAP diet) and psychotherapy (psychoeducation, cognitive-behavioral therapy, or gut-directed hypnosis).
The primary outcomes were symptom severity reduction, measured using the Irritable Bowel Syndrome - Severity Scoring System (IBS-SSS), quality of life improvement, measured using the Irritable Bowel Syndrome - Quality of Life (IBS-QOL) questionnaire, work productivity impairment reduction & activity impairment reduction, measured using the Work Productivity and Activity Impairment: Irritable Bowel Syndrome (WPAI:IBS) questionnaire, and health literacy improvements, measured using the European Health Literacy Survey (HLS-EU-Q16).
Outcomes were assessed at baseline and at week 12 (postintervention). The primary analysis was based on the intention-to-treat principle and used linear mixed models. An improvement of at least 50 points on the IBS-SSS scale was considered clinically relevant.

Results

Patients randomized to use the DiGA experienced statistically significant greater improvement compared to patients randomized to the control group for symptom severity (p<.001; 95% CI -123.9, -79.9), quality of life (p<001; 95% CI 16.2, 22.1), work productivity impairment (p<.001; 95% CI -0.2, -0.1), activity impairment (p<.001; 95% CI -0.2, -0.1), and health literacy (p<.001; 95% CI 0.7, 1.8) after 12 weeks (postintervention).
66.5% of the intervention group patients (125/188) had a clinically relevant improvement of symptoms, evaluated by IBS-SSS, compared to 33.2% of the control group (63/190, odds ratio 4.871; p<.001; 95% CI 3.122, 7.601; number needed to treat=3).

Conclusion

The investigated DiGA was found to be largely effective in patients with IBS. It provides a treatment option that produces a significant, clinically relevant reduction of symptoms as well as significant improvements of quality of life, work productivity, and health literacy. Further studies should determine what long-term effects can be achieved, and how the use of the DiGA impacts health economic variables such as treatment costs for IBS.

Disclosure

Linda M. Weißer and André Sommer are employees of HiDoc Technologies GmbH.
Dongxing Zhao is a former employee of HiDoc Technologies GmbH.
Anja Mocek is an employee of IGES Institut GmbH.
Martin Storr has served as consultant for HiDoc Technologies GmbH.
The study was designed by IGES Institut GmbH and carried out by CSG Clinische Studien GmbH.
Funding was provided by HiDoc Technologies GmbH.

Introduction

The pathophysiological mechanism involved in irritable bowel syndrome (IBS) is thought to be multifactorial, involving the gut-brain axis and the immune system. Despite this complexity, dietary restriction of fermentable oligo-, dis-, mono- saccharides, and polyols (FODMAPs) has become the first line of treatment, improving symptoms in up to 80% of patients (1). FODMAPs are poorly absorbed in the small intestine and serve as a substrate for the colonic microbiota, which has been proposed as a key mediator of FODMAP tolerance and symptom development. Considering that both the gut microbiota and the (in)tolerance to individual FODMAPs are highly personalised (2), there is a growing need to understand the host-microbiota interactions underlying individual responses to FODMAP restriction and intake. This personalised interplay may be key to more targeted dietary interventions for IBS.

Aims & Methods

We aimed to disentangle the role of the gut microbiota in FODMAP tolerance by exploring microbial dynamics upon restriction and reintroducing individual FODMAPs. To this end, we performed 16S rRNA gene sequencing of over 1,700 faecal samples from 463 IBS patients participating in two clinical trials: a) The DOMINO trial (3), where primary-care patients underwent a FODMAP-lowering diet and b) A cohort of 117 tertiary-care patients underwent a strict FODMAP-restriction followed by a blinded re-introduction of 6 FODMAPs powders (2). Response to the diet was defined as a reduction of at least 50 points on the IBS symptom severity scale. Linear and logistic mixed models were used to assess the relation between the microbiome, response to dietary intervention, host genetics and 32 blood and faecal parameters.

Results

Participants with dysbiotic microbiota at baseline were shown to be less likely to respond to the dietary restriction (p-value=0.01). These participants also showed higher levels of fecal calprotectin, secretory IgA and eosinophil-derived neurotoxin, suggesting immune activation in this subgroup of IBS patients (p-value<0.05). In both cohorts, limiting FODMAP intake was associated with decreased Bifidobacterium abundance (FDR<0.01). Moreover, a dose-dependent effect was observed as depletion was less severe in the FODMAP-lowering DOMINO diet. This effect was independent of response and IBS subtype. Furthermore, total bacterial biomass did not change during the restriction or the reintroduction period. However, we found 25 significant associations between individual FODMAPs and gut bacteria. The reintroduction of galacto-oligosaccharides and fructans restored the levels of Bifidobacterium, while polyols increased the abundance of Anaerostipes, regardless of participants’ tolerance (FDR<0.05). In addition, we observed distinct dynamics in the gut microbiota associated with the tolerance of specific FODMAPs, although they did not reach significance after multiple testing corrections at the current sample size. For example, participants intolerant to sorbitol showed an increase in Alistipes upon exposure to this compound (p-value<0.05, FDR>0.05).

Conclusion

Our results suggest that microbiota composition at baseline influences the clinical response to FODMAP restriction. A low-FODMAP diet does not induce drastic changes in the microbiome composition, although we confirmed the negative impact of dietary restriction on the abundance of Bifidobacterium. However, the less restrictive DOMINO diet results in a milder depletion, suggesting that moderate FODMAP reduction may better preserve beneficial microbiota while still offering symptom relief. Finally, we found evidence for a link between microbial dynamics and FODMAP tolerance, although this needs to be confirmed in larger cohorts.

References

(1) Staudacher HM, Whelan K The low FODMAP diet: recent advances in understanding its mechanisms and efficacy in IBS Gut 2017;66:1517-1527.
(2) Van den Houte K, Colomier E, Routhiaux K, Mariën Z, Schol J, Van den Bergh J, Vanderstappen J, Pauwels N, Joos A, Arts J, Caenepeel P, De Clerck F, Matthys C, Meulemans A, Jones M, Vanuytsel T, Carbone F, Tack J. Efficacy and Findings of a Blinded Randomized Reintroduction Phase for the Low FODMAP Diet in Irritable Bowel Syndrome. Gastroenterology. 2024
(3) Carbone F, Van den Houte K, Besard L DOMINO Study Collaborators, et al Diet or medication in primary care patients with IBS: the DOMINO study - a randomised trial supported by the Belgian Health Care Knowledge Centre (KCE Trials Programme) and the Rome Foundation Research Institute Gut 2022;71:2226-2232.

Disclosure

JT has given Scientific advice to AlfaWassermann, Allergan, Christian Hansen, Danone, Grünenthal, Ironwood, Janssen, Kiowa Kirin, Menarini, Mylan, Neutec, Novartis, Noventure, Nutricia, Shionogi, Shire, Takeda, Theravance, Tramedico, Truvion, Tsumura, Zealand and Zeria pharmaceuticals, has received research support from Shire, Sofar and Tsumura, and has served on the Speaker bureau for Abbott, Allergan, AstraZeneca, Janssen, Kyowa Kirin, Menarini, Mylan, Novartis, Shire, Takeda, Truvion and Zeria. Funding was provided by a Methusalem grant from Leuven University to JT This study was supported by a research grant from the Belgian Health Care Knowledge Centre (KCE).

Introduction

Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are common disorders of gut-brain interaction (DGBI), and bloating and visible abdominal distension are common symptoms among individuals with IBS and/or FD. Bloating refers to a subjective sensation of tension or pressure in the abdomen, which may or may not be reported together with visible abdominal distension. The underlying pathophysiological mechanisms may differ, with bloating suggested to be more related to hypersensitivity and visible abdominal distension to altered motility. The prevalence of these two symptoms in IBS and FD, especially as distinct symptoms, is not well known.

Aims & Methods

The aim was to investigate the link between bloating and distension with IBS and FD. Therefore, we performed a population-based internet survey of adults in the US, UK, and Mexico, including Rome IV IBS and FD diagnostic questions, somatization (PHQ-12), and psychological distress (PHQ-4). Four groups were created: those meeting the Rome IV criteria for IBS only, FD only, both IBS+FD, and a reference group including individuals without IBS, FD and organic diagnoses that could result in IBS- or FD-like symptoms. Within each group, we identified individuals who reported ≥weekly bloating alone (B), ≥weekly visible abdominal distension alone (D), ≥weekly combined B+D, or neither of both. The relationship between B, D and B+D in those with IBS and/or FD vs. the reference group was investigated using logistic regression models.

Results

The analysis included 5,448 participants (49.7% female; mean age 46.5 years, range 18-99), with 131 meeting criteria for IBS only, 360 for FD only, 217 for IBS+FD and 4,740 for the reference group. A larger proportion of individuals with IBS only (64.9%), FD only (50.6%), and especially those with IBS+FD (88.5%) reported bloating and/or visible abdominal distension compared to the reference group (13.7%). In the IBS only group, 16.0% reported bloating alone, 8.4% visible abdominal distension alone, and 40.5% combined bloating and visible abdominal distension. In the FD only group this was 12.8% (B), 8.9% (D), and 28.9% (B+D), and in the IBS+FD group 18.9% (B), 8.3% (D), and 61.3% (B+D), respectively. Reporting bloating alone or combined bloating and visible abdominal distension was strongly linked to fulfilling criteria for IBS only, FD only, and concomitant IBS+FD vs. the reference group, with weaker links for visible abdominal distension in the absence of bloating (Table). After adjusting for age, sex, BMI, psychological distress and somatization, the links persisted. The strongest association was observed between combined bloating and visible abdominal distension (vs. neither) and concomitant IBS+FD (vs. the reference group); adjusted odds ratio 28.6 [95%CI 17.6-46.6].

Conclusion

Bloating and visible abdominal distension as distinct and overlapping symptoms are strongly linked to IBS, FD, and concomitant IBS+FD in the general population. Assessing bloating and visible abdominal distension as separate symptoms may be important to enable individualized treatment for individuals with IBS and FD.