Introduction

​​​​​​​​​​​​​​​Irritable bowel syndrome (IBS) is a highly prevalent chronic gastrointestinal disorder.¹ Physical activity (PA) improves IBS symptoms² and may be recommended among first-line interventions.^3
​Digital Apps may increase PA,⁴ but whether this intervention can improve symptoms in patients with IBS has not yet been investigated.

Aims & Methods

The aim of this randomized controlled trial was to evaluate the effects of PA prescription with the use of a mobile App in comparison with PA prescription alone on IBS symptoms and PA levels in patients with IBS.
From June to October 2022, we enrolled 97 consecutive patients with IBS defined according to the Roma IV criteria. 22 patients aged <18 or >60 years or with comorbidities limiting PA were excluded.
Patients were randomized to two intervention groups: 1) (Not APP) PA prescription with 10 min counselling according to the recommendations for IBS of Exercise is Medicine⁵ or 2) (APP) the same PA prescription with the indication to use the mobile App Google Fit (Google, Mountain View, USA) after a brief explanation. This App is free and with no advertisements, available both for IOS and android, and available in different languages including Italian. It promotes PA according to the latest World Health Organization (WHO) guidelines and it has been already used and validated in other studies.^6,7 Other treatments for IBS were allowed in both groups. Patients were evaluated at the first visit (T0) and after 3 months (T3). The severity of IBS symptoms (primary endpoint) was assessed by the Irritable Bowel Severity Scoring System (IBS-SSS). The Structured Assessment of Gastrointestinal Symptoms Scale (SAGIS), the Hospital Anxiety and Depression Scale (HADS), and the Bristol Stool Scale (BSS) were also used. The adherence to WHO guidelines for aerobic physical activity, and PA levels, were measured as Metabolic Equivalent of the Task (MET) minutes per week through the International Physical Activity Questionnaire-Short Form (IPAQ-SF).
Statistical analysis was performed with R 4.2.3.

Results

Seventy-five patients with IBS (mean age 41, SD ± 11.7 years; 70 % female) were randomized. Baseline characteristics of the two groups (age, sex, IBS subtypes, other treatments, IBS-SSS, SAGIS, HADS and BSS scores and PA levels) were not significantly different (data not reported). Three patients dropped out of the trial in the Not APP group. The improvement in IBS-SSS and in SAGIS total score in the App group were significantly greater than in the Not APP group, whereas the difference of the improvement in HADS between groups remained at borderline significance level (Table 1). Normalization of stool form was observed in 21% of patients in the Not APP group and in 41% of patients in the APP group (P= 0.077). Although PA increased in both groups, the increase was greater in the APP than in the Not APP group (MET min global activity at IPAQ-SF=791±1026 vs 262 ± 807; P=0.025) as well as the adherence to the WHO indications (41% vs 15 %, P=0.048). The increase of PA was significantly correlated with the improvement of IBS-SSS (r=0.33, P=0.03).

Table 1. Improvement (T3-T0 scores) of the IBS-SSS, SAGIS and HADS in the two groups after three months

Conclusion

Prescription of a digital APP promoting PA improved symptoms compared to PA counselling alone, suggesting that such Apps may be useful tools in the treatment of IBS.

References

1. Sperber AD, et al. Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study. Gastroenterology. 2021;160(1):99-114.e3.
2. Johannesson E, et al. Physical activity improves symptoms in irritable bowel syndrome: a randomized controlled trial. Am J Gastroenterol. 2011;106(5):915-922.
3. Vasant DH, et al. British Society of Gastroenterology guidelines on the management of irritable bowel syndrome. Gut. 2021;70(7):1214-1240.
4. Romeo A, et al. Can Smartphone Apps Increase Physical Activity? Systematic Review and Meta-Analysis. J Med Internet Res. 2019;21(3):e12053.
5. Costantino A, et al. A practical guide to the proper prescription of physical activity in patients with irritable bowel syndrome. Dig Liver Dis. 2022;54(11):1600-1604.
6. Bull FC, et al. World Health Organization 2020 guidelines on physical activity and sedentary behaviour. Br J Sports Med. 2020;54(24):1451-1462.
7. Menaspà, P., 2015. Effortless activity tracking with Google Fit. Br J Sports Med 49, 1598–1598

Introduction

Cognitive Behavioral Therapy (CBT) is an evidence-based treatment for Irritable Bowel Syndrome (IBS), demonstrating long-term improvements in symptoms and quality of life (QOL). However, its implementation is hindered by the complexity of treatment protocols, high time and financial costs, and limited accessibility in Japan.

Aims & Methods

This study aimed to develop a smartphone-based CBT application and evaluate its effectiveness in alleviating IBS symptoms.
Adults aged 18 or older who met the Rome IV criteria for IBS and scored ≥110 on the Japanese version of the IBS Symptom Severity Index (IBSSI-J) were enrolled. Twenty-six participants were randomly assigned to either the intervention group (n = 14) or the waiting-list control group (n = 12). Outcome measures included the IBSSI-J, Japanese versions of the IBS-QOL (IBS-QOL-J), Pain Catastrophizing Scale (PCS-J), and Visceral Sensitivity Index (VSI-J). A two-way ANOVA was conducted with group (intervention vs. control) and time (pre, mid, post, follow-up 1) as independent variables.
The intervention group used the app for 5–10 minutes daily over two months. The app included three components: psychoeducation, cognitive restructuring, and exposure. Psychoeducation consisted of educational materials and follow-up quizzes. Cognitive restructuring used gamified multiple-choice content (135 items), replacing conventional thought records. Exposure involved users creating individual anxiety hierarchies and recording their thoughts before and after exercises. The app visualized anxiety changes and progress via graphs.

Table 1.
Intervention module of the application

Results

Eleven participants in the intervention group and eight in the control group completed the program. Significant group × time interactions were observed for all outcome measures. For the IBSSI-J, the interaction was significant (F(3, 51) = 4.41, p < .001), with the intervention group showing greater improvement at mid-point (F(1, 17) = 5.54, p = .03, η² = .25). For the IBS-QOL-J, a significant interaction was found (F(3, 51) = 8.00, p < .001), with improvement evident at follow-up 1 (F(1, 17) = 6.65, p = .02, η² = .28). For the PCS-J, the interaction was significant (F(3, 51) = 3.83, p = .02), with improvements at post (F(1, 17) = 9.26, p = .01, η² = .35) and follow-up 1 (F(1, 17) = 5.83, p = .03, η² = .26). For the VSI-J, the interaction also reached significance (F(3, 51) = 3.32, p = .05).

Conclusion

The CBT-based app was effective in reducing IBS symptom severity. Its effects persisted after the intervention and extended to improvements in QOL, visceral anxiety, and pain catastrophizing—psychological factors associated with the maintenance and exacerbation of IBS. It is assumed that the cognitive restructuring component of the app facilitated cognitive diversification among participants. By empirically challenging the plausibility of these diversified cognitions through behavioral experiments in the form of exposure tasks, participants were able to further develop more adaptive thoughts. This process is considered to have contributed to the improvement of symptoms and enhancement of QOL. This digital approach may offer a viable solution to current barriers in CBT access.

Introduction

Functional diseases of the gastrointestinal tract are a common diagnosis, with the most common manifestations being functional dyspepsia and IBS. The pathophysiological mechanisms and etiology of this group of diseases are not fully understood, but stress is believed to play a key role.

Aims & Methods

This study aims to evaluate the effectiveness of a low-histamine diet in patients with irritable bowel syndrome. Patients who meet the ROME IV criteria were included in the study. The study included 120 patients, divided into three groups: low- histamine diet, FODMAP diet and mediterranian diet.Questionnaires were used to assess stress levels PSS-4, anxiety GAD-7, severity of IBS - IBS Severity Score, and quality of life. The questionnaires were completed three times: both at the beginning of the study, immediately after the end of the 4-week diet, and one month after the end of the diet therapy.

Results

The low-histamine diet led to a statistically significant improvement in IBS symptoms compared to baseline. These findings suggest that the dietary intervention had a positive therapeutic effect ( low- histamine diet : t = 9.6181, p-value < 0.001, low FODMAP diet Z = 22, p-value < 0.001, mediterannian diet Z =119, p-value < 0.001).

Conclusion

Dietary therapy plays a key role in the management of IBS. The low-histamine diet shows promising results and may serve as a viable alternative to the FODMAP diet.

Disclosure

The study was launched after receiving approval from the Research Ethics Committee (REC) at the Medical University "Prof. Dr. Paraskev Stoyanov" – Varna, protocol 111/ 20.01.2022y.Data were processed and analyzed using appropriate statistical methods chosen according to the nature of the variables and research questions. The analysis includes:

• Evaluation of the statistical significance of the main and interactions between the factors (Repeated Measures with Wicolxon and Paired t-test).
• Regression analysis to assess relationships between dependent and independent variables. As well as using heteroskedasticity-robust standard error estimates (HC3) to ensure accuracy of regression analysis results.

Introduction

Intestinal ultrasound (IUS) is a non-invasive, reproducible, low-cost technique for the assessment of intestinal diseases.¹
Crohn's disease (CD) and irritable bowel syndrome (IBS) are two of the major causes of chronic diarrhoea and abdominal pain in high-income countries.² IBS, especially in the diarrheal (IBS-D) or mixed (IBS-M) variants, has clinical features similar to those of CD.
The role of IUS in the diagnosis and monitoring of CD is well established,^{3, 4} whereas only scanty data are available on IBS. Current IBS guidelines do not recommend the use of IUS even to distinguish between IBS-D or IBS-M and CD.^{5, 6}

Aims & Methods

The aim of this two-gate diagnostic study was to assess the accuracy of IUS in discriminating between IBS-D or IBS-M and CD in patients presenting with similar symptoms.
In a high-volume tertiary Centre, consecutive patients symptomatic for chronic diarrhoea and abdominal pain underwent IUS performed by three experienced gastroenterologists.
In the group with clinically active CD, patients had a previous diagnosis based on clinical, biochemical, endoscopic, radiologic and histologic criteria, while in the IBS group subjects had a previous diagnosis based on Rome IV Criteria.
Bowel wall thickness (BWT) of the terminal ileum, ascending colon, transverse colon and descending colon/sigma was evaluated using two cut-offs of 3 mm and 4 mm.⁷ Enlarged lymph nodes, mesenteric fat hypertrophy, bowel wall stratification and submucosal vascularity were also assessed.
The diagnostic accuracy of IUS in discriminating between the two groups was estimated in terms of sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-) and overall accuracy (OA) (Table 1).

Results

A total of 50 patients with IBS (62% female, mean age 41 years, SD ± 13 years, 54% IBS-D) and 50 subjects with CD (44% female, mean age 47 years, SD ± 17 years) were enrolled.
Forty-nine patients with IBS (98%) and 8 patients with CD (16%) and had a BWT < 3 mm. 49 patient with IBS (98%) and 12 patients with CD (24%) had a BWT < 4 mm.
Sensibility, specificity, LR+ and LR- of BWT < 3 mm were 98%, 84%, 6.13 and 0.02, respectively.
Sensibility, specificity, LR+ and LR- of BWT < 4 mm were 98%, 76%, 4.08 and 0.03, respectively.
BWT with 3 mm and 4 mm cut-offs showed an OA in discriminating between CD and IBS-D or IBS-M of 91% and 87%.
The absence of altered IUS parameters had 94% OA in discriminating between CD and IBS (Table 1).

Conclusion

IUS seems able to discriminate between IBS-D or IBS-M and CD in patients with chronic diarrhoea and abdominal pain. Particularly, a BWT < 3 mm may rule out the presence of clinically active CD and support the diagnosis of IBS. On the other hand, a BWT > 3 mm or a single altered ultrasound parameter might raise suspicion of CD and justify further testing. Cross-sectional studies are needed to confirm these preliminary results.

References

[1] Bryant RV, et al. Gastrointestinal ultrasound in inflammatory bowel disease: an underused resource with potential paradigm-changing application. Gut 2018;67(May (5)):973–85.
[2] Arasaradnam TP, et al. Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology, 3rd edition. Gut vol. 67,8 (2018): 1380-1399.
[3] Castiglione F, et al. Noninvasive diagnosis of small bowel Crohn’s disease: direct comparison of bowel sonography and magnetic resonance enterography. Inflamm Bowel Dis 2013;19:991–8.
[4] Maaser C et al. ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 1: Initial diagnosis, monitoring of known IBD, detection of complications. Journal of Crohn's & colitis vol. 13,2 (2019): 144-164.
[5] Vasant, Dipesh H et al. British Society of Gastroenterology guidelines on the management of irritable bowel syndrome. Gut vol. 70,7 (2021): 1214-1240.
[6] Savarino E et al. “Functional bowel disorders with diarrhoea: Clinical guidelines of the United European Gastroenterology and European Society for Neurogastroenterology and Motility.” United European gastroenterology journal vol. 10,6 (2022): 556-584.
[7] Fraquelli M, et al. Role of US in detection of Crohn disease: meta-analysis. Radiology. 2005;236(1):95-101.

Introduction

Irritable bowel syndrome is one of the most common Disorders of gut-brain interaction, with diarrhea being the predominant subtype. At present, there are limited drugs for effective management of irritable bowel syndrome.
Compound glutamine entersoluble capsules are composed of traditional chinese medicine formulas Sijunzi Tang and L-glutamine. The Sijunzi Tang, which has been used in traditional complementary and alternative integrated medicine, has been used for the treatment of irritable bowel syndrome for many years. However, there is a lack of evidence from modern evidence-based medicine, its clinical efficacy and safety need to be confirmed. L-glutamine has the function of repairing damaged intestinal mucosa.

Aims & Methods

This study performed a multicenter randomized double-blind placebo-controlled withdrawal trial to explore the effectiveness and safety of compound glutamine entersoluble capsules in the treatment of diarrhea predominant irritable bowel syndrome.
The selected participants received the investigational drug for four weeks during the first single arm stage. The responding participants were randomly assigned to the compound glutamine entersoluble capsules and placebo groups in a 1:1 ratio for another 4 weeks.
The primary efficacy endpoint of the study was the response rate of both the improvement in abdominal pain and bowel movements after treatment in randomized controlled trial subjects (50% of the treatment course met the requirement of at least 30% improvement in abdominal pain severity (NRS pain score) and a reduction of at least 50% in bowel movement days for Bristol 6 or 7 types).

Results

A total of 558 subjects in 22 centers, of which 493 subjects were successfully screened and entered the placebo introduction period. During the placebo introduction period, there were a total of 493 subjects, of which 481 subjects were successfully rescreened and entered the single arm period. 437 subjects entered the randomized controlled trial period and were randomly divided into a treatment group of 217 subjects and a placebo group of 220 subjects.
For the primary efficacy endpoint, the number of response cases in the experimental group and placebo group were 114 (54.55%) and 89 (41.20%), respectively (P=0.0059). For secondary efficacy endpoints: (1) The number of improvements in NRS pain scores in the experimental group and placebo group were 138 (66.03%) and 107 (49.54%), respectively (P=0.0006); (2) The number of improved bowel movements in the experimental group and placebo group were 157 (75.12%) and 118 (54.63%), respectively (P<0.0001); (3) The median (quartile) relative baseline change of IBS-SSS scale in the experimental group was -47.00 (-97.00, -14.00) points; The median (quartile) relative baseline change in the placebo group was -17.00 (-63.00, 16.00) points, and there was a statistically significant difference between the two groups (P<0.0001); (4) The median (quartile) relative baseline change of IBS-QOL in the experimental group was -11.46 (-43.01, 0.00) points; The median (quartile) relative baseline change in the placebo group was -3.57 (-39.43,0.00) points (P=0.0007).
During the randomized controlled trial period, the incidence of all adverse events in the 217 subjects in the trial group was 18.89%, the placebo group was 22.27%, the incidence of TEAEs related to the drug in the trial group was 2.30%, and the placebo group was 3.18%.

Conclusion

Compound glutamine entersoluble capsule can effectively improve the clinical symptoms of diarrhea predominant irritable bowel syndrome with a satisfactory safety.

Introduction

Irritable bowel syndrome (IBS) is among the most prevalent gastrointestinal conditions. However, its therapeutic management poses challenges, with many current recommendations resting on a low level of evidence.

Aims & Methods

Our objective is to conduct a systematic review with meta-analysis of randomized, double-blind, placebo-controlled trials to assess the efficacy of antidepressants in treating IBS. ​
Systematic review with meta-analysis performed according to PRISMA guidelines and registered on the PROSPERO platform (CRD42024502427). PubMed, EMBASE, and The Cochrane Library platforms were searched from inception to January 2024. Only randomized, double-blind, placebo-controlled trials, conducted in patients with IBS patients, with a minimum treatment period of 4 weeks, were included. The quality of evidence was assessed using the revised version of the Cochrane tool (RoB 2). A random-effects model was used. Heterogeneity was assessed by the I² statistics. Funnel plots and the Egger test were used to assess publication bias. Statistical analysis was performed using STATA v16.

Results

The search strategy identified 1340 studies, of which 16 were included, totaling 1428 patients. Among these studies, 733 patients were assigned to the antidepressant group and 698 to the placebo group. In the intervention group, 405 (55.3%) patients reported improvement, compared to only 227 (32.5%) patients in the placebo group. The meta-analysis showed that the use of antidepressants in patients with IBS provides a benefit in overall symptom improvement (OR=3.02; 95% CI 2.16-4.2) compared to placebo.
A subgroup analysis of 9 studies, comprising 1008 patients, assessed the efficacy of tricyclic antidepressants (TCAs) in the same setting and revealed similar results (OR=3.39, 95% CI 2.24-5.12), as did the sub-analysis of 6 studies (including 363 patients) evaluating the efficacy of selective serotonin reuptake inhibitors (SSRIs) (OR= OR=2.39, 95% CI 1.14-5.01). The efficacy also extends to patients refractory to first-line measures (6 studies including 713 patients) (OR=2.96, 95% CI 1.67-5.25) and to patients without psychopathology (8 studies including 471 patients) (OR=2.92, 95% CI 1.6-5.31). Concerning symptoms, a sub analysis also confirmed the efficacy of antidepressants specifically both in the improvement of abdominal pain (OR=4.33, 95% CI 2.1-8.93) and in abdominal distension (OR=2.68, 95% CI 1.42-5.04).
Only in the sub-analysis assessing the efficacy of SSRIs and of the improvement of abdominal pain, I² was slightly >60%, indicating substantial heterogeneity, but <75%. Causes of heterogeneity were searched. Publication bias was detected, and potential sources were identified. Sub-analysis without the studies identified as sources of this bias revealed similar results with lower heterogeneity.

Conclusion

Antidepressants, including both TCAs and SSRIs, demonstrate efficacy in patients with IBS, presenting a validated treatment option supported by evidence. Moreover, these medications can be beneficial to patients resistant to initial treatments and those lacking psychopathological symptoms.

References

Drossman DA, Tack J, Ford AC, Szigethy E, Törnblom H, Van Oudenhove L. Neuromodulators for Functional Gastrointestinal Disorders (Disorders of Gut−Brain Interaction): A Rome Foundation Working Team Report. Gastroenterology 2018;154:1140-1171.e1. https://doi.org/10.1053/j.gastro.2017.11.279.
Lacy BE, Pimentel M, Brenner DM, Chey WD, Keefer LA, Long MD, et al. ACG Clinical Guideline: Management of Irritable Bowel Syndrome. Am J Gastroenterol 2021;116:17–44. https://doi.org/10.14309/ajg.0000000000001036.
Lovell RM, Ford AC. Global Prevalence of and Risk Factors for Irritable Bowel Syndrome: A Meta-analysis. Clin Gastroenterol Hepatol 2012;10:712-721.e4. https://doi.org/10.1016/j.cgh.2012.02.029.
Vasant DH, Paine PA, Black CJ, Houghton LA, Everitt HA, Corsetti M, et al. British Society of Gastroenterology guidelines on the management of irritable bowel syndrome. Gut 2021;70:1214–40. https://doi.org/10.1136/gutjnl-2021-324598.

Disclosure

FP received speaker fees from Abbvie, Falk, Ferring, Janssen, Pfizer, Pharmakern, Takeda and Tillotts. The other authors have no conflict of interest.