Introduction

Many irritable bowel syndrome (IBS) patients report gastrointestinal (GI) symptoms due to various foods, resulting in food avoidance. However, a detailed description of trigger foods and related GI symptoms and avoidance behaviour is lacking. Therefore, we evaluated the extent and nature of food intolerance and avoidance in IBS patients, and its relation to GI symptoms and psychological comorbidities.

Aims & Methods

Food intolerance and avoidance behaviour were evaluated in 124 IBS patients and 113 healthy controls (HC) using a questionnaire with 257 food products of 13 food groups. Per product, participants were asked if they experience symptoms (i.e. nausea, constipation, diarrhoea, bloating, abdominal pain) after consumption, and if they consumed this product despite these symptoms. Furthermore, IBS symptom severity and psychological factors were assessed.

Results

IBS patients reported a higher number of food products with perceived intolerance than HC (median of 18.0 (25^th-75^th percentile 10.0-33.5) vs 1.0 (0.0-8.0), p<0.001). A wide variety of trigger foods was reported, with gas-producing foods and fatty/cream-based dairy products most frequently reported by both groups. Predominant symptoms were abdominal pain and bloating. The number of avoided foods was higher in IBS (15.0 (8.0-27.0) vs 1.0 (0.0-7.0), p<0.001). Food avoidance was not significantly related to symptom type, but was associated with an IBS diagnosis, female sex, and higher screening scores for somatisation and Avoidant/Restrictive Food Intake Disorder.

Conclusion

Self-reported food intolerance and avoidance is higher in IBS than HC, with a wide variety of trigger foods. Food avoidance was significantly related to psychological factors, but not to symptom type. This warrants individual dietary guidance, as well as attention for psychological factors.

Disclosure

D Keszthelyi: DK reports receiving research funding from ZonMw, MLDS, UEG, Rome Foundation, Horizon Europe, Horizon 2020, Grunenthal, Allergan and speaker’s fee from Dr Falk (paid to host institute).
DMAE Jonkers: DMAEJ reports receiving a public–private partnership grant of TKI Well on Wheat? and TKI grants from Agri & Food and Health Holland, the Carbokinetics programme as part of the Netherlands Organisation for Scientific Research–Carbohydrate Competence Center partnership, Organic A2BV/Mothersfinest, and Horizon 2020.

Introduction

Recent years have seen a significant increase in randomized controlled trials (RCT) published on the efficacy of probiotics on irritable bowel syndrome (IBS), which several reviews have tried to comprehensively review. Two recent trials, Yang et al. 2024¹ and Chen et al. 2023² report the safety and efficacy of probiotics for IBS, which seems to reflect prevailing favorable view of this therapeutic option by most reviews conducted. Yet, despite efforts in this field, major organizations have not changed their stance in this and make no assertive recommendation for probiotics in afflicted patients^3,4. While further investigations are required, two challenges are faced: (1) repeated reviews have been undertaken in this field, resulting in a "multiplicity problem", (2) traditional meta-analytic techniques may also fail to provide a conclusive answer on the sufficiency of evidence, particularly when the data are sparse, and the risk of type I and type II errors is significant. This indicates a need for.

Aims & Methods

This study aims to evaluate the efficacy of probiotics in alleviating symptoms of IBS and improve quality of life through a timely implemented trial sequential analysis (TSA) and rigorously evaluate the evidence for recommendations on future studies. Medline, Embase, Web of Science, and Cochrane were screened for randomized controlled trials (RCTs) comparing probiotics to placebo in adult patients with IBS. Primary outcomes included IBS Symptom Severity Score (IBS-SSS) and IBS Quality of Life (IBS-QOL) scores comparing probiotics and placebo groups. Traditional pairwise meta-analysis conducted in restricted maximum likelihood was conducted, with subsequent TSA . Study quality was graded according to risk-of-bias 2 (ROB-2) and certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE).

Results

42 studies were included. Overall, probiotics demonstrated non-significant improvements in IBS-SSS (MD: -27.64; 95% CI: -56.90 to 1.63; p=0.06) and IBS-QOL (MD: 1.33; 95% CI: -3.65 to 6.30; p=0.59). TSA was conducted on IBS-SSS demonstrated current evidence has not reached the required information size. The representative cumulative Z-curve demonstrated neither futility, benefit nor detrimental effect, indicating the need for further trials. Assessment with ROB-2 indicates high quality amongst most trials included in this study. GRADE evaluation of the evidence demonstrated low certainty of existing evidence.

Table 1: GRADE Evaluation

No. of studies	Study design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Probiotics	Placebo	Relative (95% CI)	Absolute (95% CI)	Certainty
Probiotics effectively reduces a patient's IBS-SSS score
24	randomised trials	not seriousa	very seriousb	not serious	very seriousc	publication bias strongly suspectedd	2237	1599	-	MD 27.64 lower (56.9 lower to 1.63 higher)	⨁◯◯◯ Very lowa,b,c,d
Probiotics effectively reduces a patient's IBS-QOL score
24	randomised trials	not seriousa	very seriousb	not serious	not seriouse	publication bias strongly suspectedd	2292	1712	-	MD 1.33 higher (3.65 lower to 6.3 higher)	⨁◯◯◯ Very lowa,b,d,e

CI: confidence interval; MD: mean difference

Two contributing factors to the low certainty of current evidence include: (1) Inconsistency of existing trials – there exists high level of heterogeneity as detected by statistical analysis through I² and Cochran Q amongst studies; (2) Suspected publication bias through inspection of a funnel plot, though Egger’s regression did not demonstrate statistical significance.

Conclusion

Existing evidence is insufficient to make conclusive recommendations regarding the role probiotics should play in the management of IBS in symptoms and QOL. Given the persistent heterogeneity and potential publication bias, future research should focus on standardizing probiotic interventions and clarifying their clinical utility to truly advance the field.

References

1. Yang R, Jiang J, Ouyang J, Zhao Y, Xi B. Efficacy and safety of probiotics in irritable bowel syndrome: a systematic review and meta-analysis. Clinical Nutrition ESPEN. 2024;
2. Chen M, Yuan L, Xie C-R, et al. Probiotics for the management of irritable bowel syndrome: a systematic review and three-level meta-analysis. International Journal of Surgery. 2023;109(11):3631-3647.
3. Su GL, Ko CW, Bercik P, et al. AGA Clinical Practice Guidelines on the Role of Probiotics in the Management of Gastrointestinal Disorders. Gastroenterology. 2020;159(2):697-705. doi:10.1053/j.gastro.2020.05.059
4. McKenzie Y, Thompson J, Gulia P, Lomer M. British Dietetic Association systematic review of systematic reviews and evidence‐based practice guidelines for the use of probiotics in the management of irritable bowel syndrome in adults (2016 update). Journal of Human Nutrition and Dietetics. 2016;29(5):576-592.
5. Lacy BE, Pimentel M, Brenner DM, et al. ACG clinical guideline: management of irritable bowel syndrome. Official journal of the American College of Gastroenterology| ACG. 2021;116(1):17-44.

Disclosure

All authors of the manuscript do not have a conflict of interest to declare.

Introduction

The DOMINO diet app (diet) provides superior symptom relief to a spasmolytic agent (otilonium bromide, OB) in primary care Irritable Bowel Syndrome (IBS)¹. While the DOMINO diet aimed to provide a practical approach to lower intake of FODMAPs (fermentable oligo-, di-, monosaccharides and polyols), genetic polymorphisms in the eosinophil trafficking chemokine receptor CCR3 were associated with response to the diet². A correlation between fecal eosinophil-derived neurotoxin (F-EDN) and colonic mucosal eosinophil degranulation was previously reported in IBS³.

Aims & Methods

To assess a role for eosinophil-driven mucosal inflammation as a target for IBS therapy, we assessed changes in F-EDN levels in primary care patients treated with the DOMINO diet and OB, and their correlation with symptoms and inflammatory markers. In the DOMINO study, primary care physician-diagnosed IBS patients (70% fulfilling Rome IV, Rome+) were randomized to diet or OB. Analysis of gene polymorphisms, blood and stool samples were collected from 356 patients (86 IBS-C, 116 IBS-D, and 154 IBS-M) before and after treatment with diet and OB (respectively n=147 and 163). We compared and correlated F-EDN levels, demographic parameters, IBS symptom severity scoring (IBS-SSS), laboratory blood tests as well as biomarkers of inflammation in stool (secretory Ig/sIgA, Beta-defensin2, calprotectin). Statistical analysis was conducted using non-parametric tests; data were presented as median with interquartile range.

Results

Baseline F-EDN correlated negatively with presence of CCR3 polymorphism (r=-0.13, p=0.02), positively with sIgA (r=0.27, p<0.0001), but showed no significant associations with IBS-SSS scores or other stool parameters. Furthermore, a positive correlation was observed between F-EDN and glucose (r=0.16, p=0.004), insulin (r=0.14, p=0.01) and triglyceride (r=0.12, p=0.03) plasma levels and body weight (r=0.16/p=0.002). F-EDN decreased significantly in responders to the diet (≥50-point improvement on IBS-SSS) (n=104, 0.44μg/g[0.16;0.88] vs. 0.32μg/g[0.15;0.72], p=0.03), but not to medication (n=97, 0.48μg/g[0.16;1.01] vs. 0.44μg/g[0.19;0.87], p=0.57). In diet responders, baseline F-EDN levels correlated positively with calprotectin and sIgA (respectively r=0.24, p=0.01 and r=0.37, p<0.001). The significant decrease in F-EDN after diet was more pronounced in the subset of patients fulfilling Rome IV criteria (n=86, 0.47μg/g[0.17;0.91] vs. 0.34μg/g[0.16;0.75], p=0.02). Baseline F-EDN levels in this cohort correlated with the improvement in IBS-SSS (r=0.21, p=0.04).

Conclusion

In primary care IBS, response to the DOMINO diet, but not to OB, is associated with the presence and decrease of eosinophil-driven intestinal immune activation. Further research will focus on the ability of the DOMINO diet, besides its FODMAP-lowering properties, to improve atypical food allergic reactions involved in IBS pathophysiology.

References

1. Carbone, Van den Houte et al. Gut. 2022
2. Balsiger et al. Gut. 2023
3. Casado-Bedmar et al. Journal of Leukocyte Biology. 2022

Introduction

The protocol of the clinical trial OLGA (Operative Link for Gastritis Assessment) proposed in 2005 (M.Rugge & R. Genta, 2005) has become widely used in clinical practice as the method of unified assessment of the progression of atrophic gastritis and the risk of developing stomach cancer.
The protocol involves obtaining 5 fragments of the gastric mucosa: 2 fragments from the antrum, 2 fragments from the oxyntic part and 1 fragment from the incisura angularis. It was believed that the mucosa in this region, being in fact a transition zone between the location of the pyloric and oxyntic glands of the stomach, may be the place with the most pronounced probability of developing atrophic and dysplastic processes.
The purpose of this study was to establish the significance of histological changes in the gastric mucosa in the region of the incisura angularis to assess the degree of inflammation activity and the stage of atrophic gastritis.

Aims & Methods

1146 patients (916 women and 230 men) with clinical manifestations of chronic gastritis aged 20 to 84 years were examined. Most patients were represented in the age group from 50 to 70 years (54.6%). Biopsy material was obtained during endoscopic examination in accordance with the OLGA protocol. Histological assessment of the degree of inflammation activity and the stage of atrophy was carried out according to the standard OLGA protocol. Then the same samples were evaluated without taking into account histological changes in the incisura angularis.

Results

During histological examination more frequently (73.2%) was detected the mild severity of inflammation in gastric mucosa (grade II according to the OLGA system). This score practically did not change if the biopsy from the incisura angularis was not tested. Severe stages of gastric mucosa atrophy (stages III and IV according to the OLGA system) were detected in 465 patients (40.58%). If changes in the incisura angularis were not taken into account, then severe stages of atrophy (III and IV) were detected in 460 patients (40.1%). In total, changes in the assessment of the stage of atrophy occurred in 53 patients (4.62%), and more often this was observed in patients with stages I and II of atrophy. Only in 8 patients stage IV of atrophy was changed to III, and in 3 patients stage III was changed to stage II. Thus the stage of atrophy was changed in less than 0,5% of patients in groups with severe atrophy if the samples from the incisura angularis were excluded from the examination.

Conclusion

Evaluation of the histological changes in the gastric mucosa from the incisura angularis does not significantly affect the assessment of the grade and stage of chronic gastritis according to the OLGA system.

References

Rugge M, Genta RM. Staging and grading of chronic gastritis. Human Pathology (2005) 36, 228– 233

Disclosure

This study was conducted within the healthcare research project “Epidemiological study of Helicobacter pylori infection prevalence in Moscow” funded by Autonomous non-profit organization "Moscow Center for Innovative Technologies in Healthcare" administered by the Moscow Healthcare Department. Grant No. 0903-1/22.

Introduction

The increasing prevalence of antibiotic resistance and the scarcity of therapeutic options for patients with penicillin allergy have highlighted the necessity for novel treatment regimens. Keverprazan, a novel potassium-competitive acid blocker, provides potent and sustained gastric acid suppression.

Aims & Methods

This study was designed to evaluate the efficacy and safety of keverprazan-minocycline (KM) dual therapy compared with keverprazan-amoxicillin (KA) dual therapy in patients with Helicobacter pylori (H. pylori) infection. From October 2024 to April 2025, a total of 240 patients with H. pylori infection were recruited from six hospitals in Fujian province and randomly assigned to receive either KA dual therapy (amoxicillin 1 g three times daily plus keverprazan 20 mg once daily) or KM dual therapy (minocycline 100 mg twice daily plus keverprazan 20 mg once daily) for a duration of 14 days. The primary endpoint was the H. pylori eradication rate assessed at 4 weeks post-treatment. Secondary endpoints included the symptom relief rate, incidence of adverse events, and patient compliance.

Results

In the intention-to-treat (ITT) analysis, the H. pylori eradication rates were 85.83% (103/120) in the KA group and 87.50% (105/120) in the KM group. In the per-protocol (PP) analysis, the eradication rates were 86.95% (100/115) in the KA group and 90.35% (102/113) in the KM group. No statistically significant differences were observed between the two groups (P = 0.704 for ITT and P = 0.421 for PP analysis). Additionally, symptom remission rates (73.88% vs. 82.50%) and treatment adherence rates (97.01% vs. 97.50%) also showed no significant intergroup differences (both P > 0.05). However, the KM group exhibited a significantly higher overall incidence of adverse events compared with the KA group (38.33% vs. 17.16%, P < 0.001), primarily driven by mild dizziness (25.83% vs. 2.23%, P < 0.001). However, these adverse reactions were mild and did not affect treatment adherence.

Conclusion

The keverprazan-minocycline dual regimen demonstrated high eradication efficacy and acceptable safety in patients with H. pylori infection, with eradication effectiveness comparable to that of the keverprazan-amoxicillin dual therapy and mild adverse reactions. This regimen is recommended for the clinical treatment of H. pylori infection, particularly in patients with penicillin allergy.

Disclosure

There is no conflict of interest.