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How far do we need to investigate?

Chloé Melchior 1

1 Rouen University Hospital, INSERM U1073, CIC-CRB-1404, Rouen, France

Event

UEG Week Berlin 2025

Topics

Primary Care

Session

Bloating

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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GP perspective: How to diagnose, review lifestyle and diet

Jelena Rakic Matic 1

1 Health Care Center Zagreb West, ZAGREB, Croatia

Event

UEG Week Berlin 2025

Topics

Primary Care

Session

Bloating

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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EXOSOMAL CAGA INDUCES MACROPHAGE POLARIZATION AND FERROPTOSIS BY JAK1-2/STAT1 SIGNALING PATHWAY IN HELICOBACTER PYLORI-ASSOCIATED GASTRITIS

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Introduction

Helicobacter pylori (H. pylori) infection is a major cause of gastric diseases, with the virulence factor CagA carried by exosomes playing a crucial role in regulating inflammation. Ferroptosis and M1 polarization are key mechanisms in promoting inflammation, yet the role of CagA in inducing macrophage ferroptosis and M1 polarization to exacerbate gastric mucosal inflammation remains unclear.

Aims & Methods

CagA-positive (CagA+) and CagA-negative (CagA-) H. pylori strains were co-cultured with gastric epithelial cells, and their supernatants were collected. Exosomes were isolated using ultracentrifugation to obtain CagA+Exo and CagA-Exo. Changes in macrophage M1/M2 polarization markers and ferroptosis markers were analyzed under CagA+Exo and CagA-Exo treatment. The activation of the JAK/STAT1 signaling pathway was assessed by Western blot, and STAT1 expression in the nucleus was evaluated using a nuclear protein extraction kit. Chromatin immunoprecipitation (ChIP) was used to identify the binding site of STAT1 on the SLC7A11 promoter. Biopsy samples from the gastric mucosa of gastritis patients infected with CagA+ or CagA- H. pylori were analyzed for macrophage polarization and ferroptosis markers.

Results

Exosomal CagA was found to induce macrophage M1 polarization and ferroptosis, with the ferroptosis inhibitor SLC7A11 playing a key role in CagA-induced ferroptosis. Exosomal CagA activated the JAK/STAT1 signaling pathway, leading to M1 polarization and ferroptosis. Additionally, CagA+Exo increased nuclear STAT1 expression, which subsequently bound to the SLC7A11 promoter to regulate its transcription. In gastric mucosa biopsies from CagA+ H. pylori-infected gastritis patients, increased levels of iNOS (a marker of M1 polarization) and decreased expression of SLC7A11 were observed.

Conclusion

Our findings indicate that exosomal CagA promotes macrophage M1 polarization and ferroptosis through the JAK/STAT1 signaling pathway. This study provides new insights and potential therapeutic targets for H. pylori-associated gastritis.

EXOSOMAL CAGA INDUCES MACROPHAGE POLARIZATION AND FERROPTOSIS BY JAK1-2/STAT1 SIGNALING PATHWAY IN HELICOBACTER PYLORI-ASSOCIATED GASTRITIS

JIAHUI Lin 1, Yuting Liu 1, Tingting Luo 1, Jian Qi 1

1 The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China

Event

UEG Week Berlin 2025

Topics

Mechanisms & Personalised Medicine Stomach & H. Pylori

Submission format

Abstract

Session

H. pylori: Between bench and bedside

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Gut-brain chaos: Here’s how primary care can restore order

Christos D Lionis 1

1 University of Crete, Heraklion, Greece

Event

UEG Week Berlin 2025

Topics

Neurogastroenterology & Motility Paediatrics Standards & Guidelines Stomach & H. Pylori

Session

From guidelines to clinical practice: The gut-brain connection - PPIs and guideline application in clinical practice

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Introduction

Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction affecting 5 to 10% of the population, combining chronic abdominal pain and altered bowel transit. Its varied and complex mechanisms make management difficult and can be responsible for impaired quality of life. Patient education is recommended for managing chronic diseases. As part of a patient education program, the first step is to assess patients' knowledge and needs by conducting a shared educational assessment. Experiments conducted in various countries have shown that therapeutic patient education (TPE) can be effective, reducing severity, improving quality of life, and reducing care seeking. These studies have also shown that patients often have a lack of knowledge and/or misconceptions about IBS (1).

Aims & Methods

This study aimed to assess the baseline knowledge level of patients enrolled in a patient education program. Patients with IBS were selected for participation in a TPE program following a multidisciplinary day hospital for IBS. All patients had to have seen a general practitioner and/or a gastroenterologist outside the team without sufficient improvement in their condition. The TPE was based on a document developed in collaboration with a patient organisation (APSSII). This program was divided into five 1-hour sessions (training and discussion time) conducted by different professionals (neurogastroenterologists, clinical psychologist, dietitian) covering the following points:
1) understanding my illness (epidemiology, diagnosis, mechanisms),
2) talking about my illness and expressing my needs (interaction with loved ones, work, doctor, school, rights and support);
3) organizing my daily life, improving my quality of life (impact of IBS on QoL, work, exercise, intimate life);
4) taking advantage of different treatments and care options (placebo, adverse effects, symptomatic and long-term treatment, alternative treatments);
5) the role of eating and diets (balanced diet, lactose-free, gluten-free, low-FODMAP, food allergies, risks of diets). Before the start of each session, questionnaires testing participants' knowledge on the session topic were completed.

Results

From November 2023 to September 2024, 135 questionnaires completed by 43 patients with IBS were included. 70% were women, mean age 45 ± 18 years, subtypes based on IBS transit: IBS-C 55%, IBS-D 33%, IBS-M 12%, with a mean severity (IBS-SSS) of 331 ± 72 points, EQ5D health score of 50 ± 21. Among the most common misconceptions, 25% believed that a diagnosis by endoscopy was possible, 48% believed the disease could be complicated by IBD, and 13% by colon cancer. Regarding treatments, 11% of patients believed that the placebo effect only concerned medications, 58% believed that faecal microbiota transplantation could currently be offered in clinical routine for IBS care, 78% believed that hypnotherapy was only effective if you believe in it, and 68% believed that multi-strain probiotics were more effective than single-strain ones.

Conclusion

This study, conducted in France on patients with moderate or severe forms of IBS, shows a highly variable level of knowledge about their disease depending on the questions, with some significant misconceptions that need to be addressed. These results justify the implementation of therapeutic education for these patients. A study is underway to verify the improvement in patients' knowledge and the existence of a positive impact of this strategy on symptom severity and quality of life.

References

(1) Halpert et al. What Patients Know About Irritable Bowel Syndrome (IBS) and What They Would Like to Know. National Survey on Patient Educational Needs in IBS and Development and Validation of the Patient Educational Needs Questionnaire (PEQ). Am J Gastroenterol 2007; 102:1972-82.

Disclosure

Nothing to disclose

KNOWLEDGE AND MISCONCEPTIONS OF PATIENTS WITH IRRITABLE BOWEL SYNDROME ENROLLED IN A THERAPEUTIC PATIENT EDUCATION PROGRAM

Fabien Wuestenberghs 1, Pauline Jouet 1, Nicolas Ezratty 1, Ludovic ATTELLY 1, Anne-Sophie Schmitt 1, Mourad Benallaoua 1, Jean-Jacques Raynaud 1, Robert Benamouzig 1, Jean Marc Sabate 1

1 APHP, Avicenne Hospital, Sorbonne Paris Nord University, Bobigny, France

Conference

UEG Week Berlin 2025

Topics

Colorectal

Submission format

Abstract

Session

LOWER GI (Posters)

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Introduction

Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs) have gained attention for their role in managing type 2 diabetes and obesity. These drugs help regulate blood sugar levels and promote satiety. This effect benefits weight management, as it supports better control over eating habits and can lead to significant weight loss in some patients. In addition, recent studies showed promising influences on reducing alcohol consumption.

Aims & Methods

This systematic review assesses the impact of GLP-1 RA treatment on alcohol consumption behaviors. Following PRISMA guidelines, this study is conducted through a comprehensive search in PubMed, EMBASE, Scopus, Cochrane, and ClinicalTrials.gov up to February 1, 2025. It included participants with occasional or excessive alcohol use, focusing on self-reported intake, alcohol-related diagnoses, relapse rates, and neuroimaging. Data extraction and risk-of-bias assessments were independently performed by reviewers using the CASP tool, with both qualitative and quantitative synthesis of outcomes.

Results

Thirteen studies are included in this study with a sample size of 5,246,188 participants. The GLP-1 RAs consisted of Semaglutide, Exenatide, Liraglutide, Dulaglutide, and Tirzepatide. The overall mean alcohol intake decreased significantly from 11.8 ± 1.0 to 4.3 ± 0.5 units per week (p < 0.001) ¹. At week 12, participants in the dulaglutide group consumed approximately 29% less alcohol than those in the placebo group (adjusted relative effect = 0.71, 95% CI 0.52–0.97, P = 0.04) ². In contrast, a randomized controlled trial (RCT) involving Exenatide showed no difference in alcohol consumption (in grams) between the treatment and placebo ³. Additionally, two observational studies reported significant reductions in Alcohol Use Disorders Identification Test (AUDIT) scores with Semaglutide (B = -5.1, SE = 1.3, p < 0.001) and Tirzepatide (B = -6.7, SE = 1.3, p < 0.001) ^4,5. An additional observational study demonstrated a notable decrease in AUDIT-Consumption compared to unexposed individuals (DiD: 0.09 points, 95% CI: 0.03–0.14, p = 0.0025) ⁶. The CASP assessments rated most studies as moderate to high quality.

Study	Key Findings
Hendershot, 2025 and O'Farrell, 2025	Significant reduction in alcohol intake, cravings, and smoking.
Quddos, 2023 and Richards, 2023	GLP-1 RAs reduced alcohol intake, binge drinking, and AUDIT scores.
Andersen, 2022	Varying effects of GLP-1 RA on alcohol-related events over time.
Kalra, 2011	Of 42 participants, 33 showed significant reduction in drinking with 9 abstinences
Probst, 2023	GLP-1 RA reduced alcohol intake compared to placebo.
Qeadan, 2025	GIP/GLP-1 agonists reduced alcohol intoxication in AUD patients.
Kuo, 2025 and Wang, 2024	GLP-1RA reduced recurrent AUD risk.
Farokhnia, 2025	GLP-1RA reduced AUDIT-C scores, more in those with baseline AUD.
E. Jensen, 2024 and Klausen, 2022	Exenatide reduced alcohol consumption, no significant difference from placebo.

Conclusion

GLP-1 receptor agonists appear to offer a promising, effective, and well-tolerated pharmacological approach for reducing alcohol consumption and preventing relapse in alcohol use disorder (AUD). Further large-scale randomized trials are required to confirm their efficacy and guide clinical practice.

References

1. O’Farrell M, Almohaileb FI, le Roux CW. Glucagon-like peptide-1 analogues reduce alcohol intake. Diabetes Obes Metab. 2025;27(3):1601-1604. doi:10.1111/DOM.16152
2. Probst L, Monnerat S, Vogt DR, et al. Effects of dulaglutide on alcohol consumption during smoking cessation. JCI Insight. 2023;8(22). doi:10.1172/JCI.INSIGHT.170419
3. Klausen MK, Jensen ME, Møller M, et al. Exenatide once weekly for alcohol use disorder investigated in a randomized, placebo-controlled clinical trial. JCI Insight. 2022;7(19). doi:10.1172/JCI.INSIGHT.159863
4. Quddos F, Hubshman Z, Tegge A, et al. Semaglutide and Tirzepatide reduce alcohol consumption in individuals with obesity. Scientific Reports 2023 13:1. 2023;13(1):1-12. doi:10.1038/s41598-023-48267-2
5. Richards J, Dorand MF, Royal K, Mnajjed L, Paszkowiak M, Simmons WK. Significant Decrease in Alcohol Use Disorder Symptoms Secondary to Semaglutide Therapy for Weight Loss: A Case Series. J Clin Psychiatry. 2023;85(1). doi:10.4088/JCP.23M15068
6. Farokhnia M, Tazare J, Pince CL, et al. Glucagon-like peptide-1 receptor agonists but not dipeptidyl peptidase-4 inhibitors reduce alcohol intake.

Disclosure

The authors declare no conflicts of interest regarding the publication of this abstract. All findings and conclusions are the authors' own and do not represent the views of any funding organizations or institutions.

GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONIST AND ALCOHOL CONSUMPTION: A SYSTEMATIC REVIEW

Reza Eshraghi 1, Pouya Ebrahimi 2, Raheel Ahmed 3, Delaram Jafarzadeh Ghadimi 4, Kaveh Hosseini 5, Sara Montazeri Namin 6, Ashkan Bahrami 7, Yash Kachela 8, Mohsan Subhani 9, Ali Moradi 10, Farhan Shahid 11

1 Isfahan University of Medical Sciences, Isfahan, Iran, Islamic Republic of

2 Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom

3 Imperial College London, London, United Kingdom

4 Shahid Beheshti University of Medical Sciences, Tehran, Iran, Islamic Republic of

5 Tehran University of Medical Sciences, Tehran, Iran, Islamic Republic of

6 Iran University of Medical Sciences, Tehran, Iran, Islamic Republic of

7 Kashan University of Medical Sciences, Isfahan, Iran, Islamic Republic of

8 Aston University, Birmingham, United Kingdom

9 University Hospitals Nottingham and University of Nottingham, Nottingham, United Kingdom

10 University of South Florida, Florida, United States

11 Queen Elizabeth Hospital, London, United Kingdom

Conference

UEG Week Berlin 2025

Topics

Small Intestine & Nutrition

Submission format

Abstract

Session

Obesity (Posters)

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Introduction

Obesity and type 2 diabetes mellitus (T2DM) represent growing global health challenges, affecting millions of individuals worldwide. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a cornerstone in the management of both conditions due to their metabolic benefits, including weight loss and glycemic control. European cohort studies have reported a high prevalence of gastrointestinal symptoms – including nausea, vomiting and early satiety among patients using GLP-1RAs. In parallel, increased rates of residual gastric content (RGC) during upper endoscopy have raised safety concerns, prompting reevaluation of pre-procedural fasting guidelines. However, data on the effects of GLP1-RA on the gastrointestinal (GI) tract in Asian patients is limited.

Aims & Methods

Our primary aim was to characterize a cohort of patients who received treatment with GLP1-RA in terms of their gastrointestinal side effects and presence of RGC during upper endoscopy. The secondary objective was to compare the afore-mentioned variables between 2 groups: oral versus subcutaneous mode of administration. We conducted a retrospective cross-sectional cohort study of 139 Asian adult patients with T2DM and/or obesity who were prescribed GLP-1RAs at a tertiary hospital between 01 January 2022 to 01 January 2023. Data collected included demographics, anthropometric measurements, co-morbidities, GI symptoms and upper endoscopy findings. Upper endoscopy images were analysed and adequacy of mucosal visibility was graded using the POLPREP scale. Patients were further stratified into two subgroups based on route of GLP-1RA administration: oral versus subcutaneous. Statistical analysis compared symptom prevalence and POLPREP scores across subgroups using chi square test, with p <0.05 considered statistically significant.

Results

A total of 139 patients were analysed. 19.4% of patients had GLP-1RA prescribed for T2DM, 21.6% for Obesity, and 58.8% for both. The most commonly prescribed GLP-1RA was Liraglutide (33.8%) followed by oral Semaglutide (28.1%). Majority of patients (66.9%) did not have any GI side effects. The most commonly reported GI symptoms were abdominal bloating (15.8%), nausea (7.9%) and early satiety (4.3%). 13.7% of patients underwent upper endoscopy with 89.5% having a POLPREP score of 3 with no significant complications reported. None of the patients withheld GLP-1RA prior to endoscopy. Upon stratifying patients based on route of administration, analysis revealed that patients on oral GLP-1RAs were more likely to report nausea compared to those on subcutaneous formulations (15.8% vs 5.0%, p=0.03). There were no significant differences in the other GI symptoms or POLPREP scores.

Conclusion

Based on our Asian cohort, these findings suggest that GLP-1RAs have an acceptable GI symptom profile with a potential route-dependent difference in symptomatology. In addition, discontinuing these drugs prior to upper endoscopy may be unnecessary.

References

1. Camilleri et al. Effects of GLP-1 and other Gut Hormone Receptors on the Gastrointestinal tract and implications in clinical practice. Am J Gastroenterol 2024;119:1028-1037
2. Nadeem et al. Effects of glucagon-like peptide-1 receptor agonists on upper endoscopy in diabetic and nondiabetic patients. Gastrointestinal Endoscopy 2024.
3. Jalleh et al. Gastrointestinal effects of GLP-1 receptor agonists: mechanisms, management, and future directions. Lancet Gastroenterol Hepatol 2024;9:957-64
4. Facciorusso et al. Effects of Glucagon-like peptide-1 receptor agonists on upper gastrointestinal endoscopy: A meta-analysis. Clinical Gastroenterol and Hepatol 2024.
5. Romańczyk et al. Scoring system assessing mucosal visibility of upper gastrointestinal tract: The POLPREP scale. J Gastroenterol Hepatol 2022 Jan;37(1):164-168.