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Introduction

Chronic pancreatitis is one of the well-known risk factors of pancreatic adenocarcinoma, the 4th leading cause of cancer mortality. Excessive chronic alcohol consumption is the first cause leading to chronic pancreatic and hepatic inflammation. The intestinal microbiota plays a role in the pathogenesis of these two diseases and patients with chronic alcoholic pancreatitis (CAP) or alcoholic hepatitis (AH) display altered and specific gut dysbiosis, with a higher relative abundance of Enterococcus in patients with CAP compared to AH(1). A recent study identified strains of E. faecalis able to produce a toxin, called cytolysin, responsible for liver lesions in chronic liver diseases. Its presence was associated with the worst clinical outcomes(2). It is yet unknown whether patients with CAP also exhibit an elevated relative abundance of cytolysin-producing E. faecalis strains.

Aims & Methods

The objectives of this study were 1/ to assess the presence of E. faecalis strains expressing or not cytolysin, in the intestinal microbiota of patients with CAP (n = 24) compared to patients with AH (n = 27) and to healthy controls (HC, n = 28), 2/ to evaluate the role of E. faecalis strains (isolated from the patients), in the genesis and potentiation of pancreatitis lesions and early precancerous lesions (acinar-to-ductal metaplasia), in a murine model of pancreatitis induced by cerulein, and 3/ to assess the presence of Enterococcus in surgical specimens of patients who went under pancreatic resection for CAP, (n = 6) compared to controls (normal pancreatic parenchyma apart of benign tumors n = 4).

Results

Our data showed that the relative abundance of cytolysin-positive E. faecalis in the intestinal microbiota is elevated in patients with AH and even more in patients with CAP. Genomic DNA of E. faecalis was detected in 96% of CAP patients, and 85% of AH patients. CAP patients were more frequently cytolysin-positive (96%) than HC (39%, p < 0.001) or AH patients (48%, p < 0.001). The relative abundance of cytolysin-positive E. faecalis was elevated in CAP and AH patients (p = 0.0006 and p= 0.0067) but not HC. In our murine model of cerulein-induced chronic pancreatitis, E. faecalis tend to increase the rate of pancreatitis lesions, as well as the number of acinar-to-ductal metaplasia lesions, specifically when pancreatitis is triggered. We used two different anti-Enterococcus antibodies with concordant results, showing that Enterococcus is present in the pancreatic parenchyma of patients with CAP, but not in the healthy pancreas of controls.

Conclusion

These results support a potentially detrimental role of Enterococcus, and especially E. faecalis, in the evolution of pancreatic inflammation. This study opens new research perspectives to investigate the pathophysiological mechanisms of intestinal microbiota species in the pancreatic exocrine tissue. Microbiota and metabolites produced by these microorganisms (like cytolysin) are probably key actors in the pancreatic inflammation process, involved in the cross-talk between the gut and pancreas. It could lead to consider potential new therapeutic targets in patients with chronic pancreatitis at risk of developing aggressive pancreatic cancers.

References

1. Ciocan D, Rebours V, Voican CS, Wrzosek L, Puchois V, Cassard AM, et al. Characterization of intestinal microbiota in alcoholic patients with and without alcoholic hepatitis or chronic alcoholic pancreatitis. Sci Rep. 19 mars 2018;8(1):4822.
2. Duan Y, Llorente C, Lang S, Brandl K, Chu H, Jiang L, et al. Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease. Nature. nov 2019;575(7783):505‑11.

ENTEROCOCCUS FAECALIS IS INVOLVED IN THE PANCREATITIS PROCESS

CLEMENCE DESCOURVIERES 1, Dragos Ciocan 2, Cristel Archambaud 3, Anne Couvelard 4, Clara Perrin 5, Pascale Serror 3, Cosmin Sebastian Voican 5, Nicolas Trainel 6, Anais Chassac 7, Aurélie Bobillot 3, Gabriel Perlemuter 8, Anne Marie Cassard 9, Vinciane Rebours 10

1 INSERM 1149, Centre de recherche pour l’inflammation (CRI), Paris-Cité University, Paris, France|||Pathology Department, Bichat Hospital, APHP, Paris-Cité University, Paris, France|||Université Paris-Saclay, Inserm U996, Inflammation, Microbiome and Immun

2 Antoine Beclere Hospital, Paris, France|||Université Paris-Saclay, Inserm U996, Inflammation, Microbiome and Immunosurveillance, Orsay, France|||Systems Immunology Department, Weizmann Institute of Science, Rehovot, Israel

3 Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, France

4 Pathology Department, Bichat Hospital, APHP, Paris-Cité University, Paris, France|||INSERM 1149, Centre de recherche pour l’inflammation (CRI), Paris-Cité University, Paris, France

5 Antoine Beclere Hospital, Paris, France|||Université Paris-Saclay, Inserm U996, Inflammation, Microbiome and Immunosurveillance, Orsay, France

6 Université Paris-Saclay, Inserm U996, Inflammation, Microbiome and Immunosurveillance, Orsay, France

7 Pathology Department, Bichat Hospital, APHP, Paris-Cité University, Paris, France

8 Antoine Beclere Hospital, Paris, France|||Université Paris-Saclay, Inserm U996, Inflammation, Microbiome and Immunosurveillance, Orsay, France|||Paris Center for Microbiome Medicine (PaCeMM) FHU, Paris, France

9 Université Paris-Saclay, Inserm U996, Inflammation, Microbiome and Immunosurveillance, Orsay, France|||Paris Center for Microbiome Medicine (PaCeMM) FHU, Paris, France

10 INSERM 1149, Centre de recherche pour l’inflammation (CRI), Paris-Cité University, Paris, France|||Hopital Beaujon, Clichy, France

Conference

UEG Week Copenhagen 2023

Topics

Pancreas

Submission format

Abstract

Session

PP 08 Pancreas (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

UEG Online Course

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Bowel function is significantly affected after rectal surgery. While sphincter-preserving techniques aim to maintain anal continence, many patients experience a spectrum of bowel dysfunction, collectively known as Low Anterior Resection Syndrome (LARS). LARS includes symptoms such as incontinence, constipation, urgency, and stool clustering, which can severely impact a patient’s quality of life. The prevalence of LARS is alarmingly high, affecting a majority of patients, and symptoms can persist for years after surgical treatment.

Target audience

Gastroenterologists
Colorectal surgeons
Oncologists
Nurses/Stoma therapists
Primary care physicians

Consequences of proctology surgery (LARS)

Harald Rosen, Andreas Rink, Peter Christensen, Franco Marinello

Event

Consequences of proctology surgery (LARS)

Topics

Surgery

Accreditation status

accredited

Duration

1 hour

Published

2026

UEG Podcast Episode

Journal Podcast

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UEG Journal Best Paper Award 2022 - Combining biologics and small molecules in IBD

Katarzyna Pawlak 1, Laurent Goessens 2

1 Department Gastroenterology, Endoscopy Unit, Hospital of the Ministry of Interior and Administration, Szczecin, Poland

2 Centre Hospitalier de Mouscron, Belgium

Topics

IBD

Published

2022

UEG Online Course

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This course builds on foundational concepts to examine contemporary mechanisms driving GORD phenotypes. We revisit key epidemiological and clinical distinctions before exploring gastric physiology, including postprandial acid–bile dynamics, H. pylori-related acid output, motility patterns, obesity-related changes, and post-surgical anatomy. Oesophagogastric junction competence (LES pressure, TLESRs, hiatal hernia) and refluxate characteristics (acidic to gaseous; PPI-modified) are discussed with emphasis on symptom generation. We detail epithelial biology, micro- and macroinflammatory responses across NERD and erosive disease, and advances in nociceptive signalling, receptor expression, central modulation, and hypervigilance. Key clinical studies, cytokine-driven pathways, and emerging therapeutic approaches are highlighted. The course concludes with implications for diagnosis, phenotype-guided management, and outstanding research questions.

GORD Pathophysiology - Part 2

Edoardo Savarino, Ahsen Ustaoglu

Event

GORD Pathophysiology Part 2

Topics

Neurogastroenterology & Motility

Accreditation status

accredited

Duration

1 hour

Published

2026

UEG Online Course

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About this online course

Stem cells are primitive and undifferentiated cells in human tissues (foetal and adult) with self-renewal, multipotency and longevity properties. They are responsible for cellular regeneration within the gastrointestinal tract but also play an essential role in different GI pathologies (e.g., Barrett’s oesophagus).

A gastroenterologist’s guide to stem cells, by Simon Leedham and Stuart McDonalds, covers the basic definitions of stem cells and their different locations in the gastrointestinal tract, homeostasis, the role of stem cells in intestinal regeneration, metaplasia, and tumour heterogeneity. The course includes comprehensive PPT slides, and bespoke video presentations filmed in London in December 2022. Figures, schemes, and further readings are included for consideration. The combined material has a total duration of approximately 60 minutes. The estimated time needed to complete the course, including the final assessment, is 60 minutes.

Target audience

This course is suitable for gastroenterologists in training, but is also appropriate for nurses, basic scientist in gastroenterology, medical students with interest in gastroenterology as well as other physicians (oncology, regenerative medicine, research).

Gastroenterologist's guide to stem cells

Simon Leedham, Stuart McDonald

Event

Gastroenterologist's guide to stem cells

Accreditation status

accredited

Duration

1 hour

Published

2024

UEG Online Course

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Modern guideline development has evolved over the last 20 years to improve quality of clinical guidelines.

This course aims to provide basic knowledge of developing guidelines. It will explain the process of how to go about writing protocol, the very basics regarding GRADE, and what you need to do after completing a guideline. It will also signpost you to other courses organised by Guideline International Network.

The course includes comprehensive PPT slides and bespoke video presentations. The combined material has a total duration of approximately 30 minutes. The estimated time needed to complete the course, including the final assessment, is 45 minutes.

Target audience

This course is suitable for gastroenterologists in training, but is also appropriate for physicians in other disciplines and surgeons , as well as nurses, biotechnicians and advanced-years’ medical students who have an interest in developing guidelines.

Enrol Part 2: How to develop guidelines - Part 2

How to develop guidelines - Part 1

Yasuko Maeda, Adele Sayers, Ana Dugic

Event

How to develop guidelines - Part 1

Topics

Education & Training

Accreditation status

accredited

Duration

45 minutes

Published

2024

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Introduction

Dysfunctional and leaky gut barrier are characteristics of cirrhosis and associated with disease progression and mortality. Utility of biomarkers, indicating the presence and extent of intestinal barrier dysfunction, remains a controversial issue in the prognosis and risk stratification of decompensated cirrhosis. Villin-1 (VIL1) is an actin-bundling protein, present in the intestinal, renal and biliary brush border. VIL1 is downregulated in response to chronic injury and diverse cellular stressors, including the microbiome, while during acute stress it is redistributed from the brush border to the basolateral membrane, which facilitates its release into the blood.

Aims & Methods

We investigated clinical significance of serum VIL1 levels in patients with cirrhosis and acute decompensation (AD).Patients (n = 86) and healthy controls (HC; n = 50) from the MICROB-PREDICT cohort were tested for serum VIL1 by ELISA. Four patient severity sub-groups were defined according to the PREDICT study (stable AD (SDC), unstable AD (UDC), pre-ACLF and ACLF [acute-on-chronic liver failure]). VIL1 immunohistochemistry (IHC) evaluation of duodenum biopsy was performed in a sub-cohort of the patients (n = 13) and controls (n = 11).

Results

Serum VIL1 levels were decreased in SDC patients (median [IQR]: 6.5 [4.9-10.4] vs 12 [8.4-14.9] ng/mL, p < 0.001) compared to controls and increased in more severe disease. This difference was confirmed in duodenum tissue by IHC. Significantly higher serum VIL1 levels were detected in pre-ACLF patients compared to those who did not develop ACLF (10.7 [7.8-22.9] vs 6.9 [5.0-10.5] ng/mL, p = 0.004), while in ACLF survivors decreased VIL1 levels were observed on day-7 compared to day-0 (9.8 [7.3-14.6] vs 12.7 [9.7-18.1] ng/mL, p = 0.010). High serum VIL1 levels (≥16.17 ng/mL) predicted 90-day mortality (AUROC:0.73, 95%CI: 0.563-0.888, p = 0.013) and in combination with high (≥ 50) CLIF-C AD score the prediction accuracy was excellent (both is high: 75%; all other together: 8% mortality, LogRank p < 0.001). High serum VIL1 level was able to predict mortality both in the presence (20% vs 62% LogRank p = 0.030) and absence (14% vs 40% LogRank p = 0.008) of renal failure.

Conclusion

Besides the six organ failures included in CLIF-SOFA, patients with cirrhosis and AD may also develop intestinal failure, as an additional organ failure. Serum VIL1 level could reliably indicate this organ failure and made the mortality risk stratification performed by CLIF-C OF score more accurate.

Disclosure

The MICROB-PREDICT project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 825694

SERUM VILLIN-1 LEVEL – A TELL-TALE SIGN OF GUT BARRIER FAILURE IN CIRRHOTIC PATIENTS WITH ACUTE DECOMPENSATION

David Tornai 1, Boglarka Balogh 1, Aniko Csillag 1, Andras Budai 2, Andras Kiss 2, Tamas Dinya 1, Gabor Mehes 1, Lukacs Barath 1, István Tornai 1, Zsuzsanna Vitális 1, Nora Sipeki 1, Tamás Tornai 3, Peter Antal-Szalmas 1, Jonel Trebicka 4, Mária Papp 1

1 University of Debrecen, Faculty of Medicine, Debrecen, Hungary

2 Semmelweis University, Faculty of Medicine, Budapest, Hungary

3 Semmelweis University, Budapest, Hungary

4 University of Münster, Münster, Germany|||European Foundation for Study of Chronic Liver Failure, Barcelona, Spain

Conference

UEG Week Copenhagen 2023

Topics

Hepatobiliary

Submission format

Abstract

Session

Liver and biliary: Clinical aspects (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

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