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Appendectomy? The solution for ulcerative colitis

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Appendectomy? The solution for ulcerative colitis

Eva Visser 1

Affiliations

1 Amsterdam University Medical Centre, Amsterdam, Netherlands

Summary

AI Generated

The speaker presented evidence that appendectomy may maintain remission and induce remission in selected patients with ulcerative colitis, with the CURE trial showing a 20% reduction in relapse rates and the COSTA trial demonstrating 33% combined clinical and endoscopic remission in biologic-exposed active UC patients.

The speaker reported that in the CURE randomised controlled trial, appendectomy plus standard therapy was superior to standard therapy alone in maintaining UC remission at one year, with relapse rates reduced by 20% and patients requiring biological agents significantly less often.
The speaker stated that in the COSTA trial of 116 biologic-exposed active UC patients, 33% in the appendectomy group achieved combined clinical and endoscopic remission at 12 months without therapy failure, compared to 12% in the JAK inhibitor group.
The speaker reported that complication rates were very low at 4% in the active UC trial, with only minor complications unrelated to colon activity.
The speaker stated that patients with proctitis or left-sided colitis responded better than those with pancolitis, and appendiceal inflammation or appendix diameter of 6mm or more predicted response to appendectomy.
The speaker noted that median time to response after appendectomy is 12 weeks, which is slower than advanced medical therapies like JAK inhibitors.
The speaker recommended that appendectomy should be discussed earlier in the treatment pathway in collaboration between gastroenterologists and surgeons, not only when colectomy is the last resort.

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Abstract

Event

UEG Week Berlin 2025

Topics

IBD Mechanisms & Personalised Medicine Paediatrics Surgery

Session

What's new in ulcerative colitis 2025?

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Vanessa Stadlbauer

… after ileocecal resection of localised Crohn's disease

Matthieu Allez

LINERIXIBAT SIGNIFICANTLY IMPROVES CHOLESTATIC PRURITUS IN PRIMARY BILIARY CHOLANGITIS: RESULTS OF THE PIVOTAL PHASE 3 GLISTEN TRIAL

Cynthia Levy

Long-term outcome post-LTx in adults

Patrizia Burra

UEG Presentation

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... for medical therapy in inflammatory bowel diseases

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... for medical therapy in inflammatory bowel diseases

Chris Lamb 1

Affiliations

1 Newcastle Hospitals NHS Foundation Trust, Newcastle, United Kingdom

Summary

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Abstract

Event

UEG Week Berlin 2025

Topics

Colorectal IBD Surgery

Session

Predicting patient outcomes...

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Vanessa Stadlbauer

… after ileocecal resection of localised Crohn's disease

Matthieu Allez

LINERIXIBAT SIGNIFICANTLY IMPROVES CHOLESTATIC PRURITUS IN PRIMARY BILIARY CHOLANGITIS: RESULTS OF THE PIVOTAL PHASE 3 GLISTEN TRIAL

Cynthia Levy

Long-term outcome post-LTx in adults

Patrizia Burra

UEG Presentation

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How to handle the frail

Jonas Halfvarson 1

Affiliations

1 Örebro University, Örebro, Sweden

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Abstract

Event

UEG Week Berlin 2025

Topics

IBD Nurses Paediatrics Primary Care

Session

IBD across all ages

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Vanessa Stadlbauer

… after ileocecal resection of localised Crohn's disease

Matthieu Allez

LINERIXIBAT SIGNIFICANTLY IMPROVES CHOLESTATIC PRURITUS IN PRIMARY BILIARY CHOLANGITIS: RESULTS OF THE PIVOTAL PHASE 3 GLISTEN TRIAL

Cynthia Levy

Long-term outcome post-LTx in adults

Patrizia Burra

UEG Presentation

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MICROPLASTIC-INDUCED ALTERATIONS IN GUT MICROBIOME AND METABOLISM: INSIGHTS FROM AN EX VIVO BIOREACTOR MODEL

This content is part of Gutflix. Log in with your myUEG account, or create one free, to watch it.

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MICROPLASTIC-INDUCED ALTERATIONS IN GUT MICROBIOME AND METABOLISM: INSIGHTS FROM AN EX VIVO BIOREACTOR MODEL

Christian Pacher-Deutsch 1, Kristina Žukauskaitė 1, Cigdem Akar 2, Maximilian Nepel 2, Lukas Kogler 3, Hansjörg Habisch 2, Serena Ducoli 4, Stefania Federici 4, Tobias Madl 5, Verena Pichler 6, Angela Horvath 1, Vanessa Stadlbauer 7

Affiliations

1 Center for Biomarker Research in Medicine (CBmed), Graz, Austria|||Medical University of Graz, Graz, Austria

2 Medical University of Graz, Graz, Austria

3 Center for Biomarker Research in Medicine (CBmed), Graz, Austria|||University of Vienna, Vienna, Austria|||Medical University of Vienna, Vienna, Austria

4 University of Brescia, Brescia, Italy

5 Medical University of Graz, Graz, Austria|||BioTechMed-Graz, Graz, Austria

6 Center for Biomarker Research in Medicine (CBmed), Graz, Austria|||University of Vienna, Vienna, Austria

7 Center for Biomarker Research in Medicine (CBmed), Graz, Austria|||Medical University of Graz, Graz, Austria|||BioTechMed-Graz, Graz, Austria

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Abstract

Introduction

Microplastic particles (MPs), defined as plastic fragments smaller than 5 mm, are pervasive pollutants that accumulate in ecosystems and the human food chain (1). Literature points at various health risks, including the induction of carcinogenesis (2). Emerging evidence from animal models (3) suggests that MPs may influence the gut microbiome, but the impact on the human gut microbiome remains poorly understood.

Aims & Methods

This study aimed to evaluate how various MP types influence gut microbial composition and metabolism using an ex vivo bioreactor model, with a focus on exploring potential carcinogenic effects arising from MP–microbiome interactions.
Stool samples from healthy donors were used to inoculate bioreactor cultures, which were maintained under anaerobic conditions for five days with daily nutrient feeding. These cultures were exposed to five common MP types—polystyrene (PS), polypropylene (PP), low-density polyethylene (LDPE), poly(methyl methacrylate) (PMMA), and polyethylene terephthalate (PET)—at concentrations mimicking both estimated human exposure (4) and higher doses to assess dose-dependence. Cell viability and total bacterial counts, as well as culture pH, were measured throughout the experiment. To further explore potential microbiome and metabolic alterations, 16S rRNA gene sequencing and targeted metabolomics were performed.

Results

MP exposure did not lead to significant changes in total or viable bacterial cell counts. However, MP-treated cultures exhibited a consistent and significant decrease in pH compared to controls, suggesting changes in microbial metabolic activity. Microbiome sequencing revealed plastic-type-dependent alterations in microbial composition, with certain bacterial taxa increasing or decreasing in abundance depending on the MP type. These shifts occurred across multiple genera within diverse families, including Lachnospiraceae, Oscillospiraceae, Enterobacteriaceae, and Ruminococcaceae, with the majority of changes occurring withing the phylum Bacillota. These compositional changes were accompanied by shifts in the metabolomic profiles, some of which correlated with the observed pH changes. Several plastic types induced changes in valeric acid levels, while individual MP types were associated with alterations in distinct metabolites such as uracil, lactic acid, and acetic acid.

Conclusion

This study demonstrates that MPs can affect gut microbial activity and metabolism without significantly altering overall bacterial abundance in the short term. The variation in microbiome response across plastic types highlights the complexity of MP-microbiome interactions. Changes in faecal pH are known to be associated with various gastrointestinal diseases (5). Interestingly, some of the MP-induced changes in microbial composition resembled patterns linked to diseases such as depression and colorectal cancer. In contrast, other changes showed patterns that differed from those typically associated with conditions like Parkinson’s disease and irritable bowel syndrome, highlighting the complexity of these associations and the dependency on the context. The bioreactor model provided a controlled environment for identifying direct MP-microbiome interactions; however, in humans, additional factors like diet, immune response, and individual microbiome variations play a role in determining long-term effects. Exposure duration may also play a critical role in shaping the extent and nature of microbiome alterations (6), underscoring the need for further research into the effects of chronic MP exposure and associated health risks.

References

(1) Mamun, A. A., Prasetya, T. A. E., Dewi, I. R., & Ahmad, M. (2023). Microplastics in human food chains: Food becoming a threat to health safety. The Science of the total environment, 858(Pt 1), 159834. https://doi.org/10.1016/j.scitotenv.2022.159834
(2) Kumar, R., Manna, C., Padha, S., Verma, A., Sharma, P., Dhar, A., Ghosh, A., & Bhattacharya, P. (2022). Micro(nano)plastics pollution and human health: How plastics can induce carcinogenesis to humans?. Chemosphere, 298, 134267. https://doi.org/10.1016/j.chemosphere.2022.134267
(3) Hirt, N., & Body-Malapel, M. (2020). Immunotoxicity and intestinal effects of nano- and microplastics: a review of the literature. Particle and fibre toxicology, 17(1), 57. https://doi.org/10.1186/s12989-020-00387-7
(4) Senathirajah, K., Attwood, S., Bhagwat, G., Carbery, M., Wilson, S., & Palanisami, T. (2021). Estimation of the mass of microplastics ingested - A pivotal first step towards human health risk assessment. Journal of hazardous materials, 404(Pt B), 124004. https://doi.org/10.1016/j.jhazmat.2020.124004
(5) Yamamura, R., Inoue, K. Y., Nishino, K., & Yamasaki, S. (2023). Intestinal and fecal pH in human health. Frontiers in Microbiomes, 2, 1192316.
(6) Yin, L., Yang, M., Teng, A., Ni, C., Wang, P., & Tang, S. (2025). Unraveling Microplastic Effects on Gut Microbiota across Various Animals Using Machine Learning. ACS nano, 19(1), 369–380. https://doi.org/10.1021/acsnano.4c07885

Event

UEG Week Berlin 2025

Topics

Gut Microbiota Colorectal

Submission format

Abstract

Session

The gut ecosystem: From pathogenesis to treatment

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Chris Lamb

How to handle the frail

Jonas Halfvarson

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Vanessa Stadlbauer

… after ileocecal resection of localised Crohn's disease

Matthieu Allez

LINERIXIBAT SIGNIFICANTLY IMPROVES CHOLESTATIC PRURITUS IN PRIMARY BILIARY CHOLANGITIS: RESULTS OF THE PIVOTAL PHASE 3 GLISTEN TRIAL

Cynthia Levy

Long-term outcome post-LTx in adults

Patrizia Burra

UEG Presentation

Share via Email Share on Facebook Share on X Share on LinkedIn Share on Bluesky

… after ileocecal resection of localised Crohn's disease

This content is part of Gutflix. Log in with your myUEG account, or create one free, to watch it.

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… after ileocecal resection of localised Crohn's disease

Matthieu Allez 1

Affiliations

1 Saint-Louis Hospital, AP-HP, Université Paris Cité, Paris, France

Summary

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Abstract

Event

UEG Week Berlin 2025

Topics

Colorectal IBD Surgery

Session

Predicting patient outcomes...

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

More Like This:

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Chris Lamb

How to handle the frail

Jonas Halfvarson

MICROPLASTIC-INDUCED ALTERATIONS IN GUT MICROBIOME AND METABOLISM: INSIGHTS FROM AN EX VIVO BIOREACTOR MODEL

Vanessa Stadlbauer

… after ileocecal resection of localised Crohn's disease

Matthieu Allez

LINERIXIBAT SIGNIFICANTLY IMPROVES CHOLESTATIC PRURITUS IN PRIMARY BILIARY CHOLANGITIS: RESULTS OF THE PIVOTAL PHASE 3 GLISTEN TRIAL

Cynthia Levy

Long-term outcome post-LTx in adults

Patrizia Burra

UEG Presentation

Share via Email Share on Facebook Share on X Share on LinkedIn Share on Bluesky

LINERIXIBAT SIGNIFICANTLY IMPROVES CHOLESTATIC PRURITUS IN PRIMARY BILIARY CHOLANGITIS: RESULTS OF THE PIVOTAL PHASE 3 GLISTEN TRIAL

This content is part of Gutflix. Log in with your myUEG account, or create one free, to watch it.

Not sure what you can access? Learn more about account types.

LINERIXIBAT SIGNIFICANTLY IMPROVES CHOLESTATIC PRURITUS IN PRIMARY BILIARY CHOLANGITIS: RESULTS OF THE PIVOTAL PHASE 3 GLISTEN TRIAL

Gideon M. Hirschfield 1, Christopher L. Bowlus 2, David Jones 3, Andreas E. Kremer 4, Marlyn J. Mayo 5, Atsushi Tanaka 6, Pietro Andreone 7, Jidong Jia 8, Qinglong Jin 9, Ricardo Macias-Rodriguez 10, Alexander R. Cobitz 11, Brooke M. Currie 11, Ciara Gorey 12, Ivana Lazic 12, Danielle J. Podmore 12, Andrea Ribiero 13, Jennifer B. Shannon 14, Brandon Swift 14, Megan M. McLaughlin 11, Cynthia Levy 15

Affiliations

1 Toronto General Hospital, Toronto, Canada

2 University of California Davis School of Medicine, Sacramento, United States

3 Newcastle University, Newcastle Upon Tyne, United Kingdom

4 University Hospital Zurich, Zurich, Switzerland

5 University of Texas Southwestern Medical School, Dallas, United States

6 Teikyo University School of Medicine, Tokyo, Japan

7 Azienda Ospedaliero-Universitaria di Modena and Università di Modena e Reggio Emilia, Modena, Italy

8 Capital Medical University, Beijing, China

9 The First Hospital of Jilin University, Changchun, China

10 Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

11 GSK, Collegeville, United States

12 GSK, London, United Kingdom

13 GSK, Madrid, Spain

14 GSK, Durham, United States

15 University of Miami, Miami, United States

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Abstract

Introduction

Cholestatic pruritus is common, debilitating and undertreated in patients with primary biliary cholangitis (PBC). Here, we describe the results of GLISTEN (NCT04950127), a Phase 3 study investigating the efficacy and safety of the ileal bile acid transporter inhibitor linerixibat for pruritus in PBC.

Aims & Methods

In this double-blind, randomised, placebo-controlled study, patients with PBC and moderate-to-severe pruritus received oral linerixibat 40 mg or placebo twice daily. Pruritus severity and pruritus-related sleep interference were assessed using a 0–10 numerical rating scale. The primary endpoint was change from baseline in worst itch over 24 weeks. Secondary endpoints included: at Week 2, change in worst itch; over 24 weeks, change in sleep interference; at Week 24, proportion of responders (≥ 2-, ≥ 3-, ≥ 4-point reduction in worst itch) and analysis of responses to 2 patient global impression items (itch severity and change). Safety endpoints included adverse event (AE) reporting.

Results

238 patients were randomised; 95% were female, itch severity was mean (standard deviation [SD]) 7.34 (1.54), 52% had alkaline phosphatase < 1.67 times upper limit of normal, and 47% were receiving stable therapy for pruritus. Pruritus improvement over 24 weeks was significantly greater with linerixibat than placebo: least-squares (LS) mean change -2.86 versus -2.15, adjusted mean difference -0.72; p = 0.001. At Week 24, the observed mean (SD) difference from baseline in pruritus was -3.66 (2.50) with linerixibat and -2.82 (2.32) with placebo. The effect of linerixibat was rapid and superior to placebo at Week 2: LS mean change -1.78 versus -1.07, adjusted mean difference -0.71; p < 0.001. Linerixibat also significantly improved pruritus-related sleep interference over 24 weeks versus placebo: LS mean change ‑2.77 versus -2.24, adjusted mean difference -0.53; p = 0.024. At Week 24, more patients on linerixibat than placebo achieved a ≥ 2-point (68% vs 64%), ≥ 3-point (56% vs 43%) or ≥ 4-point (41% vs 29%) reduction in pruritus and a higher proportion of linerixibat than placebo-treated patients reported their pruritus was very much improved (55% vs 37%) or absent (21% vs 9%). AEs reported more frequently with linerixibat than placebo were predominantly gastrointestinal (GI), including diarrhoea (61% vs 18% of patients) and abdominal pain (18% vs 3% of patients); 4% of patients in the linerixibat group discontinued treatment due to diarrhoea.

Conclusion

In patients with PBC and moderate-to-severe pruritus, linerixibat rapidly and significantly improved pruritus and pruritus-related sleep interference versus placebo. While GI AEs were more common with linerixibat than placebo, they rarely led to treatment discontinuation.

Disclosure

Funded by GSK. Various authors declare conflicts of interest as consultants, employee, recipients of grants and stockholders. These will be reported in full during the presentation.

Event

UEG Week Berlin 2025

Topics

Hepatobiliary Immunology Mechanisms & Personalised Medicine

Submission format

Abstract

Session

Advances in management of immune-mediated biliary disease

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Vanessa Stadlbauer

… after ileocecal resection of localised Crohn's disease

Matthieu Allez

LINERIXIBAT SIGNIFICANTLY IMPROVES CHOLESTATIC PRURITUS IN PRIMARY BILIARY CHOLANGITIS: RESULTS OF THE PIVOTAL PHASE 3 GLISTEN TRIAL

Cynthia Levy

Long-term outcome post-LTx in adults

Patrizia Burra

UEG Presentation

Share via Email Share on Facebook Share on X Share on LinkedIn Share on Bluesky

This content is part of Gutflix. Log in with your myUEG account, or create one free, to watch it.

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Long-term outcome post-LTx in adults

Patrizia Burra 1

Affiliations

1 University of Padua-Multivisceral Transplant Unit- Gastroenterology, Padova, Italy

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Abstract

Event

UEG Week Berlin 2025

Topics

Hepatobiliary Surgery

Session

New developments in liver transplantation

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Matthieu Allez

LINERIXIBAT SIGNIFICANTLY IMPROVES CHOLESTATIC PRURITUS IN PRIMARY BILIARY CHOLANGITIS: RESULTS OF THE PIVOTAL PHASE 3 GLISTEN TRIAL

Cynthia Levy

Long-term outcome post-LTx in adults

Patrizia Burra