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C7M, A MARKER OF TYPE VII COLLAGEN DEGRADATION, IS REFLECTIVE OF EPITHELIAL REMODELING AND IS STRONGLY ASSOCIATED WITH INTESTINAL MUCOSAL DAMAGE IN CROHN’S DISEASE

Joachim Høg Mortensen 1, Anja Poulsen 2, Marta Sorokina Alexdóttir 1, Thomai Tsapanou-Katranara 1, Lene Buhl Riis 3, Pernille Dige Ovesen 4, Julie Rasmussen 5, Mads Damsgaard Wewer 6, Louise Camilla Porsbjerg 2, Ismail Gögenur 5, Johan Burisch 7, Anne-Christine Bay-Jensen 1, Jakob Seidelin 8, Morten Asser Karsdal 1

Affiliations

1 Nordic Bioscience A/S, Herlev, Denmark

2 Rigshospitalet, Copenhagen Ø, Denmark

3 Herlev Hospital, Herlev, Denmark|||Rigshospitalet, Copenhagen Ø, Denmark

4 Herlev Hospital, Herlev, Denmark

5 Køge Hospital, København S, Denmark

6 Amager Hvidovre University Hospital, Hvidovre, Denmark

7 Hvidovre University Hospital, Virum, Denmark|||University of Copenhagen, Copenhagen, Denmark

8 Rigshospitalet, University Of Copenhagen, Copenhagen, Denmark

Summary

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C7M, a biomarker of type VII collagen degradation, was elevated in fibrostenotic Crohn's disease patients compared to luminal disease patients and showed a transient spike after surgical resection that normalized within one month.

In a prospective cohort of 62 fibrostenotic and 49 luminal Crohn's disease patients, baseline serum C7M levels were significantly higher in fibrostenotic patients (median 9.79 ng/mL) than luminal patients (median 6.03 ng/mL) with p<0.01 and AUC 0.69.
C7M levels rose sharply on post-operative day 1 in resected patients (p<0.0001, AUC 0.81) and returned to baseline by one month post-surgery, resembling levels in luminal disease patients (p<0.0001, AUC 0.80).
C7M showed mild-moderate correlations with inflammatory markers including CRP (rho=0.62, p<0.0001), albumin (rho=-0.52, p<0.0001), hemoglobin (rho=-0.28, p=0.0024), and fecal calprotectin (rho=0.25, p=0.019).
The authors suggest C7M may be relevant for assessing mucosal integrity and inflammatory burden in Crohn's disease, particularly in fibrostenotic phenotypes.

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Abstract

Introduction

Epithelial injury is a hallmark of chronic mucosal damage in Crohn’s disease (CD), which can lead to fibrostenotic strictures. Type VII collagen, a critical component of the epithelial basement membrane, forms U-shaped anchoring fibrils that link the basement membrane to the interstitial matrix by binding fibrillar collagen. Genetic mutations in the COL7A1 gene, which encodes type VII collagen, are known to impair fibril formation and reduce tissue tensile strength, resulting in epithelial dysfunction, as seen in disorders such as dystrophic epidermolysis bullosa. This highlights the essential structural role of type VII collagen in maintaining matrix stability. In CD, the importance of this protein is underscored by the presence of autoantibodies targeting type VII collagen in up to 50% of patients with CD. Loss of tissue integrity, because of loss of the interaction between the basement and interstitial matrix, leads to tissue dysfunction and fibrosis.

Aims & Methods

We investigated C7M, a biomarker of type VII collagen degradation, to assess its specificity for intestinal mucosal damage. We analyzed serum samples from CD patients enrolled in a prospective cohort study. The cohort included 62 CD patients undergoing surgical resection for fibrostenotic strictures and 49 patients with luminal disease receiving treatment adjustments without surgery. Serum was collected at baseline, post-operative day 1 (POD1), and one-month post-resection. C7M levels were quantified using a competitive ELISA.

Results

At baseline, C7M levels were significantly elevated in fibrostenotic CD patients (median: 9.79ng/mL) compared to those with luminal CD patients (median: 6.03ng/mL) (p<0.01, AUC: 0.69). In the resected group, C7M levels rose sharply on POD1 (p<0.0001, AUC: 0.81), suggesting acute release in response to surgical injury. By one-month post-surgery, C7M levels had returned to baseline, closely resembling those observed in luminal CD patients (p<0.0001, AUC: 0.80). C7M also demonstrated mild-moderate correlations to biochemical markers of inflammation, including CRP (rho=0.62, p<0.0001), hemoglobin (rho=-0.28, p=0.0024), thrombocytes (rho=0.24, p=0.0105), albumin (rho=-0.52, p<0.0001), and fecal calprotectin (rho=0.25, p=0.019).

Conclusion

C7M was elevated in fibrostenotic CD patients relative to luminal CD, indicating its potential as a biomarker of more severe or complex mucosal pathology. The pronounced but transient increase following surgery, with normalization within one month, further supports C7M as a dynamic marker of intestinal epithelial damage. These findings suggest C7M may serve as a novel, disease-specific biomarker for assessing mucosal integrity and inflammatory burden in CD.

Disclosure

Full time employee at Nordic Bioscience

Conference

UEG Week Berlin 2025

Topics

IBD

Submission format

Abstract

Session

Advances in fibrosis research in Crohn's disease (Posters)

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Abstract

Event

UEG Week Berlin 2025

Session

Abstracts I: Management and education

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Requirements for clinical trials and for the authorisation of new medicines in Europe

Elmer Schabel 1

Affiliations

1 Bundesinstitut für Arzneimittel und Medizinprodukte Abt. 2/FG Gastroenterologie, Bonn, Germany

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Abstract

Event

UEG Week Berlin 2025

Topics

Mechanisms & Personalised Medicine

Session

The art of making clinical research precise: Clinical research in context

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Massimo Bellini

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Nurse Programme (Complete Session)

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Abstract

Event

UEG Week Berlin 2025

Session

IBD nurses: All around the gut

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Massimo Bellini

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Anne Vidil

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EFFECTS OF GAMMA-AMINOBUTYRIC ACID SUPPLEMENTATION ON SYMPTOMS AND QUALITY OF LIFE IN IBS-D PATIENTS. PRELIMINARY RESULTS FROM A RANDOMIZED, DOUBLE BLINDED, PLACEBO CONTROLLED, CROSSOVER STUDY

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

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EFFECTS OF GAMMA-AMINOBUTYRIC ACID SUPPLEMENTATION ON SYMPTOMS AND QUALITY OF LIFE IN IBS-D PATIENTS. PRELIMINARY RESULTS FROM A RANDOMIZED, DOUBLE BLINDED, PLACEBO CONTROLLED, CROSSOVER STUDY

Christian Lambiase 1, Lorenzo Cancelli 1, Antonio Grosso 1, Riccardo Tedeschi 1, Francesco Rettura 1, Andrea Bottari 1, Giulia Valdiserra 2, Letizia Campigli 2, Luca Antonioli 2, Matteo Fornai 2, Nicola de Bortoli 1, Massimo Bellini 1

Affiliations

1 University of Pisa, Pisa, Italy|||Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy

2 University of Pisa, Pisa, Italy

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Abstract

Introduction

Emerging evidence suggests a possible role for γ-aminobutyric acid (GABA) in the development of irritable bowel syndrome with diarrhea (IBS-D), as well as its possible therapeutic use.

Aims & Methods

This study primary aimed to assess the efficacy of a GABA-based supplement in patients with IBS-D in terms of improvement in quality of life. Secondary aims included assessing its impact on psychological wellbeing and gastrointestinal symptoms.
In this double-blind, placebo-controlled, single center, crossover pilot study, 20 IBS-D patients were randomized to receive a food supplement containing GABA and Melissa officinalis or a placebo, at the dosage of one tablet three times daily for two treatment periods of 4 weeks each, separated by a 2-week washout period. Before and after each treatment, patients were assessed through:

IBS Symptom Severity Scale (IBS-SSS). Responders were those with a ≥50-point reduction in IBS-SSS.
Short Form Health Survey 36 (SF-36) multidimensional questionnaire.
Hospital Anxiety and Depression Scale (HADS).

Pre- and post-treatment values were compared using a paired t-test; treatment comparisons used mixed models analysis.

Results

Eighteen patients completed the study (10 females, age 30.3±10.3 years).
A significant reduction of IBSS-SSS total score, as well as in all individual items, was observed in the GABA group (Table 1). A reduction of at least 50 points was achieved in 66.7% of patients treated with GABA and in 33.3% of those treated with placebo. Mixed models analysis showed a significant improvement with GABA compared to placebo in the IBS-SSS total score (p=0.01) and in the «Bowel satisfaction» item (p=0.005).
A significant improvement on the «Mental health» (p=0.007) and «Bodily pain» (p=0.09) items and in the mental composite score (MCS) of the SF-36 (0.037, Table 1) was observed with GABA. Mixed models analysis showed a significant improvement with GABA compared to placebo in the «Physical limitations» (p=0.033) and «Emotional limitation» (p=0.028) domains of SF-36.
GABA supplementation significantly improved the «HAD-Anxiety» score compared to baseline (6.7±3.0 Vs 5.1 ±2.7, p=0.02, Table 1) even though at mixed model analysis there was no significant effect.

Table 1. Comparison between pre- and post-treatment in placebo and GABA arms of the study.

	Variable	Placebo Before treatment	Placebo After treatment	p-value	GABA Before treatment	GABA After treatment	p-value
IBS-SSS	Abdominal pain	47.4±24.8	36.0±23.5	0.006	54.7±23.1	32.2±26.4	0.004
	Days with abdominal pain	48.3±27.5	42.2±31.2	0.238	50.6±29.0	33.3±28.9	0.004
	Abdominal distention	52.6±30.5	44.2±26.9	0.045	56.2±28.5	36.1±27.4	0.008
	Satisfaction with bowel habits	76.9±19.9	74.4±20.8	0.491	73.1±23.8	55.1±31.0	0.007
	Bowel interference	65.1±24.5	62.3±25.2	0.591	68.5±19.9	54.1±26.6	0.018
SF-36	Total score	290.3±98.6	259.2±100.5	0.017	303.0±93.9	210.9±114.5	<0.001
	Mental Health	59.3±15.7	67.1±10.5	0.030	60.2±15.9	68.9±16.0	0.006
	Bodily pain	58.8±20.1	61.0±18.2	0.565	58.8±17.0	69.9±20.4	0.009
	MCS	49.8±2.4	50.1±2.4	0.564	49.7±2.7	50.9±2.4	0.042

Conclusion

In this pilot study, GABA and Melissa officinalis supplementation showed a higher overall improvement in IBS-D symptoms (IBS-SSS total) and particularly in bowel habits satisfaction compared to placebo. GABA supplementation was superior to placebo in improving daily functioning, especially regarding physical and emotional limitations in IBS-D patients. GABA may be a valuable therapeutic option deserving further investigation in larger trials.

Disclosure

No conflicts of interest to declare

Event

UEG Week Berlin 2025

Topics

Colorectal

Submission format

Abstract

Session

Lower GI motility III

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Massimo Bellini

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Anne Vidil

Laudatio UEG Lifetime Achievement Awardee

Mario Dinis-Ribeiro

UEG Presentation

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

Accreditation for a newly recruited endoscopy nurse

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.

Accreditation for a newly recruited endoscopy nurse

Anne Vidil 1

Affiliations

1 None, None, France

Summary

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Abstract

Event

UEG Week Berlin 2025

Topics

Nurses

Session

Education: Important tool for quality in endoscopy

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Massimo Bellini

Accreditation for a newly recruited endoscopy nurse

Anne Vidil

Laudatio UEG Lifetime Achievement Awardee

Mario Dinis-Ribeiro

UEG Presentation

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Laudatio UEG Lifetime Achievement Awardee

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.

Laudatio UEG Lifetime Achievement Awardee

Mario Dinis-Ribeiro 1

Affiliations

1 IPO Porto, Porto, Portugal

Summary

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Abstract

Event

UEG Week Berlin 2025

Topics

Immunology

Session

Opening Plenary

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Massimo Bellini

Accreditation for a newly recruited endoscopy nurse

Anne Vidil

Laudatio UEG Lifetime Achievement Awardee

Mario Dinis-Ribeiro

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