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ENRICHMENT OF POLYSTYRENE-DEGRADING MICROBES IN THE UPPER GASTROINTESTINAL TRACT OF FUNCTIONAL DYSPEPSIA PATIENTS

Emily Hoedt 1, Jennifer Pryor 1, Ayesha Shah 2, Gerald J. Holtmann 2, Nicholas J. Talley 1, Simon Keely 1

Affiliations

1 University of Newcastle, Newcastle, Australia|||Hunter Medical Research Institute, Newcastle, Australia

2 Princess Alexandra Hospital, Brisbane, Australia|||University of Queensland, Brisbane, Australia

Summary

AI Generated

Re-analysis of duodenal microbiome data reveals differential abundance of predicted plastic-degrading genes in functional dyspepsia patients compared to controls, with some genes enriched in patients and others in controls.

Two 16S rRNA datasets were analysed (study 1: 17 FD, 11 controls; study 2: 61 FD, 38 controls) using consistent bioinformatics and PICRUSt2 functional prediction to assess plastic-degrading microbial capacity
In the first dataset, no significant differences in predicted polyethylene terephthalate utilization pathways were found in duodenal mucosa, but partial TCA cycle pathways were increased in gastric mucosa of FD patients
In the second dataset, the gene 3-oxoadipate enol-lactonase was significantly increased in FD patients, while two other polyethylene-associated degradation genes were significantly increased in controls
The authors conclude that PET-degrading microbes are significantly enriched in the upper gastrointestinal tract of FD patients and suggest these findings highlight potential microbial biomarkers warranting further investigation

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Abstract

Introduction

Microplastics are unavoidable in our current environment and can enter the human body through ingestion, inhalation, and skin contact. Gut microbes play a role in plastic degradation, breaking down polymers into smaller molecules through enzymatic processes like depolymerization and oxidation, which can then be used as a carbon source (1). However, there is mounting alarming evidence that implicates microplastics in causing oxidative stress, DNA damage, and chronic inflammation, potentially leading to various health issues, including gastrointestinal disorders (2-4). In individuals with digestive disorders such as DGBI (disorders of gut-brain interaction), microplastics may exacerbate symptoms by disrupting gut microbiome and immune responses. Previously, within a functional dyspepsia (FD) cohort we identified a strong positive correlation between plastic degrading Exiguobacterium genus (5) within the duodenal mucosa and mucosa Th2 immune cells (6).

Aims & Methods

We aimed to investigate the differential abundance of microbes and metabolic pathways known to degrade plastics in patients with FD. Previously, we have published the 16S duodenal mucosa associated microbiome sequence data for FD (n=17) and asymptomatic control (n=11) groups (6), in addition we conducted a systematic review and retrieved 1 raw duodenal mucosa-associated microbiome 16S sequence dataset (FD n=61, controls n=38) for re-analysis with a consistent bioinformatic pipeline. This included quality assessment, demultiplexing and denoising with QIIME2 and taxonomic assignment with SILVA database. Functional differences in the microbiome were predicted with PICRUSt2. Differentially abundant plastic utilising genes were assessed in R, after CLR-transformation.

Results

As the two 16S upper gastrointestinal mucosa microbiome FD studies were sequenced separately, and the batch effect are pronounced we could not combine them for pooled analysis. When we examined the first study for predicted metabolic pathways for differential polyethylene terephthalate (PET) utilization when comparing FD patients to controls in the duodenum mucosa-associated microbiome, we did not identify any significant differences. An increase in the "partial TCA cycle (obligate autotrophs)" was observed in the gastric mucosa-associated microbiome of FD patients vs controls; PET by-products have been linked to the TCA cycle (7).
The study retrieved through our systematic review identified several significantly increased predicted functional polyethylene-associated genes, primarily from later stages of degradation. The findings revealed that the gene 3-oxoadipate enol-lactonase [EC:3.1.1.24] was significantly increased in FD patients. Furthermore, the genes 5-carboxymethyl-2-hydroxymuconic-semialdehyde dehydrogenase [EC:1.2.1.60] and 5-oxopent-3-ene-1,2,5-tricarboxylate decarboxylase/2-hydroxyhepta-2,4-diene-1,7-dioate isome were significantly increased in controls. Finally, 5-carboxymethyl-2-hydroxymuconate isomerase [EC:5.3.3.10] was also increased in controls though not significantly.

Conclusion

Our recent microbiome analysis reveals a significant enrichment of PET-degrading microbes colonising the upper gastrointestinal tract of patients with FD compared to controls. These findings provide new insights into the microbial and immune landscape of FD patients, highlighting potential microbial biomarkers and immune associations that warrant further investigation.

References

1. Yang X-G, Wen P-P, Yang Y-F, Jia P-P, Li W-G, Pei D-S. 2023. Plastic biodegradation by in vitro environmental microorganisms and in vivo gut microorganisms of insects. Frontiers in Microbiology
2. Jayavel S, Govindaraju B, Michael JR, Viswanathan B. 2024. Impacts of micro and nanoplastics on human health. Bulletin of the National Research Centre
3. Cheng Y, Yang Y, Bai L, Cui J. 2024. Microplastics: an often-overlooked issue in the transition from chronic inflammation to cancer. J Transl Med
4. Han Q, Gao X, Wang S, Wei Z, Wang Y, Xu K, Chen M. 2023. Co-exposure to polystyrene microplastics and di-(2-ethylhexyl) phthalate aggravates allergic asthma through the TRPA1-p38 MAPK pathway. Toxicology Letters
5. Parthasarathy A, Miranda RR, Eddingsaas NC, Chu J, Freezman IM, Tyler AC, Hudson AO. 2022. Polystyrene Degradation by Exiguobacterium sp. RIT 594: Preliminary Evidence for a Pathway Containing an Atypical Oxygenase. Microorganisms
6. Hoedt EC, Burns GL, Kang S, Bruce J, Morrison M, Keely S, Talley NJ. 2025. Altered Duodenal Mucosa-Associated Microbiota and Immune Profiles in Functional Dyspepsia: A Study of Host-Microbiome Homeostasis. bioRxiv doi:10.1101/2025.04.10.648308:2025.04.10.648308.
7. Carr CM, Clarke DJ, Dobson ADW. 2020. Microbial Polyethylene Terephthalate Hydrolases: Current and Future Perspectives. Front Microbiology

Disclosure

Keely reports consultancy and positions held on advisory boards for: Gossamer Bio (Scientific Advisory Board), Anatara Lifescience (Scientific Advisory Board), Microba Life Science (Consultancy) and Immuron Ltd. (Consultancy).
Talley reports personal fees from Biocodex (FD) (2024), Brown University (fiber and laxation), Microba (microbiome), outside the submitted work. NJT has a patent Licensing Questionnaires Talley Bowel Disease Questionnaire licensed to Mayo/Talley and Nepean Dyspepsia Index (NDI) 1998, patent “Diagnostic marker for functional gastrointestinal disorders” Australian Provisional Patent Application 2021901692, “Methods and compositions for treating age-related neurodegenerative disease associated with dysbiosis” US Application No. 63/537,725.

Conference

UEG Week Berlin 2025

Topics

Oesophagus

Submission format

Abstract

Session

Dyspepsia (Posters)

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

More Like This:

VISIBLE ABDOMINAL DISTENSION AND BLOATING SENSATION: RESPONSES TO A NON-INSTRUMENTAL BIOFEEDBACK TREATMENT.

Fernando Azpiroz

TOWARDS A NATIONAL SCREENING PROGRAM FOR COELIAC DISEASE AND TYPE 1 DIABETES: AN ITALIAN FEASIBILITY PILOT PROJECT (D1CE SCREEN)

Flavia Pricci

IMPACT OF DIAPHRAGMATIC RELAXING INCISION ON RECURRENCE RATE AFTER PARAESOPHAGEAL HERNIA REPAIR; 1 YEAR RESULTS OF A DOUBLE-BLIND, RANDOMIZED CLINICAL TRIAL

Marcus Reuterwall Hansson

GP: First line diagnosis and treatment

Juan Mendive

NOVEL ARTIFICIAL INTELLIGENCE-DRIVEN DETECTION LOCALISATION AND QUANTIFICATION OF NEUTROPHILS TO ASSESS DISEASE ACTIVITY AND EARLY RESPONSE TO THERAPY IN ULCERATIVE COLITIS CLINICAL TRIAL

Enrico Grisan

ACIDIC MAMMALIAN CHITINASE DEFICIENCY RESULTS IN CHIEF CELLS PYROPTOSIS AND GASTRIC REGIONAL IMMUNITY REMODELING IS THE NEW CELLULAR ORIGIN OF SPEM

Xuemei Liu

UEG Presentation

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VISIBLE ABDOMINAL DISTENSION AND BLOATING SENSATION: RESPONSES TO A NON-INSTRUMENTAL BIOFEEDBACK TREATMENT.

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VISIBLE ABDOMINAL DISTENSION AND BLOATING SENSATION: RESPONSES TO A NON-INSTRUMENTAL BIOFEEDBACK TREATMENT.

Claudia Barber 1, Teodora Pribic 2, Jordi Serra 1, Fernando Azpiroz 2

Affiliations

1 University Hospital Vall d'Hebron, Barcelona, Spain

2 Vall D'Hebron Research Institute, Barcelona, Spain

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Abstract

Introduction

In patients with disorders of the gut-brain interaction abdominal bloating is a visceral sensation (sensation of pressure/fullness), whereas visible abdominal distension is a somatic manifestation with abnormal postural tone (abdominophrenic dyssynergia, i.e., diaphragmatic push and abdominal wall relaxation). Abdominophrenic dyssynergia can be corrected by a simple non-instrumental technique, and our aim was to determine the relation of distension and bloating responses over time.

Aims & Methods

In a randomized, placebo-controlled, parallel trial (ClincalTrials.gov number NCT06150638) 40 consecutive patients (34 women, 6 men; age range 18–58 years) with disorders of gut-brain interaction complaining of visible abdominal distension were randomized to receive biofeedback or placebo. Patients in the biofeedback group were explained the mechanism of distension, and were taught to relax the diaphragm and contract the abdominal wall, using an original audiovisual support and hands-on guidance by a trained operator. In the placebo group, sham measurements of abdominal and thoracic motion were performed, and a pill of placebo was administered. Three 30-min sessions were performed over a 4-week intervention period, with instructions to perform daily exercises (biofeedback group) or to take placebo three times a day (control group) at home. After the intervention, patients allocated to the placebo group were offered biofeedback treatment. After receiving biofeedback treatment, patients in both groups were instructed to continue practicing these same exercises over time, and were followed up: visible abdominal distension and sensation of abdominal pressure/fullness (bloating) were measured at 1 and 3 months using 10-cm scales for 7 consecutive days, and the mean values (±SE) were calculated.

Results

After undergoing the three treatment sessions, abdominal distension improved in the biofeedback group (n=19; by 24±7 %), but not in the placebo group (n=20; 8±3 % change; p=0.025 vs feedback group). In the 20 patients randomized to placebo, subsequent biofeedback treatment improved abdominal distension (by 35±7 %). Follow-up in all patients after biofeedback (n=36) showed a sustained improvement in abdominal distension and bloating sensation at 1 month (by 39±5 % and 36±7 %, respectively; p<0.001 vs before treatment for both), and at 3 months (by 37±5 % and 34±8 %, respectively; p<0.003 vs before treatment for both).

Conclusion

In patients with disorders of gut-brain interaction, correction of abdominophrenic dyssynergia by a simple, non-instrumental technique, produces a sustained improvement of visible abdominal distension, associated with a concomitant improvement of bloating sensation.

Disclosure

I have the following Conflict of Interest to declare: Coloplast, Schwabe

Event

UEG Week Berlin 2025

Topics

Neurogastroenterology & Motility Oesophagus

Submission format

Abstract

Session

Lower GI motility I

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

More Like This:

VISIBLE ABDOMINAL DISTENSION AND BLOATING SENSATION: RESPONSES TO A NON-INSTRUMENTAL BIOFEEDBACK TREATMENT.

Fernando Azpiroz

TOWARDS A NATIONAL SCREENING PROGRAM FOR COELIAC DISEASE AND TYPE 1 DIABETES: AN ITALIAN FEASIBILITY PILOT PROJECT (D1CE SCREEN)

Flavia Pricci

IMPACT OF DIAPHRAGMATIC RELAXING INCISION ON RECURRENCE RATE AFTER PARAESOPHAGEAL HERNIA REPAIR; 1 YEAR RESULTS OF A DOUBLE-BLIND, RANDOMIZED CLINICAL TRIAL

Marcus Reuterwall Hansson

GP: First line diagnosis and treatment

Juan Mendive

NOVEL ARTIFICIAL INTELLIGENCE-DRIVEN DETECTION LOCALISATION AND QUANTIFICATION OF NEUTROPHILS TO ASSESS DISEASE ACTIVITY AND EARLY RESPONSE TO THERAPY IN ULCERATIVE COLITIS CLINICAL TRIAL

Enrico Grisan

ACIDIC MAMMALIAN CHITINASE DEFICIENCY RESULTS IN CHIEF CELLS PYROPTOSIS AND GASTRIC REGIONAL IMMUNITY REMODELING IS THE NEW CELLULAR ORIGIN OF SPEM

Xuemei Liu

UEG Presentation

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TOWARDS A NATIONAL SCREENING PROGRAM FOR COELIAC DISEASE AND TYPE 1 DIABETES: AN ITALIAN FEASIBILITY PILOT PROJECT (D1CE SCREEN)

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TOWARDS A NATIONAL SCREENING PROGRAM FOR COELIAC DISEASE AND TYPE 1 DIABETES: AN ITALIAN FEASIBILITY PILOT PROJECT (D1CE SCREEN)

Olimpia Vincentini 1, Chiara Porfilio 1, Adalgisa Ilaria Sedile 1, Francesca Iacoponi 1, Marika Villa 1, Emanuele Bosi 2, Valentino Cherubini 3, Antonio D'Avino 4, Marco Silano 1, Umberto Agrimi 1, Carlo Catassi 5, Vito Lampasona 2, Flavia Pricci 1

Affiliations

1 Istituto Superiore di Sanità, Rome, Italy

2 IRCCS San Raffaele Hospital, Milan, Italy

3 Azienda Ospedaliero-Universitaria, Ospedali Riuniti di Ancona, G. Salesi Hospital, Ancona, Italy

4 Federazione Italiana Medici Pediatri (FIMP), Naples, Italy

5 Polytechnic University of Marche, Ancona, Italy

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Abstract

Introduction

Celiac disease (CD) is an autoimmune disorder triggered by gluten ingestion in genetically predisposed individuals, leading to chronic intestinal inflammation. It affects about 1% of the global population and is often undiagnosed in childhood due to the absence of symptoms, with around 65% of cases in Italy going unnoticed. Early screening is a key tool for timely diagnosis and preventing long-term complications. In this perspective, the D1Ce Screen pilot study follows Italian Republic Law 130/2023, which mandates screening for pre-symptomatic CD and type 1 diabetes (T1D) in the general paediatric population through autoantibody measurements in capillary blood. Paediatric screening is a key tool for early detection and the prevention of long-term complications, associated with late or missed diagnosis. Individuals who tested positive for CD and T1D -specific autoantibodies will undergo further clinical evaluation at the regional specialized center to confirm the diagnosis

Aims & Methods

Primary objective of D1Ce Screen study is to assess, feasibility, acceptability and sustainability of a nationwide screening program, for the evaluation of undiagnosed CD cases and presymptomatic T1D. To assess operational aspects D1Ce Screen evaluates the involvement of primary care pediatricians (PCPs), blood sample collection accuracy and acceptability for families measuring anxiety, depression and quality of life through 3 validated questionnaires.
This is an observational multicenter study to screen 5,363 children in four Italian regions (Lombardy, Marche, Campania, Sardinia), distributed into three classes of age (2-2.9, 6-6.9, and 10-10.9 years), corresponding to peaks of seroconversion for these diseases. For eligibility, the inclusion criterion is age. T1D is the exclusion criterion. Voluntary PCPs were responsible for recruitment of participants, administration of informed consents and questionnaires, execution of blood drawing by finger prick, capillary blood collection and sample shipment. Specific T1D and CD autoantibodies are measured by ELISA in capillary samples. In addition, HLA DQ2 and DQ8 HLA typing is performed on dried blood spot (DBS).

Results

PCPs initially accepting to participate were 565, with 428 (75,7%) completing the study. Enrolled children were 5534, with 91,1% within the target age. The gender distribution was 49.4% females, 50.6% males. Samples suitable for analysis (adequacy for at least one assay) were 89% of the total collected. Most of DBS samples were suitable for HLA typing. The target of families undergoing questionnaire evaluation of 2% has been exceeded.

Regions	Age (yr)
	2+1	6+1	10+1	Out of range	In range	Total	Planned	%Planned
Campania	468	536	498	224	1502	1726	1739	86,37
Lombardy	824	936	1050	186	2810	2996	2867	98,01
Marche	113	123	127	19	363	382	394	92,13
Sardinia	96	126	147	61	369	430	363	101,65
Total	1501	1721	1822	490	5044	5534	5363

Conclusion

The D1Ce Screen pilot study provides evidence supporting the feasibility of a nationwide screening initiative. The active collaboration of PCPs, the high level of participation from families, and the efficient implementation of capillary blood sampling procedures were key contributors to its success. These findings confirm the potential for scalability of a paediatric screening program for T1D and CD within the framework of the Italian National Health Service. Early detection and timely initiation of a gluten-free diet in children diagnosed with CD are essential to preventing long-term complications and improving health outcomes.

References

Bosi E, Catassi C. Screening type 1 diabetes and celiac disease by law. Lancet Diabetes Endocrinol. 2024 Jan;12(1):12-14. doi: 10.1016/S2213-8587(23)00354-6

Event

UEG Week Berlin 2025

Topics

Mechanisms & Personalised Medicine Small Intestine & Nutrition

Submission format

Abstract

Session

Coeliac disease: From screening to new drugs

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

More Like This:

VISIBLE ABDOMINAL DISTENSION AND BLOATING SENSATION: RESPONSES TO A NON-INSTRUMENTAL BIOFEEDBACK TREATMENT.

Fernando Azpiroz

TOWARDS A NATIONAL SCREENING PROGRAM FOR COELIAC DISEASE AND TYPE 1 DIABETES: AN ITALIAN FEASIBILITY PILOT PROJECT (D1CE SCREEN)

Flavia Pricci

IMPACT OF DIAPHRAGMATIC RELAXING INCISION ON RECURRENCE RATE AFTER PARAESOPHAGEAL HERNIA REPAIR; 1 YEAR RESULTS OF A DOUBLE-BLIND, RANDOMIZED CLINICAL TRIAL

Marcus Reuterwall Hansson

GP: First line diagnosis and treatment

Juan Mendive

NOVEL ARTIFICIAL INTELLIGENCE-DRIVEN DETECTION LOCALISATION AND QUANTIFICATION OF NEUTROPHILS TO ASSESS DISEASE ACTIVITY AND EARLY RESPONSE TO THERAPY IN ULCERATIVE COLITIS CLINICAL TRIAL

Enrico Grisan

ACIDIC MAMMALIAN CHITINASE DEFICIENCY RESULTS IN CHIEF CELLS PYROPTOSIS AND GASTRIC REGIONAL IMMUNITY REMODELING IS THE NEW CELLULAR ORIGIN OF SPEM

Xuemei Liu

UEG Presentation

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

IMPACT OF DIAPHRAGMATIC RELAXING INCISION ON RECURRENCE RATE AFTER PARAESOPHAGEAL HERNIA REPAIR; 1 YEAR RESULTS OF A DOUBLE-BLIND, RANDOMIZED CLINICAL TRIAL

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

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IMPACT OF DIAPHRAGMATIC RELAXING INCISION ON RECURRENCE RATE AFTER PARAESOPHAGEAL HERNIA REPAIR; 1 YEAR RESULTS OF A DOUBLE-BLIND, RANDOMIZED CLINICAL TRIAL

Alexandros Tsoposidis 1, Srdjan Kostic 1, Lars Lundell 2, Ville Wallenius 1, Hans Axelsson 1, Anders Thorell 3, Bengt Håkanson 3, Marcus Reuterwall Hansson 3

Affiliations

1 University of Gothenburg, Gothenburg, Sweden

2 Karolinska Institutet, Stockholm, Sweden

3 Karolinska Institutet, Stockholm, Sweden|||Ersta Hospital, Stockholm, Sweden

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Abstract

Introduction

The optimal surgical approach to reduce recurrence rates after laparoscopic repair of paraesophageal hernia (PEH) is yet to be defined. The crural repair is challenged by both axial and transverse-lateral tension, which may compromise durability. The aim of this double-blind randomized clinical trial was to investigate whether a left-sided diaphragmatic relaxing incision in addition to standard crural repair and fundoplication reduces anatomical recurrence rates at one year postoperatively.

Aims & Methods

This study was conducted at two high-volume Swedish centers—Ersta Hospital (Stockholm) and Sahlgrenska University Hospital (Gothenburg)—between August 2019 and August 2023. Adult patients undergoing surgery for PEH were randomized 1:1 to either standard crural repair with total (360°) fundoplication (control) or the same procedure with the addition of a left-sided diaphragmatic relaxing incision covered by synthetic mesh (intervention). Patients with prior hiatal surgery, ASA class IV or above, type I hernia, major esophageal motility disorders, or any contraindication to fundoplication were excluded. Blinding for patients and assessors was maintained throughout follow-up. Pre- and postoperative assessments included computed tomography (CT), symptom questionnaires (Dakkak dysphagia score, Gastrointestinal Symptom Rating Scale [GSRS]), and quality of life (QoL, RAND-36). The primary outcome was radiologically confirmed PEH recurrence at 12 months.

Results

Of 103 patients screened, 76 were randomized (38 per group). Baseline characteristics were well balanced. CT was completed in 72 patients (95%) at 12 months. The recurrence rate was 66% in the control group and 54% in the intervention group (p=0.313). Three patients in the intervention group had asymptomatic CT verified herniation at the site of the diaphragmatic incision. There were no differences in recurrence size distribution (<4 cm vs >4 cm) between groups. Postoperative symptom assessment revealed significant improvements in dysphagia, reflux, indigestion, and abdominal pain in both groups, without intergroup differences. Physical QoL (PCS) improved significantlywhereas mental QoL (MCS) remained unchanged. Two deaths occurred within 90 days postoperatively (1 per group), yielding a 90-day mortality of 2.6%. Other complications included mediastinal abscess (n=1, intervention group) and need for postoperative endoscopic dilatation (n=5 in total). Operation time tended to be longer in the intervention group (150 vs 133 min; p=ns).

	Crural repair alone	Crural repair with relaxing diaphragmatic incision	P value
Completed CT chest at 1 year	35/38	37/38
Radiological recurrence	23 (66%)	20 (54%)	.313
Recurrence<4cm	12 (34%)	11 (30%)	.522
Recurrence>4cm	11 (31%)	9 (24%)	.457

Table 1: Radiological recurrences 1 year after surgical repair of PEH

Conclusion

In this randomized, double-blind trial, the addition of a left-sided diaphragmatic relaxing incision to standard laparoscopic PEH repair did not improve anatomical recurrence rates, symptom relief or QoL at 12 months after surgery and should not be recommended for routine use. Alternative strategies to improve recurrence rates after PEH need to be explored in the future.

Event

UEG Week Berlin 2025

Topics

Neurogastroenterology & Motility Oesophagus

Submission format

Abstract

Session

Burning issues in GERD

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

More Like This:

VISIBLE ABDOMINAL DISTENSION AND BLOATING SENSATION: RESPONSES TO A NON-INSTRUMENTAL BIOFEEDBACK TREATMENT.

Fernando Azpiroz

TOWARDS A NATIONAL SCREENING PROGRAM FOR COELIAC DISEASE AND TYPE 1 DIABETES: AN ITALIAN FEASIBILITY PILOT PROJECT (D1CE SCREEN)

Flavia Pricci

IMPACT OF DIAPHRAGMATIC RELAXING INCISION ON RECURRENCE RATE AFTER PARAESOPHAGEAL HERNIA REPAIR; 1 YEAR RESULTS OF A DOUBLE-BLIND, RANDOMIZED CLINICAL TRIAL

Marcus Reuterwall Hansson

GP: First line diagnosis and treatment

Juan Mendive

NOVEL ARTIFICIAL INTELLIGENCE-DRIVEN DETECTION LOCALISATION AND QUANTIFICATION OF NEUTROPHILS TO ASSESS DISEASE ACTIVITY AND EARLY RESPONSE TO THERAPY IN ULCERATIVE COLITIS CLINICAL TRIAL

Enrico Grisan

ACIDIC MAMMALIAN CHITINASE DEFICIENCY RESULTS IN CHIEF CELLS PYROPTOSIS AND GASTRIC REGIONAL IMMUNITY REMODELING IS THE NEW CELLULAR ORIGIN OF SPEM

Xuemei Liu

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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GP: First line diagnosis and treatment

Juan Mendive 1

Affiliations

1 European Society for Primary Care Gastroenterology (ESPCG), Sant Adrià de Besòs ( Barcelona), Spain

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Abstract

Event

UEG Week Berlin 2025

Topics

Neurogastroenterology & Motility Primary Care

Session

Therapy update: Dyspepsia

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

More Like This:

VISIBLE ABDOMINAL DISTENSION AND BLOATING SENSATION: RESPONSES TO A NON-INSTRUMENTAL BIOFEEDBACK TREATMENT.

Fernando Azpiroz

TOWARDS A NATIONAL SCREENING PROGRAM FOR COELIAC DISEASE AND TYPE 1 DIABETES: AN ITALIAN FEASIBILITY PILOT PROJECT (D1CE SCREEN)

Flavia Pricci

IMPACT OF DIAPHRAGMATIC RELAXING INCISION ON RECURRENCE RATE AFTER PARAESOPHAGEAL HERNIA REPAIR; 1 YEAR RESULTS OF A DOUBLE-BLIND, RANDOMIZED CLINICAL TRIAL

Marcus Reuterwall Hansson

GP: First line diagnosis and treatment

Juan Mendive

NOVEL ARTIFICIAL INTELLIGENCE-DRIVEN DETECTION LOCALISATION AND QUANTIFICATION OF NEUTROPHILS TO ASSESS DISEASE ACTIVITY AND EARLY RESPONSE TO THERAPY IN ULCERATIVE COLITIS CLINICAL TRIAL

Enrico Grisan

ACIDIC MAMMALIAN CHITINASE DEFICIENCY RESULTS IN CHIEF CELLS PYROPTOSIS AND GASTRIC REGIONAL IMMUNITY REMODELING IS THE NEW CELLULAR ORIGIN OF SPEM

Xuemei Liu

UEG Presentation

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

NOVEL ARTIFICIAL INTELLIGENCE-DRIVEN DETECTION LOCALISATION AND QUANTIFICATION OF NEUTROPHILS TO ASSESS DISEASE ACTIVITY AND EARLY RESPONSE TO THERAPY IN ULCERATIVE COLITIS CLINICAL 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.

NOVEL ARTIFICIAL INTELLIGENCE-DRIVEN DETECTION LOCALISATION AND QUANTIFICATION OF NEUTROPHILS TO ASSESS DISEASE ACTIVITY AND EARLY RESPONSE TO THERAPY IN ULCERATIVE COLITIS CLINICAL TRIAL

Marietta Iacucci 1, Irene Zammarchi 1, Valentina Vadori 2, Pablo Meseguer 3, Giovanni Santacroce 1, Rocio Del Amor 4, Davide Zardo 5, Brian Hayes 6, Rory Crotty 7, Louise Burke 6, Bisi Bode Kolawole 2, Ujwala Chaudhari 2, Charles Owen 8, Klaus Gottlieb 8, William J. Eastman 8, Silvio Danese 9, Subrata Ghosh 1, Valery Naranjo 4, Enrico Grisan 2

Affiliations

1 University College Cork, Cork, Ireland

2 London South Bank University, London, United Kingdom

3 Universitat Politècnica de València, Valencia, Spain|||valgrAI – Valencian Graduate School and Research Network of Artificial Intelligence, Valencia, Spain

4 Universitat Politècnica de València, Valencia, Spain|||Artikode Intelligence S.L, Valencia, Spain

5 San Bortolo Hospital, Vicenza, Italy

6 Cork University Hospital, Cork, Ireland|||University College Cork, Cork, Ireland

7 Cork University Hospital, Cork, Ireland

8 Eli Lilly And Company, Indianapolis, United States

9 Vita-Salute San Raffaele University - IRCCS San Raffaele Scientific Institute, Milan, Italy

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Abstract

Introduction

The achievement of histological remission (HR) is a key treatment goal in ulcerative colitis (UC), as it is suggestive of better disease management and predicts response to therapy.
The absence of neutrophils in epithelium and lamina is crucial to define HR. However, the role of neutrophil number and localisation remains unclear. We aimed to develop a novel artificial intelligence (AI)-driven system to automate neutrophil detection, localisation, and quantification, supporting assessment of HR and enable the prediction of response to therapy.

Aims & Methods

We developed an AI-driven system by integrating two deep learning models to (1) segment whole slide images (WSIs) into epithelium, crypts and lamina propria and to (2) detect and quantify neutrophils. Outputs from these models were combined to compute neutrophil densities in the lamina propria, epithelium, and overall tissue. The optimal neutrophil density cut-offs to assess disease activity (Geboes score >2B.0) in UC patients were identified in the AMAC phase 2 Mirikizumab trial, and subsequently validated in the multicentre prospective PICaSSO cohort study. Cut-offs to determine treatment response at weeks 12 and 52 (histological improvement [HI; Geboes score ≤3.1] and histological remission [HR; Geboes score ≤2B.0]), were also evaluated.

Results

Table 1 shows the system diagnostic performance in assessing disease activity and predicting response to therapy at W12 and W52 in the Mirikizumab cohort.
303 WSIs from active UC patients from the multicentre, randomised, double-blind, parallel-arm, placebo-controlled phase 2 clinical trial of Mirikizumab were analysed. The model yielded a DICE SØrensen of 0.57 for segmentation, precision of 82.3% and recall of 77.0% for neutrophil detection. The system identified an overall optimal neutrophil density cut-off (cells/mm²) predictive of disease activity of >21.7.0 (>10.1 and >30.4 for epithelium and lamina propria, respectively), with an accuracy of 86% (85% and 85%, respectively). Further validation in the multicenter PICaSSO cohort yielded to similar results.
Moreover, the overall optimal cut-off to predict histological remission at W52 was <20.8 (<10.4 and <27.9 for epithelium and lamina propria, respectively), with an accuracy of 82.0% (81% and 80%, respectively).

Conclusion

Our novel AI-based system demonstrates strong potential as an automated tool to detect, localise, and quantify neutrophils to assess histological activity and predict response to therapy in a clinical trial UC cohort and real-world settings. This framework could be applied in clinical trials and routine clinical practice, offering objective guidance for personalised management in UC patients.

Neutrophil localisation	Cut-off (cells/mm2)		Sensitivity (%)		Specificity (%)		Accuracy (%)
Assessment of disease activity
Epithelium	10.1		90 (83-96)		75 (56-94)		85 (78-91)
Lamina propria	30.4		93 (87-98)		72 (55-90)		85 (79-91)
Total	21.7		94 (88-99)		74 (54-89)		86 (79-92)
Prediction of response to therapy - Histological Remission
	W12	W52	W12	W52	W12	W52	W12	W52
Epithelium	10.9	10.4	73 (41-94)	75 (52-95)	82 (67-95)	90 (77-100)	78 (64-90)	81 (67-94)
Lamina propria	33	27.9	72 (41-95)	74 (50-95)	84 (67-96)	89 (71-100)	78 (65-89)	80 (67-91)
Total	26.8	20.8	74 (47-95)	74 (48-94)	84 (70-96)	93 (80-100)	79 (66-91)	82 (68-94)

References

[1] Santacroce G, Meseguer P, Zammarchi I, et al. P406 A novel active learning-based digital pathology protocol annotation for histologic assessment in Ulcerative Colitis using PICaSSO Histologic Remission Index (PHRI). Journal of Crohn's and Colitis, Volume 18, Issue Supplement_1, January 2024, Pages i843–i844
[2] Graham S, Vu QD, Jahanifar M, et al. CoNIC Challenge: Pushing the frontiers of nuclear detection, segmentation, classification and counting. Med Image Anal. 2024;92:103047.

Disclosure

MI received research grants and consultant fees from Olympus, Pentax, Eli Lilly, and Janssen. All other authors declare no competing interests.

Event

UEG Week Berlin 2025

Topics

IBD Mechanisms & Personalised Medicine

Submission format

Abstract

Session

Predicting response to IBD therapy

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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ACIDIC MAMMALIAN CHITINASE DEFICIENCY RESULTS IN CHIEF CELLS PYROPTOSIS AND GASTRIC REGIONAL IMMUNITY REMODELING IS THE NEW CELLULAR ORIGIN OF SPEM

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ACIDIC MAMMALIAN CHITINASE DEFICIENCY RESULTS IN CHIEF CELLS PYROPTOSIS AND GASTRIC REGIONAL IMMUNITY REMODELING IS THE NEW CELLULAR ORIGIN OF SPEM

Shuhui Liu 1, Zhiyuan Ma 1, Bei Ji 1, SHUN YAO 1, Taolang Li 1, Biguang Tuo 1, Xuemei Liu 1

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1 Affiliated Hospital of Zunyi Medical University, Zunyi, China

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Abstract

Introduction

Spasmolytic polypeptide expressing metaplasia (SPEM) is a cell repair lineage and is a very important phenotype of gastric mucosal injury and precancerous lesion.
Previously, parietal cells loss is considered as the first step and followed with chief cells transdiffernation to induce SPEM. But whether chief cells initial loss cause SPEM
needs to be further investigation. Acidic mammalian chitinase (CHIA) belongs to the 18 glycosidase family and is highly expressed in the chief cells. Our previous study showed that CHIA deficiency in the chief cells is the key event to induce SPME to progress to gastric cancer (Liu et al., DDW 2023 and 2024). However, the molecular role of CHIA in the development of SPEM is need further investigated.

Aims & Methods

Electron microscopy, qRT-PCR and single-cell sequencing (scRNA-seq) technology, as well as histopathological and immunofluorescence (IF) stainning with specific markers were performed in chief cells specific CHIA knockout mouse model (CHIA^rox/rox-GIF-Dre) and wild-type mice(CHIA^rox/rox), and in CHIA over - expression mice (CHIA ^rox/rox - GIF - Dre + rAAv - CHIA) and the control group (CHIA ^rox/rox - GIF - Dre + rAAv - control).

Results

Compared with CHIA^rox/rox mice, histological analysis and scRNA-seq technology data showed that loss of chief cells with increased M2 macrophage infiltration and final SPEM formation, but remaining of parietal cells in CHIA^rox/rox-GIF-Dre mice. Electron microscopy showed CHIA deficiency in mice resulted in endoplasmic reticulum was dilated and swollen, as well as the mitochondrial membrane was discontinuous of chief cells, followed with the accumulation of endoplasmic reticulum stress marker, including PERK, XBP-1, eIF2α/P-eIF2α, and GRP78, together with upregulation of pyroptosis-related marker, including NLRP3, ACS, GSDMD, NEK7, Caspase1, Caspase11, IL-1β, and IL-18, which was detected by qRT-PCR. These data indicating that target CHIA deletion caused chief cells pyroptosis. Furthermore, qRT-PCR analysis showed that CHIA deficiency caused the activation of IL33/IL-13 circuit in the mucosa of mice. Moreover, double immunofluorescence staining confirmed that upregulation and colocalization of IL-33 induced M2 macrophage polarization markers, including F4/80 and CD163⁺ with NLRP3 in the base of gastric mucosal of CHIA^rox/rox-GIF-Dre mice when compared with CHIA^rox/rox mice.Notably, CHIA^rox/rox - GIF - Dre + rAvv - CHIA mice reversed the above process compared with controls.

Conclusion

Chief cells specific CHIA deficiency resulted in endoplasmic reticulum stress mediate NLRP3 inflammasome activation to induce chief cells proptosis.
Chief cells initial loss is sufficient and the key step to activate IL-33/ST2-M2 macrophage polarization axis to induce SPEM, which is independent of parietal cells loss.

Event

UEG Week Berlin 2025

Topics

Immunology Neurogastroenterology & Motility Small Intestine & Nutrition Oesophagus Stomach & H. Pylori

Submission format

Abstract

Session

Complexity and diversity in upper GI

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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