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Introduction

It is well established that the gut microbiota plays an important role in host health and is perturbed by several factors including antibiotics and diseases like coronavirus disease 2019 (COVID-19). The microbiome contributes to the pathogenesis of ulcerative colitis (UC). Some vitamins have been shown to beneficially modulate the gut microbiome by increasing the abundance of presumed commensals. Also, probiotics could shape the intestinal microbiota leading to potential control of multiple bowel diseases and promotion of overall wellness.

Aims & Methods

In 6-month time (June 2021 to December 2021) 49 ulcerative colitis (UC) outpatients from Riga East Clinical University Hospital were included in a Cross-sectional study. All patients were divided into groups according to medically proven data about COVID-19 status (COVID-19pos vs. COVID-19neg) within the last 6 months. Information about vitamin, probiotic, and antibiotic intake, as well as fecal samples was collected. For taxonomical classifying of the gut microbiome metagenome data, MetaPhlAn v.2.6.0 tool was used. In further analysis gut microbiome (mostly bacteria phyla) and related data were analyzed with SPSS 20.0.

Results

Out of 49 patients, 31(63%) were male and 18(37%) were female, mean age was Md=38[IQR:34-51]. Fourteen patients (28.6%) have been COVID-19pos, 35(71.4%) COVID-19neg. Patients who were not using antibiotics in the last month had more Firmicutes Md= 64 [IQR:52.3-69.4] than users Md=31 [IQR:25.5-39.8], p=0.008. Only 9 patients (18.4%) consumed probiotics within the last month and 40 (81.6%) did not. Evaluating differences in bacteria composition in phylum level in-between probiotic users and non-users there were found no statistically significant difference. Most common used vitamins were vitamin D 18(64.3%), from those 15(42.9%) were COVID-19neg, 3(21.4%) COVID-19pos; vitamin C 7(32.8%), from those 4(11.4%) were COVID-19neg, 3(21.4%) COVID-19pos, p>0.5. Evaluating vitamin D and C users and non-users and bacteria type there were found no statistically significant differences.

Conclusion

Patients who were not using antibiotics in the last month had more Firmicutes than users. There were no statistically significant differences between probiotic users and non-users, nor between vitamin users and non-users.

IMPACT OF VITAMINS, PROBIOTICS, ANTIBIOTICS, AND THE HISTORY OF COVID-19 INFECTION ON THE GUT MICROBIOME IN ULCERATIVE COLITIS PATIENTS

Zane Straume 1, Nikola Krumina 2, Maija Rozenberga 3, Ilze Elbere 3, Dace Rudzite 4, Janis Pjalkovskis 3, Juliana Ozolina 1, Kaspars Megnis 3, Vita Skuja 2, Angelika Krumina 2

1 Riga East Clinical Univeristy Hospital, Riga, Latvia|||Riga Stradins University, Riga, Latvia

2 Riga Stradins University, Riga, Latvia

3 Latvian Biomedical Research and Study Centre, Riga, Latvia

4 Riga East Clinical Univeristy Hospital, Riga, Latvia

Conference

UEG Week Copenhagen 2023

Topics

IBD

Submission format

Abstract

Session

PP 05 IBD (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

UEG Standards and Guidelines

Consensus

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ABSTRACT

Background and Aim

Direct cholangioscopy and pancreatoscopy have become widely implemented techniques in the diagnostic and therapeutic algorithms of several pancreaticobiliary disorders. This study aimed to generate general and indication-specific European consensus recommendations on cholangioscopy and pancreatoscopy.

Methods

Supported by the available literature, statements were formulated and grouped into the following categories: (1) pre-procedural considerations, (2) general technical aspects, (3) biliopancreatic stones, (4) biliary strictures, and (5) other indications. The evidence level of each statement was determined using the GRADE methodology. Cholangioscopy experts were invited to participate in a modified Delphi process. When 80% consensus was not reached, the statement was modified based on expert feedback and subjected to an additional Delphi round. Statements were rejected if they failed to reach consensus after three Delphi rounds.

Results

Thirty cholangioscopy experts completed the Delphi process. Forty-two (97.6%) generated statements were accepted, of which 39 (92.9%) in the first Delphi round. 12 statements on preprocedural and periprocedural settings, 8 statements on biliopancreatic stones, 13 statements on biliary strictures, and 9 statements on other indications were accepted.

Conclusion

Using a modified Delphi process, we developed general and indication-specific consensus recommendations for cholangioscopy to guide clinical practice.

European Consensus Recommendations for Direct Cholangioscopy and Pancreatoscopy Using a Modified Delphi Process

Enrico Palmeri, Sebastian Stefanovic

Guideline

Consensus

Topics

Endoscopy Pancreas

Citation

United European Gastroenterology Journal, 2025; 13:1652–1667

Published

2025

UEG Podcast Episode

UEG Podcast

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Gut brain axis

Jutta Keller 1

1 Israelitic Krankenhaus, Hamburg, Germany

Topics

Neurogastroenterology & Motility

Published

2024

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Introduction

Biomarkers associated with the progression from gastric intestinal metaplasia (GIM) to gastric adenocarcinoma (GA) could provide valuable insights into identifying patients with increased risk for GA. Currently, the discovery of effective GA biomarkers poses a challenge due to the complexity of predictive and actionable value. Rarely can tumorigenesis be attributed solely to an individual molecule, as GA arises from the complex interplay of various intrinsic and environmental factors and collective interactions among multiple molecules.

Aims & Methods

The aim of this study was to identify potential biomarkers for the GIM-to-GA progression and potential drug repurposing for GIM. Sixty-four surgical biopsies were collected from 16 patients (4 tissue biopsies per patient) at St. Olav’s Hospital, Norway. Transcriptome datasets of GIM, GA, and normal tissues were compared within the same stomachs. Computational platform ScType was used for cell-type identification based on given scRNA-seq data and a comprehensive cell marker database. Ingenuity pathway analysis, Pagerank centrality, GO and MSigDB enrichments, CopyKat, aneuploid analysis, docking analysis, pathology and immunohistochemistry (IHC) were used for data and pathway mining, protein-protein interaction (PPI), and molecular structure-based drug repurposing.

Results

GIM displayed 110 canonical pathways that exhibited a negative correlation with GA. Wnt/β-catenin, ERK/MAPK, mTOR, neuregulin, and BRCA1 pathways were activated in both GIM and GA. Conversely, pathways such as HIPPO, p53, toll-like receptor, aryl hydrocarbon receptor, LPS/IL-1-mediated inhibition of RXR function, and eIF2 were inactivated in GIM but activated in GA. GIM exhibited elevated gene expression compared to GA in tumor microenvironment-related cells. Particularly, RBP2 expression and goblet cell-related gene expression were found to be restricted in GIM, but not in GA. Chromosome instability occurred mainly in GA cells with high rates of gain or loss of chromosomes 1, 7, 12, 21 (gain), and 5, 7, 8, X (loss). CD44 IHC expression was expanded from the basal part of mucosa in normal and GIM stomachs to the upper part of the mucosa in GA stomachs. PPI analysis of 865 GIM-related proteins showed seven network nodes (i.e., drug targets) including epidermal growth factor receptor (EGFR), SRC (proto-oncogene tyrosine-protein kinase), paxillin (PXN), Jun proto-oncogene (JUN), breast cancer type 1 susceptibility protein (BRCA1), tumor protein P53 (TP53 or p53), mouse double minute 2 homolog (MDM2), and CD44. These network node proteins were also shown in The Human Protein Atlas and IHC, with the exception of SRC in GA. Computational drug repurposing of approved and investigational drugs/compounds (e.g., as found on www.clinicaltrials.gov) identified the following drugs as effective for GIM: dasatinib with or without erlotinib, nilotinib, afatinib on SRC, SM1-71 on SRC, JNJ-26483327 on EGFR, Afatinib on EGFR, ingenol mebutate on protein kinase C (PKC) family, amoxapine, benoxaprofen, avobenzone, amlexanox, alprazolam, praziquantel, ibuprofen piconol, tranilast, and restoril.

Conclusion

The druggable protein network associated with GIM progression toward GA was identified. The distinct phenotypic patterns between GIM and GA might challenge the notion that GIM serves as the primary precancerous lesion in GA tumorigenesis rather than shares a common cause with tissue-resident stem cells. Further validation of the druggable protein network is needed for the development of a cost-effective surveillance program and preventive treatment of the GIM-to-GA progression.

MULTI-BIOINFORMATICS REVEALED DRUGGABLE PROTEIN NETWORK OF PROGRESSION FROM GASTRIC INTESTINAL METAPLASIA TO GASTRIC ADENOCARCINOMA

Gøran Troseth Andersen 1, Aleksandr Ianevski 2, Mathilde Resell 2, Naris Pojskic 3, Hanne-Line Rabben 2, Synne Geithus 2, Yosuke Kodama 2, Hiroyuki Tomita 4, Denis Kainov 2, Jon Erik Grønbech 5, Yoku Hayakawa 6, Timothy C. Wang 7, Chun Mei Zhao 8, Duan Chen 2

1 Norwegian University of Science and Technology, Trondheim, Norway|||St. Olav's Hospital, Trondheim, Norway|||Namsos Hospital, NamsosNor, Norway

2 Norwegian University of Science and Technology, Trondheim, Norway

3 University of Sarajevo, Sarajevo, Bosnia and Herzegovina

4 Gifu University Graduate School of Medicine, Gifu, Japan

5 Norwegian University of Science and Technology, Trondheim, Norway|||St. Olav's Hospital, Trondheim, Norway

6 Tokyo University Hospital, Tokyo, Japan

7 Columbia University Medical Center, New York, United States

8 Norwegian University of Science and Technology, Trondheim, Norway|||Central Norway Regional Health Authority, Trondheim, Norway

Conference

UEG Week Vienna 2024

Topics

Oesophagus

Submission format

Abstract

Session

Challenges in upper GI and small bowel cancer (Posters)

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

UEG Presentation

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CYTOPROTECTIVE CARBON MONOXIDE SIGNALING IS MITOCHONDRIA-ORIENTED AND ENHANCES GASTRIC MUCOSAL ABILITY TO COUNTERACT PATHOLOGY-DRIVEN DISINTEGRATION EVOKED BY NON-STEROIDAL ANTI-INFLAMMATORY DRUG

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Introduction

Carbon monoxide (CO) is an endogenous gaseous messenger produced by the enzymatic activity of heme oxygenase with anti-inflammatory and anti-oxidative properties [1]. Pharmacological CO donors with ability to release small amounts of CO exerted gastroprotective effects against injuries induced by ethanol, ischemia/reperfusion or non-steroidal anti-inflammatory drugs (NSAIDs) [2,3]. Interestingly, further studies revealed that low concentrations of CO influence mitochondrial bioenergetics and respiration by binding to heme proteins in electron transport chain (ETC), resulting in cytoprotective action [4]. Therefore, novel and unique startegy based on „click chemistry” has been invented by the Binghe Wang Lab (Georgia State University, USA) to deliver CO directly to the mitochondria [5]. However, this approach is yet to be implemented in GI pharmacology. Moreover, mitochondria as a fundamental target of endogenous CO-signaling in pathogenesis and prevention of GI pathologies has been ignored.

Aims & Methods

Therefore, we aimed to prove for the first time that mitochondrial rather than stochastic CO-signaling contributes in gastric mucosal integrity maintenance under pathogenic conditions. We also evaluated if targeted mitochondrial delivery of novel CO-prodrug described by Zheng et al. (Nature Chemistry 2018) [5] (working name: BW-mito-CO) protects gastric mucosa against acute injury evoked by NSAIDs representative, acetylsalicylic acid (ASA). Thus, male Wistar rats were pretreated intragastrically (i.g.) with 1) DMSO/H2O as vehicle, 2) BW-mito-CO (0.2, 1, 5 mg/kg) and CO-release activating „click”-moiety, 3) selected, the most effective dose of BW-mito-CO (5 mg/kg) + rotenone, a mitochondrial complex I inhibitor (5 mg/kg). Subsequently, gastric mucosal injury was induced by i.g. administration of ASA (125 mg/kg). Gastric mucosal damage and gastric mucosal blood flow (GBF) have been assessed by planimetry and laser flowmetry, respectively. Proteome profiling and molecular targets screening in gastric mucosal biopsies was performed using mass spectrometry-based proteomics. BW-mito-CO platform was synthesized in house according to Zheng et al. (Nature Chemistry 2018) [5].

Results

BW-mito-CO dose-dependently reduced the area of ASA-induced gastric mucosal damage, with the most notable effect observed at the dose of 5 mg/kg, while GBF remained without significant changes. Rotenone did not alter the protective effect of BW-mito-CO. Proteomic analysis revealed that BW-mito-CO (5 mg/kg) significantly upregulated proteins related to the tricarboxylic acid cycle and cytoprotective agents associated with gastric mucosal defense, including calpaines and treofil factor that were mostly altered in opposite manner by ASA. Pretreatment with BW-mito-CO upregulated mitochondrial complex I hemoproteins that were not affected by ASA.

Conclusion

We conclude that gastric mucosal CO-signaling mostly relies on its impact on mitochondrial compartments. Increased mitochondrial bioavailability of CO counteracts pathology-driven proteomic shifts in gastric mucosa. Implementation of mito-targeted CO delivery platforms appeared here as a novel and promising approach to GI pharmacology vs NSAIDs-induced gastric mucosal injuries. Mitochondrial CO signaling seems to mechanistically depend on its capacity to activate mitochondrial complex I and to enhance gastric mucosal ability to maintain its integrity under pathological conditions [Founding source: National Science Centre (Poland): 2019/33/B/NZ4/00616; Ministry of Science and Higher Education (Poland): Perły Nauki PN/01/0279/2022].

References

1. Yang X, Mao Q, Wang B. On the Question of CO’s Ability to Induce HO-1 Expression in Cell Culture: A Comparative Study Using Different CO Sources. ACS Chem Biol. 2024 Mar 15; 19(3): 725–735. doi:10.1021/acschembio.3c00750.
2. Danielak A, Wallace JL, Brzozowski T, et al. Gaseous Mediators as a Key Molecular Targets for the Development of Gastrointestinal-Safe Anti-Inflammatory Pharmacology. Front Pharmacol. 2021;12: 657457. doi:10.3389/fphar.2021.657457.
3. Bakalarz D, Surmiak M, Yang X, et al. Organic carbon monoxide prodrug, BW-CO-111, in protection against chemically-induced gastric mucosal damage. Acta Pharm Sin B. 2021;11(2). doi:10.1016/j.apsb.2020.08.005.
4. Iacono LL, Boczkowski J, Zini R, et al. A carbon monoxide-releasing molecule (CORM-3) uncouples mitochondrial respiration and modulates the production of reactive oxygen species. Free Radic Biol Med. 2011; 1;50(11):1556-64. doi: 10.1016/j.freeradbiomed.2011.02.033.
5. Zheng Y, Ji X, Yu B, et al. Enrichment-triggered prodrug activation demonstrated through mitochondria-targeted delivery of doxorubicin and carbon monoxide. Nat Chem. 2018;10(7). doi:10.1038/s41557-018-0055-2.

CYTOPROTECTIVE CARBON MONOXIDE SIGNALING IS MITOCHONDRIA-ORIENTED AND ENHANCES GASTRIC MUCOSAL ABILITY TO COUNTERACT PATHOLOGY-DRIVEN DISINTEGRATION EVOKED BY NON-STEROIDAL ANTI-INFLAMMATORY DRUG

Aleksandra Danielak 1, Urszula Glowacka 1, Malgorzata Szetela 1, Monika Pinkas 1, Kinga Krukowska 1, Maciej Suski 2, Beata Gryzło 1, Monika Marcinkowska 1, Marcin Magierowski 1

1 Jagiellonian University Medical College, Cracow, Poland

2 Jagiellonian University Medical College, Cracow, Poland|||Jagiellonian University Medical College, Cracow, Poland

Event

UEG Week Vienna 2024

Topics

Digestive Oncology Mechanisms & Personalised Medicine Oesophagus Stomach & H. Pylori

Submission format

Abstract

Session

Upper GI basic: Reflux, gastritis and cancer

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

UEG Standards and Guidelines

Clinical Practice Guideline

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Abstract

This is an update of the WHO SSI guideline published in 2018, focussing on areas pertinent for gastrointestinal (GI) surgery and hepatobiliary and pancreatic (HBP) surgical procedures. Based on new information and appraisal of current evidence, the following recommendations can be suggested: During skin preparation, we suggest using alcohol-based chlorhexidine for clean, clean-contaminated, and contaminated GI and HBP surgical field preparation in the absence of a mucous membrane (e.g., stoma, genitalia, anus). Preoperatively, we suggest that corticosteroids and anti-TNF medication be discontinued. No recommendations could be made on the following comparisons, given the paucity of high-quality evidence and panel discussion not favouring one intervention over the other based on clinical experience: 2%-3% chlorhexidine gluconate versus aqueous povidone-iodine for surgical field preparation. 4%-5% chlorhexidine gluconate versus aqueous povidone-iodine for surgical field preparation. Aqueous chlorhexidine gluconate versus aqueous povidone-iodine for surgical field preparation Pre-operative dexamethasone in single-dose versus no pre-operative dexamethasone for patients undergoing GI surgery. Discontinuing Vedolizumab preoperatively versus continuing Vedolizumab preoperatively for patients undergoing GI surgery. Discontinuing Ustekinumab preoperatively versus continuing Ustekinumab preoperatively for patients undergoing GI surgery.

European Guideline on Pre-Operative Prevention of Surgical Site Infections Following Digestive Surgery: A Joint Update of the WHO SSI Guideline for Gastrointestinal Surgery by UEG, ESCP, EAES, and SIS-E

Adele Sayers

Publishers

European Association for Endoscopic Surgery and other interventional techniques, European Society for Coloproctology

Guideline

Clinical Practice Guideline

Topics

Surgery

Citation

United European Gastroenterology Journal, 2025; 13:1887–1904

Published

2025

UEG Standards and Guidelines

Consensus

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ABSTRACT

Introduction

Abdominal distension is an objective visible sign of increased abdominal girth. Bloating is a feeling of abdominal fullness and discomfort. Bloating may be associated or not with abdominal distension. Bloating and abdominal distension are among the most commonly reported gastrointestinal symptoms and may be associated with both organic and functional disorders. Nevertheless, specific consensus and recommendations on diagnosis, underlying mechanisms, assessment and management of functional bloating and abdominal distension are still lacking. The aim of this European consensus, then, is to provide expert opinions and recommendations on the epidemiology, diagnosis, pathophysiology and treatment of functional bloating and abdominal distension.

Methods

A multidisciplinary team of experts in the field, including European specialists and national societies, participated in the development of this consensus. Relevant questions were formulated and addressed through a literature review and statements were developed and voted using a Delphi process.

Results

Functional bloating and abdominal distension are common and frequently overlap with other disorders of gut-brain interaction. Diagnosis is made according to the Rome IV criteria after the exclusion of organic disease, based on the physical examination and assessment of the patient's medical history and alarming signs. In the absence of alarming signs or any relevant finding, clinical laboratory, imaging or endoscopic tests are unnecessary. The pathophysiology of functional bloating and abdominal distension is multifactorial and involves visceral hypersensitivity, abdomino-phrenic dyssynergia, intestinal dysmotility and dysbiosis. Treatment may include dietary modifications (e.g. lactose-limiting diet and low FODMAP diet), probiotics, antispasmodics (e.g., otilonium bromide, peppermint oil), rifaximin, secretagogues (e.g., linaclotide), neuromodulators (e.g., serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, buspirone), and plethysmography-based biofeedback. Moreover, cognitive behaviour therapy and hypnotherapy can be used in case of functional bloating associated with irritable bowel syndrome.

Conclusion

This consensus provides an evidence-based framework for the evaluation and treatment of patients with functional bloating and abdominal distension.

European Consensus on Functional Bloating and Abdominal Distension—An ESNM/UEG Recommendations for Clinical Management

Chloé Melchior

Publisher

European Society of Neurogastroenterology and Motility

Guideline

Consensus

Topics

Neurogastroenterology & Motility

Citation

United European Gastroenterology Journal, 2025; 13:1613–1651

Published

2025

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