Gut最新文献

{"title":"Post-infection disorders of the gut: of latitude and longitude.","authors":"Kok Ann Gwee","doi":"10.1136/gutjnl-2025-337808","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-337808","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":"55 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147381276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimising mono-antibiotic eradication regimen by potent acid inhibitor and bismuth: a potential solution to rising clarithromycin resistance in Helicobacter pylori.","authors":"Yu-Hwa Liu,I-Ting Wu,Tzung-Jiun Tsai,Ping-I Hsu,Deng-Chyang Wu,John Kao","doi":"10.1136/gutjnl-2026-338544","DOIUrl":"https://doi.org/10.1136/gutjnl-2026-338544","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":"56 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147368236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination therapies for metabolic dysfunction-associated steatohepatitis: challenges and opportunities.","authors":"Xiao-Dong Zhou, Qiong-Yue Fan, Christopher D Byrne, Giovanni Targher, Mark D Muthiah, Daniel Q Huang, Qin-Fen Chen, Mazen Noureddin, Wenhao Li, Vlad Ratziu, Rohit Loomba, Sven M Francque, Arun J Sanyal, Ming-Hua Zheng","doi":"10.1136/gutjnl-2025-337431","DOIUrl":"10.1136/gutjnl-2025-337431","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatohepatitis (MASH) is a multifactorial metabolic liver disease that occurs in the context of obesity, insulin resistance and cardiometabolic comorbidities. Monotherapy targeting single pathways often provides only partial improvements in histological liver fibrosis and systemic metabolic parameters, prompting growing interest in multitargeted combination therapies. Multitargeted and combination strategies for MASH can modulate multiple and complementary pathogenic processes, potentially improving efficacy, promoting liver fibrosis regression, optimising systemic metabolic outcomes and reducing treatment-related adverse effects. Liver-directed combination therapies, such as thyroid hormone receptor-beta (THR-β) agonists along with acetyl-CoA carboxylase (ACC) inhibitors or peroxisome proliferator-activated receptor agonists, aim to improve histological features of MASH. Regimens combining systemic metabolic and liver-specific agents, such as glucagon-like peptide-1 (GLP-1) receptor agonists with fibroblast growth factor-21 analogues or THR-β agonists, aim to optimise metabolic outcomes, including body weight, insulin resistance and plasma lipids. Thoughtfully designed drug pairings, such as diacylglycerol O-acyltransferase 2 inhibitors combined with ACC inhibitors or GLP-1 and glucagon receptor dual agonists, could improve safety and tolerability by leveraging complementary mechanisms that may mitigate adverse effects. These therapeutic strategies aim to achieve more comprehensive and durable improvements in both liver pathology and systemic health than single-agent therapy alone. This review integrates current knowledge on multitargeted and combination therapies for MASH, examines mechanistic rationales and emerging clinical evidence and addresses practical considerations for patient-centred implementation. Therefore, we aim to provide clinicians and researchers with a comprehensive framework to optimise individualised management and improve both hepatic and systemic outcomes in individuals living with MASH.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"815-825"},"PeriodicalIF":25.8,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel insights into autoimmune gastritis: clinical profile and gastric neoplastic risk from an international multicentre study.","authors":"Marco Vincenzo Lenti,Emanuela Miceli,Irfan Soykan,Arnoldo Riquelme,Gonzalo Latorre,Marcia R Cruz-Correa,Olga L Díaz-Miranda,Hilmaris Centeno-Girona,Ingrid M Montes-Rodríguez,Maria Gonzalez-Pons,Ken Haruma,Peter Malfertheiner,Marino Venerito,Julian-Yannick Baur,Monika Laszkowska,Vivian E Strong,Tamara Matysiak-Budnik,Amaury Druet,Nicolas Chapelle,Jerome Martin,Shailja C Shah,Mārcis Leja,Sara Massironi,Edith Lahner,Bruno Annibale,Alessandra Bonfichi,Gabriele Natalello,Carmine Frenna,Clarissa Petrucci,Andrea Quadrelli,Mariangela Delliponti,Marco Paulli,Alessandro Vanoli,Shamim Joudaki,Francisca Venezian,Juan Carlos Roa,Sara Maquilon,Alberto Espino,Jose Ignacio Vargas,Elena M De Giorgi,Valeria Musella,Gino Roberto Corazza,Catherine Klersy,M Constanza Camargo,Antonio Di Sabatino","doi":"10.1136/gutjnl-2025-337458","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-337458","url":null,"abstract":"BACKGROUNDInternational comparative data on autoimmune gastritis (AIG) remain limited.OBJECTIVEWe aimed to describe AIG features and quantify the risk of gastric adenocarcinoma and type 1 gastric neuroendocrine tumours (NETs).DESIGNRetrospective study across eight tertiary centres in Europe, Türkiye, Latin America, the USA and Japan. Adults with histologically confirmed AIG were included. Clinical and follow-up data were collected to estimate adenocarcinoma and NET incidence and associated factors.RESULTS1240 patients were included (female:male 2:1; median age 59, IQR 48-67; median follow-up 68 months, IQR 36-108). Macrocytic anaemia predominated in Europe (45.6%), microcytic anaemia in Türkiye (56.1%) and Latin America (64.7%). Autoimmune comorbidities were most frequent in Latin America (67.7%). 36 (2.9%) gastric adenocarcinomas and 132 (10.6%) NETs occurred. No incident adenocarcinomas were reported in Latin America or Japan cohorts. Crude incidence rates ranged from 1.15 to 1.47 for adenocarcinoma and 0.70 to 1.62/100 person-years for NETs. Factors associated with adenocarcinoma included age >65 years (OR 4.50, 95% CI 2.18 to 9.27), intestinal metaplasia (OR 1.51, 95% CI 1.16 to 1.97), gastrin-17 >1316 pg/mL (OR 15.52, 95% CI 3.61 to 66.71) and prior proton pump inhibitor (PPI) (OR 5.74, 95% CI 2.13 to 15.47). For NETs, prior PPI (OR 2.69, 95% CI 1.12 to 6.46), smoking (OR 2.45, 95% CI 1.75 to 3.42), intestinal metaplasia (OR 2.88, 95% CI 1.38 to 6.01) and gastrin-17 >1316 pg/mL (OR 3.25, 95% CI 1.42 to 7.45), were associated with higher odds, while Helicobacter pylori eradication was associated with lower odds of NETs (OR 0.25, 95% CI 0.07 to 0.88).CONCLUSIONAIG presentation and neoplastic risks differ by region, warranting further research and potentially region-specific follow-up strategies.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"47 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147368237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coeliac disease and the intestinal barrier: mechanisms of disruption and strategies for restoration.","authors":"John A Damianos, Adam Bledsoe, Michael Camilleri, Joseph A Murray","doi":"10.1136/gutjnl-2025-335373","DOIUrl":"10.1136/gutjnl-2025-335373","url":null,"abstract":"<p><p>Coeliac disease is characterised by immune-mediated damage to the small intestine in response to dietary gluten in genetically predisposed individuals. Increased intestinal permeability is a central component to its pathophysiology. This review explores the evidence for increased permeability in coeliac disease and the underlying mechanisms, including the roles of zonulin, inflammatory cytokines, microbial alterations and immune responses to gliadin peptides. We also review comprehensively the therapies targeting barrier integrity and normalising intestinal permeability, including particular diets and supplements, and experimental and improved medications including larazotide acetate and IMU-856. Finally, we highlight the need for reliable biomarkers for evaluating increased permeability in coeliac disease and advocate for further research on therapies which normalise barrier function, particularly as a strategy to maintain remission.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"826-838"},"PeriodicalIF":25.8,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nucleotide analogue bemnifosbuvir inhibits hepatitis E virus replication in preclinical models.","authors":"Jungen Hu,Tianxu Liu,Mara Klöhn,Andrew Freistaedter,Elif Toprak,Huanting Chi,André Gömer,Lilli Pottkaemper,Paula Jordan,Xinyue Yang,He Zhang,Johanna Becker,Shirin Nkongolo,Volker Lohmann,Eike Steinmann,Lin Wang,Viet Loan Dao Thi","doi":"10.1136/gutjnl-2025-336714","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-336714","url":null,"abstract":"BACKGROUNDHepatitis E virus (HEV) infections remain a global health concern. Immunocompromised patients are at an increased risk of developing chronic HEV infection and thereby severe liver disease. Current off-label regimens are suboptimal with treatment failure being reported. Therefore, there is an urgent need for an effective anti-HEV treatment.OBJECTIVEIn this study, we aimed to identify potent inhibitors of HEV replication.DESIGNWe developed a rapid, image-based screening platform based on a full-length HEV fluorescence reporter virus and screened a nucleotide/nucleoside analogue library. The identified lead candidate was validated in authentic hepatocyte culture systems, as well as in a gerbil infection model.RESULTSBemnifosbuvir (BEM), previously characterised as a nucleotide analogue with activity against other RNA viruses, efficiently suppressed HEV replication in vitro and in vivo in a dose-dependent manner, with minimal cytotoxicity at effective concentrations. Combining BEM with ribavirin, the off-label drug given to patients with chronic HEV, resulted in an additive antiviral effect against HEV. We found that HEV-3 remains susceptible to inhibition by BEM over an extended treatment period, reducing concerns about the rapid development of viral resistance. Importantly, BEM significantly reduced HEV viral loads and liver inflammation in a gerbil infection model.CONCLUSIONSGiven BEM's favourable safety profile in preclinical and clinical settings, our results suggest investigating its efficacy in patients with chronic HEV infection.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"9 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147368267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: <i>Patient-derived organoid biobank identifies epigenetic dysregulation of intestinal epithelial MHC-I as a novel mechanism in severe Crohn's Disease</i>.","authors":"","doi":"10.1136/gutjnl-2024-332043corr1","DOIUrl":"10.1136/gutjnl-2024-332043corr1","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"e6"},"PeriodicalIF":25.8,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146219388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiome signatures in colorectal neoplasia: a cross-sectional study across neoplasia stages and subtypes.","authors":"Panayiotis Louca,Sarah Manning,Eleanor Hackney,Linda Sharp,Mark A Hull,Sara Koo,Gregory R Young,Guy S Taylor,Yashvee Dunneram,Suparna Mitra,James S Hampton,Christina Dobson,Laura J Neilson,Caroline Addison,Emad M El-Omar, ,Christopher J Stewart,Colin J Rees","doi":"10.1136/gutjnl-2025-337478","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-337478","url":null,"abstract":"BACKGROUNDWhile colorectal cancer (CRC) has been linked to the gut microbiome, it remains unclear whether specific microbial signatures are detectable in precursor lesions such as adenomatous polyps, serrated lesions or sessile serrated lesions.OBJECTIVETo assess gut microbiome taxonomic and functional associations with colorectal neoplasia presence, severity (non-advanced, advanced and CRC) and subtype and evaluate predictive potential in high-risk neoplasia.DESIGNAnalysed cross-sectional stool metagenomes (pre-colonoscopy) from 1762 participants (97% White British) undergoing colonoscopy in the multicentre COLO-COHORT study. Neoplasia was classified per British Society of Gastroenterology surveillance guidelines. Linear mixed-effects models and random forest classifiers assessed taxonomic and functional associations, adjusting for dietary, clinical and lifestyle covariates.RESULTSGut microbiome composition differences between individuals with and without neoplasia were statistically significant but minimal (R2=0.0008, p=0.03). A small number of species, including Mediterraneibacter faecis and Pseudoruminococcus massiliensis, and microbial pathways, including amino acid biosynthesis and β-lactam resistance, were modestly linked to neoplasia, particularly early lesions (q value <0.05). Associations were generally weak and attenuated after covariate adjustment. Predictive models combining the microbiome with clinical/demographic features modestly improved high-risk neoplasia classification (area under the curve=0.64 vs 0.58 for clinical/demographic features alone).CONCLUSIONThis large prospective cross-sectional study found weak and inconsistent associations between the gut microbiome and premalignant colorectal neoplasia, with no robust microbial signatures. Findings suggest that previously reported microbial shifts may emerge later in disease progression, potentially as a consequence rather than a cause of CRC. Longitudinal, multiomic studies disentangling temporal and causal pathways between the gut microbiome and neoplasia are required.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"15 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147368235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: <i>Congenital sucrase-isomaltase mutations worsen IBS-linked V15F dysfunction and trafficking</i>.","authors":"","doi":"10.1136/gutjnl-2025-336813corr1","DOIUrl":"10.1136/gutjnl-2025-336813corr1","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"e5"},"PeriodicalIF":25.8,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146226554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High versus gradually increasing energy nutrition in the early phase of acute pancreatitis (GOULASH): a multicentre double-blind randomised clinical trial.","authors":"Katalin Márta,Marie Anne Engh,Áron Vincze,Bálint Erőss,Péter J Hegyi,Alexandra Mikó,Ferenc Izbéki,Mária Papp,Péter Mátrai,Zsolt Abonyi-Tóth,Nándor Faluhelyi,Andrea Szentesi,Péter Hegyi, ","doi":"10.1136/gutjnl-2025-335970","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-335970","url":null,"abstract":"BACKGROUNDAcute pancreatitis (AP) is among the most common gastrointestinal diseases requiring hospitalisation, often with severe outcomes and no disease-specific therapy. Nutritional support has been proven to improve outcome, but little is known regarding optimal timing and composition.OBJECTIVEThis clinical trial aimed to compare high (30 kcal/kg/day, high energy (HE)) versus gradually increasing energy (0 increased to 30 kcal/kg/day over 4 days, low energy (LE)) strategies for enteral nutritional support in AP.DESIGNThis was a multicentric, double-blind, randomised clinical trial, enrolling patients with AP regardless of predicted severity (January 2017 to April 2023). The primary outcome was a combination of mortality and severe acute pancreatitis (Revised Atlanta Criteria); secondary outcomes included severity, rate of infection, organ failure and pain relapse. Interim analysis was planned after 50% enrolment. The Benjamini-Hochberg false discovery rate (FDR) method was used to correct p value for multiple testing.RESULTSThe trial was stopped early after enrolling 636 patients. Interim analysis showed that the primary outcome showed no difference between groups in the modified intention-to-treat (mITT) population (HE: 28/312, 9.0% vs LE: 18/307, 5.7%, p(uncorrected/corrected)=0.19/0.42). Secondary outcomes showed no difference in the mITT analysis. Without correction for multiplicity testing, results favoured a low gradual energy strategy in terms of organ failure (HE: 52/312, 16.7% vs LE: 28/307, 9.1%, p(uncorrected)=0.007) and pain relapse (80/312, 27.1% vs 54/307, 19.0% p(uncorrected)=0.03) but showed no differences between groups after correction for multiple testing (p=0.13 and p=0.23, respectively). It was determined that the superiority of the intervention would not be shown even with an increased sample size, and thus the trial was terminated based on a post hoc decision on ethics and futility.CONCLUSIONBased on this early terminated trial, a high-energy strategy for early nutrition in pancreatitis does not decrease mortality/severity, but potentially increases organ failure and pain relapse rate.TRIAL REGISTRATION NUMBERISRCTN63827758.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"32 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147359009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}