Gut最新文献

{"title":"Offspring MASLD risk and the shared familial metabolic milieu: beyond intrauterine explanation.","authors":"Jithin J Chandran,Naveen Bhagat,Arka De,Ajay Duseja","doi":"10.1136/gutjnl-2026-338827","DOIUrl":"https://doi.org/10.1136/gutjnl-2026-338827","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":"114 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147702156","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":"Circulating extracellular vesicle long RNA profiling combined with machine learning unveils novel diagnostic signature and molecular features in chronic pancreatitis.","authors":"Yu Cao,Jia Hu,Jun Ye,Duowu Zou,Zheng Wang,Tao Yin,Wanxing Duan,Xuesong Liang,Jinying Chen,Yuchen Li,Hongyan Lai,Shulin Yu,Zhen Wang,Yahui Wang,Peng Wang,Zhaoshen Li,Wenbin Zou,Shenglin Huang,Zhuan Liao","doi":"10.1136/gutjnl-2025-335957","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-335957","url":null,"abstract":"BACKGROUNDNo clinically useful non-invasive biomarkers have been developed for diagnosis of chronic pancreatitis (CP), and molecular features of CP have not been characterised. Extracellular vesicles (EVs) consisted of abundant RNA species with specialised functions and clinical applications.OBJECTIVEOur study aimed to construct a diagnostic model for CP and depict molecular landscape of CP based on EV long RNA (ExLR).DESIGNCandidate ExLRs were defined using prespecified expression-quality criteria and complementary discovery-stage screens, and a resampling-based consensus feature selection in the training cohort yielded a five-ExLRs panel for model construction. The ExLRs-based CP diagnostic model (ExLRCPdscore) was further confirmed in another two independent validation cohorts with different controls. To elucidate the biological architecture of CP through ExLR profiling, we integrated ExLR-seq, single-cell data and clinical information.RESULTSExLRCPdscore constructed by random forest demonstrated excellent performance for detecting CP. Importantly, ExLRCPdscore could effectively detect early-stage CP, CP without alarm symptoms, CP without significant imaging findings and CP without risk factors. Using ExLR profiling and phenotypic data, we pinpointed MUC5B+ ductal cells exhibiting the strongest correlation with CP and derived an ExLR-based acinar-to-ductal metaplasia (ADM) score as a blood-based transcriptomic proxy of ADM-related programme. Integration of ExLR-seq and clinical information revealed significant associations between ADMscore and clinical characteristics, imaging findings and metabolic sequelae.CONCLUSIONOur study is the first to report an ExLRs-based diagnostic model that demonstrates exceptional robustness in differentiating CP from healthy controls and non-pancreatic disease controls. ExLRs offer a promising tool for CP molecular characterisation and pathophysiological quantification.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"13 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147695153","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":"Targeting PKM2-dependent glycolysis reprogrammes monocytes into Cadm1+ macrophages to promote mucosal repair and attenuate colitis progression.","authors":"Di Zhang,Ping Tao,Jinying Li,Xingyan Zhou,Hengdong Qu,Yaobin Li,Haoxian Chen,Hui Yuan,Jiabin Huang,Ziyi Ji,Pengqing Sun,Haoting Lin,Keke Zhang,Wei Huang,Huixin Chen,Wencai Ye,Jian Hong","doi":"10.1136/gutjnl-2025-337344","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-337344","url":null,"abstract":"BACKGROUNDIncomplete mucosal healing contributes to progression and relapse in ulcerative colitis (UC). Currently, therapeutic strategies that promote mucosal healing and regeneration are limited and may potentiate oncogenic transformation.OBJECTIVEWe aimed to identify whether modulating macrophage metabolism may facilitate mucosal healing without driving tumourigenesis.DESIGNPotential therapeutic targets associated with UC disease activity and relapse were assessed in multiple omics datasets and three clinical UC studies. The function and mechanism of macrophage pyruvate kinase M2 (PKM2) in UC progression were demonstrated by macrophage-specific PKM2 knockout mice, single-cell and spatial transcriptomic profiling, and human macrophage-colonic organoid coculture models.RESULTSGlycolysis was markedly upregulated in intestinal macrophages within damaged regions in UC patients, whereas PKM2 expression was associated with increased disease severity and a greater incidence of relapse. PKM2 depletion in macrophages enhanced intestinal barrier function and ameliorated colitis progression in mice. Mechanistically, PKM2 deficiency promoted monocyte differentiation into reparative Cadm1+ macrophages and enhanced Lgr5+ stem cell self-renewal via the PGE2/EP4 axis. Cross-species analysis revealed that human STAB1+ macrophages, which exhibit transcriptomic and metabolic similarities to mouse Cadm1+ macrophages, were positively associated with UC remission and spatial distribution of CD8+ T cells in colorectal cancer. Interestingly, macrophage PKM2 deletion greatly suppressed tumourigenesis in mice, accompanied by an increased abundance of Cadm1+ macrophages and enhanced CD8+ T-cell infiltration. Furthermore, targeting PKM2 in intestinal macrophages attenuated colitis progression in mice.CONCLUSIONSTherapeutic targeting of PKM2-dependent glycolysis in macrophages enhanced Cadm1+ macrophage-mediated mucosal healing without driving tumourigenesis.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"98 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147684809","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":"Percutaneous needle decompression for endoscopic iatrogenic pneumoperitoneum: assessment of safety and efficacy in real world practice.","authors":"Trent Walradt, Daniel Szvarca, Jonathan Melendez Torres, Christopher C Thompson","doi":"10.1136/gutjnl-2026-338174","DOIUrl":"https://doi.org/10.1136/gutjnl-2026-338174","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":25.8,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147689858","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":"CD16+ γδ T cells mediate antibody-dependent cellular cytotoxicity and associate with viral control in chronic hepatitis B virus infection.","authors":"Paulina E Schröter,Katja Steppich,Laura Fernández Carrera,Zheng Song,Sebastian Klein,Roni Souleiman,Melanie Urbanek-Quaing,Ayesha D Lietzau,Ansgar Schnieders,Erich Freyer,Birgit Bremer,Ximena León-Lara,Vicente Almeida,Rodrigo Gutierrez Jauregui,Constantin Von Kaisenberg,Matthias Bruhn,Carla Meineke,Ulrich Kalinke,Heiner Wedemeyer,Immo Prinz,Sarina Ravens,Arnaud Carpentier,Yannic Christoph Bartsch,Anke R M Kraft,Markus Cornberg","doi":"10.1136/gutjnl-2025-337640","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-337640","url":null,"abstract":"BACKGROUNDChronic hepatitis B virus (HBV) infection is characterised by immune dysfunction. While conventional T cell responses have been extensively studied, the role of γδ T cells, innate-like cytotoxic lymphocytes enriched in the liver, remains incompletely understood.OBJECTIVETo characterise γδ T cell subsets in HBV infection and assess their association with viral control and antibody-dependent cellular cytotoxicity (ADCC).DESIGNPeripheral blood from patients with chronic (n=83) and acute (n=16) HBV infection, healthy controls (n=31), and cord-blood donors (n=3) was analysed using multiparameter flow cytometry, single-cell RNA sequencing and in vitro ADCC assays.RESULTSA distinct CD16+ γδ T cell subset inversely correlated with hepatitis B core-related antigen (HBcrAg), a surrogate of intrahepatic viral replication. CD16+ γδ T cells displayed a cytotoxic signature, whereas CD16⁻ cells showed inflammatory, non-cytotoxic profiles. On hepatitis B surface antigen-specific antibody stimulation, CD16+ γδ T cells mounted potent ADCC responses, mainly mediated by Vδ2+ cells expressing the activating receptor CD226, while Vδ1+ cells preferentially expressed the inhibitory receptor TIGIT. Cytotoxic CD16+ Vδ2+ γδ T cells were present in both blood and liver. CD16+ γδ T cells were expanded and highly functional in acute HBV but reduced and partially impaired in chronic infection. Neonatal cord-blood-derived γδ T cells lacked CD16 expression and displayed limited ADCC potential.CONCLUSIONSCD16+ γδ T cells mediate antibody-dependent antiviral immunity in HBV infection. Their inverse association with HBcrAg links γδ T cell-mediated ADCC to viral control and highlights this pathway as a target for HBV cure strategies.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"38 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147684812","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":"Loss of sinusoidal endothelial identity: RAP1A at the crossroads of capillarisation and liver fibrosis.","authors":"Isabel Fabregat,Christian David Schmid","doi":"10.1136/gutjnl-2026-338383","DOIUrl":"https://doi.org/10.1136/gutjnl-2026-338383","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":"56 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147684807","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":"Stromal biomarker-based framework for identifying pMMR/MSS and dMMR/MSI colorectal cancers with poor outcomes and limited benefit from immunotherapy.","authors":"Mar Iglesias Coma,Jordi Badia-Ramentol,Carolina Martinez-Ciarpaglini,Jenniffer Linares,Noelia Tarazona,Nuria Mulet-Margalef,Paula Tornero-Piñero,Anna Sallent-Aragay,Alba Recort-Bascuas,Joan Gibert,Marta Sant-Albors,Daniele V F Tauriello,Melba Cruz-Moral,Marina Carreras-Gallardo,Elena Sancho,Clara Morral Martinez,Marta Garrido,Jose Luis Manzano Mozo,Andrés Cervantes,Clara Montagut,Eduard Batlle,Alexandre Calon","doi":"10.1136/gutjnl-2025-336804","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-336804","url":null,"abstract":"BACKGROUNDColorectal cancer (CRC) remains a leading cause of cancer mortality worldwide, with clinical progress limited by intratumoural cellular diversity and the absence of robust, informative markers.OBJECTIVELeveraging the heterogeneity of cancer-associated fibroblasts (CAFs) within the tumour microenvironment, this study aims to identify and evaluate candidate biomarkers to support patient stratification and improve prediction of therapeutic responses.DESIGNWe applied a multiomic approach integrating single-cell RNA sequencing, computational cell deconvolution and protein-level assessment from patient tumours, complemented by in vitro and in vivo preclinical models, to characterise stromal populations linked to CRC progression and treatment resistance.RESULTSRetrospective analysis of over 3000 patient samples across multiple cohorts identified a distinct subset of CAFs expressing collagen triple helix repeat containing 1 (CTHRC1). CTHRC1(+) CAFs were associated with increased transforming growth factor-beta (TGF-beta) signalling and poor clinical outcomes in early and advanced disease stages. CTHRC1(+) CAFs enabled stratification of both mismatch repair-deficient/microsatellite instability (dMMR/MSI) and mismatch repair-proficient/microsatellite stability (pMMR/MSS) tumours into immune-inflamed and poorly immunogenic subtypes. Retrospective analysis of several clinical trials revealed that CTHRC1(+) CAFs are linked to resistance to immune checkpoint inhibitors in MSI and MSS tumours, suggesting therapeutic potential for combining TGF-beta blockade with immunotherapy.CONCLUSIONCTHRC1-expressing CAFs represent clinically relevant biomarkers that link molecular profiling with diagnostic pathology. Our findings support the potential incorporation of CTHRC1(+) CAF assessment into routine histopathological workflows, pending prospective validation, and suggest a framework for stroma-informed CRC stratification, particularly in patients with stroma-rich, treatment-resistant tumours and pMMR/MSS with limited therapeutic options.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"10 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147680705","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":"Proton pump inhibitors should be continued after endoscopic variceal ligation.","authors":"Abhishek Yadav,Harshal Surendra Mandavdhare,Vishal Sharma,Atul Saroch,Jimil Shah,Nitin Jagtap,Anupam Kumar Singh,Jayanta Samanta,Vaneet Jearth,Usha Dutta,Saroj Kant Sinha","doi":"10.1136/gutjnl-2026-338098","DOIUrl":"https://doi.org/10.1136/gutjnl-2026-338098","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":"44 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147680703","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":"<i>Tff2</i> marks gastric corpus progenitors that give rise to pyloric metaplasia/SPEM following injury.","authors":"Ruhong Tu, Hua-Long Zheng, Biyun Zheng, Qing Zhong, Jin Qian, Qian Yu, Feijing Wu, Toshiro Shiokawa, Yosuke Ochiai, Hiroki Kobayashi, Quin T Waterbury, Leah Zamechek, Youxin Gao, Satoru Takahashi, Seiya Mizuno, Chang Ming Huang, Ping Li, Yoku Hayakawa, Timothy C Wang","doi":"10.1136/gutjnl-2025-337839","DOIUrl":"10.1136/gutjnl-2025-337839","url":null,"abstract":"<p><strong>Background: </strong>Spasmolytic polypeptide-expressing metaplasia (SPEM) arises in the gastric corpus in response to oxyntic atrophy, but its cellular origin and role in gastric cancer remain unclear.</p><p><strong>Objective: </strong>To define the cellular origin of SPEM in the gastric corpus and its relationship to gastric dysplasia and cancer progression.</p><p><strong>Design: </strong><i>Tff2-CreERT2</i> knock-in mice were used for lineage tracing and genetic ablation to characterise Tff2⁺ corpus progenitor cells. Acute injury, chief cell ablation, <i>H. pylori</i> infection and Kras^G12D activation models were applied. Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics were performed on human gastric tissues to validate differentiation trajectories.</p><p><strong>Results: </strong>Highly proliferative Tff2⁺ progenitors were localised to the corpus isthmus and generated multiple secretory lineages including chief cells, but lacked long-term self-renewal. Following acute injury or chief cell loss, Tff2⁺ progenitors rapidly expanded to form transient SPEM. Genetic ablation of Tff2⁺ progenitors abolished SPEM formation, whereas ablation of Lgr5-DTR- or Gif-rtTA-labelled chief cells enhanced SPEM derived from Tff2⁺ progenitors. on <i>H. pylori</i> infection or Kras^G12D activation, Tff2⁺ progenitors progressed to SPEM and dysplasia. Kras activation in Tff2⁺ progenitors promoted direct progression to dysplasia through acquisition of stem cell-like properties. In contrast, Kras-mutant SPEM and chief cells failed to progress to dysplasia. Human scRNA-seq and spatial transcriptomics revealed distinct differentiation trajectories from isthmus proliferating cells to SPEM or gastric cancer.</p><p><strong>Conclusions: </strong>Tff2⁺ corpus progenitors represent a common cellular origin for SPEM and gastric dysplasia, challenge the conventional stepwise model of gastric carcinogenesis and indicate divergent differentiation programmes from Tff2⁺ progenitors.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":25.8,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147689845","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":"Tryptophan depletion generates hyper-reactive portal neutrophils in alcoholic liver disease.","authors":"Sara Reinartz Groba,Mathis Richter,Dennis Schwarz,Philipp Seyfried,Kristian Serafimov,Xiaoqing Fu,Luca Farinola,Jan-Niklas Heming,Max Masthoff,Michael Köhler,Alexander Zarbock,Yahya Sohrabi,Michael Praktiknjo,Angelika S Rambold,Raphael Chevre,Michael Lämmerhofer,Jonel Trebicka,Oliver Soehnlein","doi":"10.1136/gutjnl-2025-337646","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-337646","url":null,"abstract":"BACKGROUNDNeutrophils guarantee a prompt and robust host response to pathogens. Yet, overshooting neutrophil activation leads to tremendous collateral damage in tissues. In advanced chronic liver disease (ACLD), neutrophils are exposed to the highly immunogenic milieu of the portal circulation prior to entering the liver sinusoids. In alcohol-related liver disease (ALD), neutrophils occupy a central role and therefore mechanisms regulating neutrophil activity pose a possible therapeutic target.OBJECTIVEEvaluate the impact of the portal milieu on neutrophils in ACLD with portal hypertension.DESIGNWe conducted a prospective study of patients undergoing transjugular intrahepatic portosystemic shunt placement. Paired blood samples were obtained from the portal vein (PV) and superior vena cava (SVC); the neutrophil phenotype was assessed by spectral flow cytometry; plasma was analysed by cytokine quantification, reporter assays and metabolomics. Effects of tryptophan supplementation on neutrophil function and phenotype were tested in isolated neutrophils.RESULTSPatients with ALD but not non-ALD showed highly activated CD10highCD11bhigh neutrophils in the portal circulation. PV plasma induced this phenotype in SVC neutrophils. Analysis of portal plasma revealed no differences in cytokines or toll-like receptor (TLR)/nucleotide-binding oligomerisation domain-containing protein (NOD) ligands but decreased local tryptophan concentrations in patients with ALD. In vitro supplementation of tryptophan ameliorated activation of isolated neutrophils.CONCLUSIONOur findings identify portal tryptophan as a local regulator of neutrophil activation in ACLD. The link between low tryptophan levels and heightened neutrophil reactivity, especially in ALD, underscores the role of the gut-liver metabolic crosstalk in immune modulation and highlights a potential therapeutic target for mitigating neutrophil-driven liver injury.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"10 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147655679","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}