Background: Chronic stress is a known risk factor for cancer metastasis. However, the underlying mechanisms, particularly those involving the gut microbiota and their metabolites, remain unclear.
Objective: To investigate whether gut microbiota dysbiosis and metabolic alterations mediate the sustained pro-metastatic effects of chronic stress, even after normalisation of stress hormone levels.
Design: Multiple metastatic models were performed after stress cessation. Shotgun metagenomics and metabolomics were performed to assess changes in microbiota and metabolites. The effects of Bifidobacterium animalis and oleic acid (OA) on metastasis were evaluated in vivo and in vitro. Moreover, we explored how B. animalis degraded OA. Mechanistically, we discovered the interaction between corticosteroids and gut bacteria through guanine metabolism assays. Human samples were collected from patients with colorectal cancer (CRC) with varying perceived stress scores and metastatic status for validation.
Results: Mice that underwent chronic stress exhibited increased metastasis even after hormone levels recovered. The gut microenvironment was altered, with a significant reduction in B. animalis and an increase in OA. B. animalis administration reduced OA levels and suppressed metastasis, while OA supplementation had the opposite effect. B. animalis expresses oleate hydratase, an enzyme that degrades OA. Stress hormones inhibited B. animalis by altering guanine metabolism in the intestinal epithelium. In patients, high stress was associated with more OA, lower B. animalis levels and increased metastasis.
Conclusions: Chronic stress promotes metastasis by altering microbiota and increasing OA. Targeting B. animalis and OA may help prevent stress-related tumour progression.
{"title":"Gut microbe alleviates stress-related cancer metastasis by oleic acid degradation.","authors":"Chen Liu, Junli Gong, Zhanhao Luo, Peng Lai, Shuang Guo, Dayi Liang, Guangyuan Chen, Mengze Xing, Jing Yu, Yanchun Xie, Danling Liu, Wanyi Zeng, Zhen He, Ping Lan","doi":"10.1136/gutjnl-2025-335627","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-335627","url":null,"abstract":"<p><strong>Background: </strong>Chronic stress is a known risk factor for cancer metastasis. However, the underlying mechanisms, particularly those involving the gut microbiota and their metabolites, remain unclear.</p><p><strong>Objective: </strong>To investigate whether gut microbiota dysbiosis and metabolic alterations mediate the sustained pro-metastatic effects of chronic stress, even after normalisation of stress hormone levels.</p><p><strong>Design: </strong>Multiple metastatic models were performed after stress cessation. Shotgun metagenomics and metabolomics were performed to assess changes in microbiota and metabolites. The effects of <i>Bifidobacterium animalis</i> and oleic acid (OA) on metastasis were evaluated <i>in vivo</i> and <i>in vitro</i>. Moreover, we explored how <i>B. animalis</i> degraded OA. Mechanistically, we discovered the interaction between corticosteroids and gut bacteria through guanine metabolism assays. Human samples were collected from patients with colorectal cancer (CRC) with varying perceived stress scores and metastatic status for validation.</p><p><strong>Results: </strong>Mice that underwent chronic stress exhibited increased metastasis even after hormone levels recovered. The gut microenvironment was altered, with a significant reduction in <i>B. animalis</i> and an increase in OA. <i>B. animalis</i> administration reduced OA levels and suppressed metastasis, while OA supplementation had the opposite effect. <i>B. animalis</i> expresses oleate hydratase, an enzyme that degrades OA. Stress hormones inhibited <i>B. animalis</i> by altering guanine metabolism in the intestinal epithelium. In patients, high stress was associated with more OA, lower <i>B. animalis</i> levels and increased metastasis.</p><p><strong>Conclusions: </strong>Chronic stress promotes metastasis by altering microbiota and increasing OA. Targeting <i>B. animalis</i> and OA may help prevent stress-related tumour progression.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145648365","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}
BACKGROUNDEndometriosis is a debilitating gynaecological disorder with an elusive pathogenesis. While gut microbiota dysbiosis has been implicated, the causal role of gut-peritoneum microbial translocation and the specific mechanisms driving disease progression remain elusive. Notably, the role of peritoneal neutrophils and neutrophil extracellular traps (NETs) in the development of endometriosis remains unknown.OBJECTIVEThis study aims to delineate the pathogenic pathway linking gut microbiota to peritoneal neutrophil activation and the development of endometriosis.DESIGNWe combined single-cell RNA sequencing of clinical peritoneal fluid immune cells with functional validation in heterologous and homologous mice models. We further adopted microbial source-tracking analysis of patient cohorts and interventional strategies, including faecal microbiota transplantation (FMT) and administration of green fluorescent protein (GFP)-tagged Pseudomonas aeruginosa.RESULTSWe identified a unique membrane metalloendopeptidase (MME) positive neutrophil subset (Neu_MME) that is expanded in endometriosis and primed for NETs formation (NETosis). These Neu_MME released NETs in response to bacterial lipopolysaccharides (LPS), which directly captured endometrial cells and enhanced their proliferation and migration, driving lesion development. Accordingly, inhibiting NETosis or degrading NETs significantly suppressed endometriosis in mice. Furthermore, FMT from patients with endometriosis to mice disrupted the intestinal barrier, promoting the translocation of gut microbiota, particularly Pseudomonas, into the peritoneal cavity and the lesions. This translocated Pseudomonas was identified as a key driver of LPS-induced NETosis and disease progression.CONCLUSIONOur findings define a gut-peritoneum axis in endometriosis, where gut-derived Pseudomonas triggers NETosis in peritoneal Neu_MME to promote disease, suggesting that targeting this bacterium or NETosis represents a viable therapeutic strategy.
{"title":"Intraperitoneal translocation of gut microbiota induces NETosis and promotes endometriosis.","authors":"Xiangguang Wu,Mingfu Wu,Huawen Li,Yang Yang,Huimin Shen,Siyuan Huang,Yuha Pan,Liwen Tao,Shuangshuang Guo,Jinjiao Chen,Yu Wu,Xiaoqing Zhong,Shuangdi Li,Binya Liu,Wenliang Zhang,Ruixin Zhu,Liangsheng Fan,Wei Wang","doi":"10.1136/gutjnl-2025-336185","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-336185","url":null,"abstract":"BACKGROUNDEndometriosis is a debilitating gynaecological disorder with an elusive pathogenesis. While gut microbiota dysbiosis has been implicated, the causal role of gut-peritoneum microbial translocation and the specific mechanisms driving disease progression remain elusive. Notably, the role of peritoneal neutrophils and neutrophil extracellular traps (NETs) in the development of endometriosis remains unknown.OBJECTIVEThis study aims to delineate the pathogenic pathway linking gut microbiota to peritoneal neutrophil activation and the development of endometriosis.DESIGNWe combined single-cell RNA sequencing of clinical peritoneal fluid immune cells with functional validation in heterologous and homologous mice models. We further adopted microbial source-tracking analysis of patient cohorts and interventional strategies, including faecal microbiota transplantation (FMT) and administration of green fluorescent protein (GFP)-tagged Pseudomonas aeruginosa.RESULTSWe identified a unique membrane metalloendopeptidase (MME) positive neutrophil subset (Neu_MME) that is expanded in endometriosis and primed for NETs formation (NETosis). These Neu_MME released NETs in response to bacterial lipopolysaccharides (LPS), which directly captured endometrial cells and enhanced their proliferation and migration, driving lesion development. Accordingly, inhibiting NETosis or degrading NETs significantly suppressed endometriosis in mice. Furthermore, FMT from patients with endometriosis to mice disrupted the intestinal barrier, promoting the translocation of gut microbiota, particularly Pseudomonas, into the peritoneal cavity and the lesions. This translocated Pseudomonas was identified as a key driver of LPS-induced NETosis and disease progression.CONCLUSIONOur findings define a gut-peritoneum axis in endometriosis, where gut-derived Pseudomonas triggers NETosis in peritoneal Neu_MME to promote disease, suggesting that targeting this bacterium or NETosis represents a viable therapeutic strategy.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"1 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145644983","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}
Pub Date : 2025-11-28DOI: 10.1136/gutjnl-2025-337415
Sunil Gupta,Nicholas G Burgess,Michael J Bourke
{"title":"Response to: 'Rectal versus colonic submucosal cancer rates and procedural outcomes in large non-pedunculated polyps: French ESD registry data' by Van der Voort et al.","authors":"Sunil Gupta,Nicholas G Burgess,Michael J Bourke","doi":"10.1136/gutjnl-2025-337415","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-337415","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":"2 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145613348","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}
Pub Date : 2025-11-28DOI: 10.1136/gutjnl-2025-337129
Robert Thimme,Maike Hofmann,Antonio Bertoletti,Nina Le Bert
Chronic HBV infection remains a major global health burden, with current antiviral therapies effectively suppressing viral replication but rarely achieving functional cure. Adaptive immunity is central to viral clearance but is profoundly impaired during chronic infection. Inducing and enhancing adaptive immunity through therapeutic vaccines, immune checkpoint inhibitors or T cell-based therapies represents a promising approach for HBV cure strategies. However, recent preclinical and clinical studies have demonstrated only limited efficacy, underscoring major immunological challenges. In this review, we summarise current knowledge of the correlates of viral clearance and persistence, discuss key unresolved questions and outline future research directions needed to advance immune-based HBV cure strategies.
{"title":"Decoding HBV-specific adaptive immunity: from natural clearance to cure.","authors":"Robert Thimme,Maike Hofmann,Antonio Bertoletti,Nina Le Bert","doi":"10.1136/gutjnl-2025-337129","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-337129","url":null,"abstract":"Chronic HBV infection remains a major global health burden, with current antiviral therapies effectively suppressing viral replication but rarely achieving functional cure. Adaptive immunity is central to viral clearance but is profoundly impaired during chronic infection. Inducing and enhancing adaptive immunity through therapeutic vaccines, immune checkpoint inhibitors or T cell-based therapies represents a promising approach for HBV cure strategies. However, recent preclinical and clinical studies have demonstrated only limited efficacy, underscoring major immunological challenges. In this review, we summarise current knowledge of the correlates of viral clearance and persistence, discuss key unresolved questions and outline future research directions needed to advance immune-based HBV cure strategies.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"71 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145613354","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}
BACKGROUNDDepending on the colorectal cancer (CRC) screening programme, a colonoscopy should be performed within 1-3 months after a positive faecal immunochemical test (FIT) result. However, such short timescales may be difficult to meet and seem trivial when most CRCs take years to develop.OBJECTIVETo assess the impact of time to colonoscopy on CRC outcomes.DESIGNThis French nationwide retrospective cohort study included individuals with a positive FIT result between 2016 and 2019 and a subsequent colonoscopy performed within 24 months. The risks of CRC, advanced-stage CRC and advanced adenoma (AA) according to time interval to colonoscopy were assessed and evaluated on individual and socio-geographic characteristics.RESULTSOverall, 374 113 FIT-positive individuals underwent post-FIT colonoscopy (86.6% compliance rate), with 21 616 CRCs and 122 359 AAs diagnosed. Compared with the 2-3 months interval class, no increased risk of CRC, advanced-stage CRC or AA was observed after 3 months up to 24 months, with adjusted odds ratio after 12 months at 0.93 (0.95 CI 0.83 to 1.03), 1.04 (0.85 to 1.25) and 0.88 (0.82 to 0.93), respectively. Individuals with high faecal haemoglobin concentrations (f-Hb ≥200 µg/g) were respectively eight, eleven and two times more likely to have a CRC, an advanced-stage CRC or an AA as compared with the 30-40 µg/g class.CONCLUSIONNo increased risk of CRC, advanced-stage CRC or AA was observed up to 24 months. Our findings suggest that ensuring colonoscopy compliance after a positive FIT may take precedence over rigid adherence to interval. The higher the f-Hb, the sooner the colonoscopy should be performed.
{"title":"Does a long time to colonoscopy after a positive faecal immunochemical test result have a deleterious impact on colorectal cancer outcomes? A nationwide cohort study.","authors":"Adrien Grancher,Bernard Denis,Julie Plaine,Somany Vidal-Sengchanh,Marie-Christine Quertier,Cécile Quintin,Lydia Guittet","doi":"10.1136/gutjnl-2025-336036","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-336036","url":null,"abstract":"BACKGROUNDDepending on the colorectal cancer (CRC) screening programme, a colonoscopy should be performed within 1-3 months after a positive faecal immunochemical test (FIT) result. However, such short timescales may be difficult to meet and seem trivial when most CRCs take years to develop.OBJECTIVETo assess the impact of time to colonoscopy on CRC outcomes.DESIGNThis French nationwide retrospective cohort study included individuals with a positive FIT result between 2016 and 2019 and a subsequent colonoscopy performed within 24 months. The risks of CRC, advanced-stage CRC and advanced adenoma (AA) according to time interval to colonoscopy were assessed and evaluated on individual and socio-geographic characteristics.RESULTSOverall, 374 113 FIT-positive individuals underwent post-FIT colonoscopy (86.6% compliance rate), with 21 616 CRCs and 122 359 AAs diagnosed. Compared with the 2-3 months interval class, no increased risk of CRC, advanced-stage CRC or AA was observed after 3 months up to 24 months, with adjusted odds ratio after 12 months at 0.93 (0.95 CI 0.83 to 1.03), 1.04 (0.85 to 1.25) and 0.88 (0.82 to 0.93), respectively. Individuals with high faecal haemoglobin concentrations (f-Hb ≥200 µg/g) were respectively eight, eleven and two times more likely to have a CRC, an advanced-stage CRC or an AA as compared with the 30-40 µg/g class.CONCLUSIONNo increased risk of CRC, advanced-stage CRC or AA was observed up to 24 months. Our findings suggest that ensuring colonoscopy compliance after a positive FIT may take precedence over rigid adherence to interval. The higher the f-Hb, the sooner the colonoscopy should be performed.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"71 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145613228","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}
BACKGROUNDThe prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly increasing with high risk to develop cirrhosis, hepatocellular carcinoma (HCC) and other end-stage liver diseases. However, only two drugs, resmetirom and semaglutide, have been approved by the US food and drug administration (FDA) for the treatment of MASLD, with relative low efficient and obvious side effects. Nanomaterials emerged with constantly growing availability of disease therapy benefiting from their well biocompatibility and appropriate properties.OBJECTIVEThe aim of our present study is to identify and fabricate new nanoparticles with high clinical translational potential for MASLD therapy.DESIGNWe systematically screened biocompatible nanoparticles for anti-MASLD capacities in vitro by evaluating their regulatory effects on perilipin-2 (PLIN2), the key molecule in lipid droplet (LD) formation and stability. The exact effects and molecular mechanisms of the identified nanoparticle on MASLD were explored in both cellular and animal models.RESULTSWe identified a carboxyl fullerene derivative, named four malonate groups-substituted C70 fullerene (QF70), as the most potent candidate for MASLD therapy. Notably, QF70 could facilitate lysosomal degradation of PLIN2. More importantly, oral administration of QF70 robustly blocked both diet-induced and leptin deficiency-induced MASLD development with significant improvement in obesity and insulin resistance. We further validated the clinical application potential of QF70 in MASLD-related metabolic disorders in a non-primate model.CONCLUSIONSThis study provides proof-of-concept supporting a nanoparticle-based agent as a LD homeostasis-targeted therapeutic to treat MASLD and related metabolic diseases.
{"title":"Discovery of a carboxyl fullerene derivative as a new lipid droplet regulator inhibiting MASLD.","authors":"Toujun Zou,Juan Wan,Rufang Liao,Lan Bai,Xinyan Li,Xu Cheng,Junjie Zhou,Qinchao Tang,Yufeng Zhang,Chong Zhao,Weiyi Qu,Jinjie Yang,Xiang Zhang,Tian Tian,Xinxin Yao,Zhiwei Cai,Song Tian,Jingwei Jiang,Yufeng Hu,Hailong Yang,Ejuan Zhang,Yun Chen,Bingqiong Yu,Jingjing Cai,Haibo Xu,Chunru Wang,Xiao-Jing Zhang,Zhi-Gang She,Hongliang Li","doi":"10.1136/gutjnl-2025-336268","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-336268","url":null,"abstract":"BACKGROUNDThe prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly increasing with high risk to develop cirrhosis, hepatocellular carcinoma (HCC) and other end-stage liver diseases. However, only two drugs, resmetirom and semaglutide, have been approved by the US food and drug administration (FDA) for the treatment of MASLD, with relative low efficient and obvious side effects. Nanomaterials emerged with constantly growing availability of disease therapy benefiting from their well biocompatibility and appropriate properties.OBJECTIVEThe aim of our present study is to identify and fabricate new nanoparticles with high clinical translational potential for MASLD therapy.DESIGNWe systematically screened biocompatible nanoparticles for anti-MASLD capacities in vitro by evaluating their regulatory effects on perilipin-2 (PLIN2), the key molecule in lipid droplet (LD) formation and stability. The exact effects and molecular mechanisms of the identified nanoparticle on MASLD were explored in both cellular and animal models.RESULTSWe identified a carboxyl fullerene derivative, named four malonate groups-substituted C70 fullerene (QF70), as the most potent candidate for MASLD therapy. Notably, QF70 could facilitate lysosomal degradation of PLIN2. More importantly, oral administration of QF70 robustly blocked both diet-induced and leptin deficiency-induced MASLD development with significant improvement in obesity and insulin resistance. We further validated the clinical application potential of QF70 in MASLD-related metabolic disorders in a non-primate model.CONCLUSIONSThis study provides proof-of-concept supporting a nanoparticle-based agent as a LD homeostasis-targeted therapeutic to treat MASLD and related metabolic diseases.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"55 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145613229","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}
Pub Date : 2025-11-26DOI: 10.1136/gutjnl-2025-336532
Crystal S Liu,Blair Merrick,Zahra S Taboun,Benjamin H Mullish,Simon D Goldenberg,Elisabeth M Terveer,Serena Porcari,Richard S Bradbury,Gianluca Ianiro,Siew C Ng, ,Dina Kao,Ed Kuijper
Rigorous donor screening is fundamental for the safe and effective delivery of faecal microbiota transplantion (FMT) services, whether in the treatment of Clostridioides difficile infection or within microbiome intervention clinical trials. Donor screening is of paramount importance given the potential risk of pathogen transmission-a feared complication. While rare in practice, documented cases of FMT-associated infections have resulted in significant morbidity and even mortality. Despite the importance of screening, evidence-based approaches to developing donor-screening protocols are lacking. Inadequate screening for transmissible pathogens may lead to infections in recipients, while overly cautious screening for pathogens with negligible transmission potential could strain healthcare resources and unnecessarily exclude donors, who are already in limited supply. This review aimed to evaluate the evidence underpinning current FMT donor screening protocols. We began by comparing protocols from major FMT guidelines and manufacturers, highlighting their differences in lists of screened pathogens, laboratory assays and clinical characteristics used for donor selection. We critically appraised the existing literature on transmission dynamics for pathogens. These findings were incorporated into a Delphi process with an expert panel group to develop a rational and streamlined screening approach. We further emphasised the importance of maintaining transparency with regard to donor recruitment, screening, monitoring and traceback record keeping. Finally, we explored future directions in donor screening, including approaches to monitoring emerging pathogens and the potential for integration of new technologies, such as metagenomic assays, to enhance and refine donor selection.
{"title":"Towards optimising and standardising donor screening for faecal microbiota transplantion.","authors":"Crystal S Liu,Blair Merrick,Zahra S Taboun,Benjamin H Mullish,Simon D Goldenberg,Elisabeth M Terveer,Serena Porcari,Richard S Bradbury,Gianluca Ianiro,Siew C Ng, ,Dina Kao,Ed Kuijper","doi":"10.1136/gutjnl-2025-336532","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-336532","url":null,"abstract":"Rigorous donor screening is fundamental for the safe and effective delivery of faecal microbiota transplantion (FMT) services, whether in the treatment of Clostridioides difficile infection or within microbiome intervention clinical trials. Donor screening is of paramount importance given the potential risk of pathogen transmission-a feared complication. While rare in practice, documented cases of FMT-associated infections have resulted in significant morbidity and even mortality. Despite the importance of screening, evidence-based approaches to developing donor-screening protocols are lacking. Inadequate screening for transmissible pathogens may lead to infections in recipients, while overly cautious screening for pathogens with negligible transmission potential could strain healthcare resources and unnecessarily exclude donors, who are already in limited supply. This review aimed to evaluate the evidence underpinning current FMT donor screening protocols. We began by comparing protocols from major FMT guidelines and manufacturers, highlighting their differences in lists of screened pathogens, laboratory assays and clinical characteristics used for donor selection. We critically appraised the existing literature on transmission dynamics for pathogens. These findings were incorporated into a Delphi process with an expert panel group to develop a rational and streamlined screening approach. We further emphasised the importance of maintaining transparency with regard to donor recruitment, screening, monitoring and traceback record keeping. Finally, we explored future directions in donor screening, including approaches to monitoring emerging pathogens and the potential for integration of new technologies, such as metagenomic assays, to enhance and refine donor selection.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"21 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145609912","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}
Pub Date : 2025-11-20DOI: 10.1136/gutjnl-2025-335163
Masaru Sasaki,Joshua X Wang,Ryugo Teranishi,Takefumi Itami,Yusen Zhou,Kanak V Kennedy,Ann Semeao,Satoshi Ishikawa,Takeo Hara,Emily A McMillan,Mark Mahon,Hailey Golden,Diya Dhakal,Alyssa Baccarella,Heidi Winters,Chizoba N Umeweni,Benjamin J Wilkins,Tatiana A Karakasheva,Kelly A Whelan,Sydney M Shaffer,Melanie A Ruffner,Amanda B Muir
BACKGROUNDEosinophilic oesophagitis (EoE) is a chronic allergic disease characterised by oesophageal epithelial remodelling, barrier dysfunction and inflammation. The transcription factor forkhead box M1 (FOXM1) has been shown to be a key regulator of epithelial proliferation and inflammation in allergic asthma.OBJECTIVETo investigate the role of FOXM1 in epithelial disruption in EoE and to evaluate the therapeutic potential of FOXM1 inhibition.DESIGNFOXM1 expression was analysed in human oesophageal biopsies, patient-derived organoids and murine EoE models. Interleukin (IL)-13 stimulation was used to model EoE in vitro. Using FOXM1 inhibition via the small molecule Robert Costa Memorial drug-1 (RCM-1), small interfering RNA-mediated knockdown or FOXM1 overexpression, the roles of FOXM1 were assessed by histology, gene expression profiling, organoid formation rates, barrier integrity and proliferation assays. RNA sequencing and chromatin immunoprecipitation were performed to elucidate molecular mechanisms.RESULTSFOXM1 was significantly upregulated in patients with active EoE and localised to the basal epithelium. IL-13 increased FOXM1 expression in vitro. FOXM1 inhibition restored differentiation markers, reduced basal cell hyperplasia and proliferation, and improved barrier function. In a murine model, RCM-1 reduced epithelial changes and eosinophil infiltration. Conversely, FOXM1 overexpression promoted basal cell hyperplasia and proliferation. Mechanistically, FOXM1 directly regulated cell cycle gene, cyclin B1, which was upregulated in EoE and downregulated on FOXM1 inhibition. RCM-1 reduced phosphorylated STAT6 under IL-13 stimulation. FOXM1 expression was driven in part by an IL-13-PI3K/AKT axis.CONCLUSIONFOXM1 plays a pivotal role in epithelial disruption in EoE by driving proliferation and impairing differentiation. Targeting FOXM1 restores epithelial homeostasis, mitigates inflammation and offers a novel therapeutic approach for EoE.
嗜酸性食管炎（EoE）是一种以食管上皮重塑、屏障功能障碍和炎症为特征的慢性变应性疾病。转录因子叉头盒M1 （FOXM1）已被证明是过敏性哮喘中上皮细胞增殖和炎症的关键调节因子。目的探讨FOXM1在EoE上皮破坏中的作用，并评价FOXM1抑制的治疗潜力。在人食管活检、患者源性类器官和小鼠EoE模型中分析DESIGNFOXM1的表达。采用白细胞介素(IL)-13刺激法体外建立EoE模型。通过小分子Robert Costa Memorial药物-1 （RCM-1）、小干扰rna介导的敲低或FOXM1过表达来抑制FOXM1，通过组织学、基因表达谱、类器官形成率、屏障完整性和增殖试验来评估FOXM1的作用。通过RNA测序和染色质免疫沉淀来阐明其分子机制。结果foxm1在活动性EoE患者中表达显著上调，并定位于基底上皮。IL-13增加FOXM1在体外的表达。FOXM1抑制恢复分化标记，减少基底细胞增生和增殖，改善屏障功能。在小鼠模型中，RCM-1减少了上皮细胞的变化和嗜酸性粒细胞的浸润。相反，FOXM1过表达促进基底细胞增生和增殖。机制上，FOXM1直接调控细胞周期基因cyclin B1，该基因在EoE中上调，在FOXM1抑制中下调。在IL-13刺激下，RCM-1降低了磷酸化的STAT6。FOXM1的表达部分受IL-13-PI3K/AKT轴驱动。结论foxm1在EoE的上皮破坏中起关键作用，通过促进增殖和抑制分化。靶向FOXM1恢复上皮稳态，减轻炎症，为EoE提供了新的治疗方法。
{"title":"FOXM1 inhibition reduces IL-13-induced epithelial remodelling and inflammation in eosinophilic oesophagitis.","authors":"Masaru Sasaki,Joshua X Wang,Ryugo Teranishi,Takefumi Itami,Yusen Zhou,Kanak V Kennedy,Ann Semeao,Satoshi Ishikawa,Takeo Hara,Emily A McMillan,Mark Mahon,Hailey Golden,Diya Dhakal,Alyssa Baccarella,Heidi Winters,Chizoba N Umeweni,Benjamin J Wilkins,Tatiana A Karakasheva,Kelly A Whelan,Sydney M Shaffer,Melanie A Ruffner,Amanda B Muir","doi":"10.1136/gutjnl-2025-335163","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-335163","url":null,"abstract":"BACKGROUNDEosinophilic oesophagitis (EoE) is a chronic allergic disease characterised by oesophageal epithelial remodelling, barrier dysfunction and inflammation. The transcription factor forkhead box M1 (FOXM1) has been shown to be a key regulator of epithelial proliferation and inflammation in allergic asthma.OBJECTIVETo investigate the role of FOXM1 in epithelial disruption in EoE and to evaluate the therapeutic potential of FOXM1 inhibition.DESIGNFOXM1 expression was analysed in human oesophageal biopsies, patient-derived organoids and murine EoE models. Interleukin (IL)-13 stimulation was used to model EoE in vitro. Using FOXM1 inhibition via the small molecule Robert Costa Memorial drug-1 (RCM-1), small interfering RNA-mediated knockdown or FOXM1 overexpression, the roles of FOXM1 were assessed by histology, gene expression profiling, organoid formation rates, barrier integrity and proliferation assays. RNA sequencing and chromatin immunoprecipitation were performed to elucidate molecular mechanisms.RESULTSFOXM1 was significantly upregulated in patients with active EoE and localised to the basal epithelium. IL-13 increased FOXM1 expression in vitro. FOXM1 inhibition restored differentiation markers, reduced basal cell hyperplasia and proliferation, and improved barrier function. In a murine model, RCM-1 reduced epithelial changes and eosinophil infiltration. Conversely, FOXM1 overexpression promoted basal cell hyperplasia and proliferation. Mechanistically, FOXM1 directly regulated cell cycle gene, cyclin B1, which was upregulated in EoE and downregulated on FOXM1 inhibition. RCM-1 reduced phosphorylated STAT6 under IL-13 stimulation. FOXM1 expression was driven in part by an IL-13-PI3K/AKT axis.CONCLUSIONFOXM1 plays a pivotal role in epithelial disruption in EoE by driving proliferation and impairing differentiation. Targeting FOXM1 restores epithelial homeostasis, mitigates inflammation and offers a novel therapeutic approach for EoE.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"107 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145559034","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}
Pub Date : 2025-11-19DOI: 10.1136/gutjnl-2025-335134
Gaurav B Nigam, Kathryn Oakland, Sarah Hearnshaw, John Grasnt-Casey, Paul Davies, Paula Dhiman, Shane W Goodwin, Bhaskar Kumar, Elizabeth Ratcliffe, Joanna A Leithead, Raman Uberoi, Lise Estcourt, Vipul Jairath, Simon P L Travis, Mike F Murphy, Adrian Stanley, Andrew Douds
Background Acute upper gastrointestinal bleeding (AUGIB) is a common medical emergency with evolving demographics and management strategies, particularly in medical/endoscopic therapy and transfusion strategies. Objective To provide key data of the most recent 2022 UK audit and compare it with the preceding audit in 2007. Design Prospective multicentre audit conducted from 3 May to 2 July 2022, including adults (≥16 years) with AUGIB across 147 UK hospitals (response rate 86% vs 84% in 2007). AUGIB was defined by clinical symptoms (haematemesis, haematochezia, coffee ground vomiting or melaena confirmed by medical personnel). Patients were followed until discharge, death or 28 days, with re-admissions during the study period counted as new episodes. Results Among 5141 patients (59% male; median age 69), 15% had cirrhosis, 19% reported excess alcohol use, 7% used non-steroidal anti-inflammatory drugs (NSAIDs) and 46% were on antithrombotics. Most (77%) were new admissions, who were younger with fewer comorbidities, while the remainder bled during hospitalisation. Peptic ulcer disease accounted for 32% of cases, varices for 10% and no abnormality was found in 33%. Pre-endoscopic risk stratification was not performed in 42%. Compared with 2007, patients in 2022 had higher comorbidity (67% vs 50%), more cirrhosis (15% vs 9%), greater anticoagulant use (31% vs 13%) and higher transfusion rates (50% vs 43%). In 2022, among early transfusions (pre-endoscopy or within first 24 hrs; 38%), 43% were given at haemoglobin (Hb)>70 g/L, with 24% classified as inappropriate due to haemodynamic stability. A signal of harm was observed: while inappropriate transfusion was not associated with rebleeding at either 70 or 80 g/L, at 80 g/L it was linked to higher adjusted mortality (adjusted OR (aOR) 1.60, 95% CI 1.00 to 2.56). Inpatient endoscopy was more common (83% vs 74%), though endotherapy use remained modest (27% vs 23%). Salvage therapy rates were unchanged (3.3% vs 3.1%) but shifted from surgery to interventional radiology. Outcomes improved, with lower rebleeding (9.7% vs 13.3%), reduced in-hospital mortality (8.8% vs 10.0%) and shorter median stay (5 vs 6 days). In multivariate analysis, mortality was independently predicted by older age (≥80 years: aOR 2.32, 95% CI 1.64 to 3.30), shock (aOR 2.22, 95% CI 1.53 to 3.17) and comorbidity, while lower Hb at presentation increased risk (≤70 g/L: aOR 1.56, 95% CI 1.15 to 2.11). Anticoagulant use was associated with increased mortality (aOR 1.43, 95% CI 1.11 to 1.85), whereas NSAID use (aOR 0.49, 95% CI 0.25 to 0.96) and antiplatelet use (aOR 0.68, 95% CI 0.54 to 0.87) were associated with lower mortality. Conclusions Despite a higher-risk case mix and incomplete adherence to guidelines (notably in transfusion thresholds and risk stratification), outcomes in AUGIB have improved. The observation of increased mortality with liberal transfusion above 80 g/L in stable patients reinforces the importance of restrictive t
背景急性上消化道出血（AUGIB）是一种常见的医疗紧急情况，其人口统计学和管理策略不断发展，特别是在医疗/内窥镜治疗和输血策略方面。目的提供最新的2022年英国审计的关键数据，并将其与2007年的审计进行比较。设计前瞻性多中心审计于2022年5月3日至7月2日进行，包括147家英国医院的AUGIB成人（≥16岁）（响应率为86%，而2007年为84%）。AUGIB的定义是临床症状（呕血、赤衣、咖啡渣呕吐或医务人员确认的黑黑）。随访患者至出院、死亡或28天，研究期间再次入院计算为新发作。结果在5141例患者中（59%为男性，中位年龄69岁），15%患有肝硬化，19%报告过量饮酒，7%使用非甾体抗炎药（NSAIDs）， 46%使用抗血栓药物。大多数（77%）是新入院的患者，他们更年轻，合并症较少，而其余患者在住院期间出血。消化性溃疡占32%，静脉曲张占10%，未发现异常的占33%。42%的患者未进行内镜前风险分层。与2007年相比，2022年的患者有更高的合并症（67%对50%），更多的肝硬化（15%对9%），更多的抗凝血剂使用（31%对13%）和更高的输血率（50%对43%）。2022年，在早期输血（内镜检查前或前24小时内；38%）中，43%的输血量为血红蛋白（Hb） bbb70 g/L，其中24%因血流动力学稳定性被归类为不合适。观察到一个危害信号：虽然不适当的输血在70或80 g/L时与再出血无关，但在80 g/L时与较高的调整死亡率相关（调整or (aOR) 1.60, 95% CI 1.00至2.56）。住院患者内窥镜检查更常见（83%对74%），尽管内窥镜治疗的使用仍然适度（27%对23%）。挽救治疗率不变（3.3% vs 3.1%），但从手术转向介入放射治疗。结果得到改善，再出血率降低（9.7%对13.3%），住院死亡率降低（8.8%对10.0%），中位住院时间缩短（5天对6天）。在多变量分析中，死亡率由年龄较大（≥80岁：aOR 2.32, 95% CI 1.64至3.30）、休克（aOR 2.22, 95% CI 1.53至3.17）和合病独立预测，而出现时较低的Hb增加了风险（≤70 g/L: aOR 1.56, 95% CI 1.15至2.11）。抗凝剂的使用与死亡率增加相关（aOR 1.43, 95% CI 1.11至1.85），而非甾体抗炎药的使用（aOR 0.49, 95% CI 0.25至0.96）和抗血小板的使用（aOR 0.68, 95% CI 0.54至0.87）与较低的死亡率相关。结论：尽管高危病例组合和不完全遵守指南（特别是在输血阈值和风险分层方面），但AUGIB的结果有所改善。在病情稳定的病人中，自由输血超过80 g/L死亡率增加的观察结果加强了限制性输血实践的重要性。质量改进计划侧重于风险分层、内窥镜培训和多学科护理，可以进一步提高英国和国际上的结果。如有合理要求，可提供资料。
{"title":"Acute upper gastrointestinal bleeding in the UK: 2022 audit update","authors":"Gaurav B Nigam, Kathryn Oakland, Sarah Hearnshaw, John Grasnt-Casey, Paul Davies, Paula Dhiman, Shane W Goodwin, Bhaskar Kumar, Elizabeth Ratcliffe, Joanna A Leithead, Raman Uberoi, Lise Estcourt, Vipul Jairath, Simon P L Travis, Mike F Murphy, Adrian Stanley, Andrew Douds","doi":"10.1136/gutjnl-2025-335134","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-335134","url":null,"abstract":"Background Acute upper gastrointestinal bleeding (AUGIB) is a common medical emergency with evolving demographics and management strategies, particularly in medical/endoscopic therapy and transfusion strategies. Objective To provide key data of the most recent 2022 UK audit and compare it with the preceding audit in 2007. Design Prospective multicentre audit conducted from 3 May to 2 July 2022, including adults (≥16 years) with AUGIB across 147 UK hospitals (response rate 86% vs 84% in 2007). AUGIB was defined by clinical symptoms (haematemesis, haematochezia, coffee ground vomiting or melaena confirmed by medical personnel). Patients were followed until discharge, death or 28 days, with re-admissions during the study period counted as new episodes. Results Among 5141 patients (59% male; median age 69), 15% had cirrhosis, 19% reported excess alcohol use, 7% used non-steroidal anti-inflammatory drugs (NSAIDs) and 46% were on antithrombotics. Most (77%) were new admissions, who were younger with fewer comorbidities, while the remainder bled during hospitalisation. Peptic ulcer disease accounted for 32% of cases, varices for 10% and no abnormality was found in 33%. Pre-endoscopic risk stratification was not performed in 42%. Compared with 2007, patients in 2022 had higher comorbidity (67% vs 50%), more cirrhosis (15% vs 9%), greater anticoagulant use (31% vs 13%) and higher transfusion rates (50% vs 43%). In 2022, among early transfusions (pre-endoscopy or within first 24 hrs; 38%), 43% were given at haemoglobin (Hb)>70 g/L, with 24% classified as inappropriate due to haemodynamic stability. A signal of harm was observed: while inappropriate transfusion was not associated with rebleeding at either 70 or 80 g/L, at 80 g/L it was linked to higher adjusted mortality (adjusted OR (aOR) 1.60, 95% CI 1.00 to 2.56). Inpatient endoscopy was more common (83% vs 74%), though endotherapy use remained modest (27% vs 23%). Salvage therapy rates were unchanged (3.3% vs 3.1%) but shifted from surgery to interventional radiology. Outcomes improved, with lower rebleeding (9.7% vs 13.3%), reduced in-hospital mortality (8.8% vs 10.0%) and shorter median stay (5 vs 6 days). In multivariate analysis, mortality was independently predicted by older age (≥80 years: aOR 2.32, 95% CI 1.64 to 3.30), shock (aOR 2.22, 95% CI 1.53 to 3.17) and comorbidity, while lower Hb at presentation increased risk (≤70 g/L: aOR 1.56, 95% CI 1.15 to 2.11). Anticoagulant use was associated with increased mortality (aOR 1.43, 95% CI 1.11 to 1.85), whereas NSAID use (aOR 0.49, 95% CI 0.25 to 0.96) and antiplatelet use (aOR 0.68, 95% CI 0.54 to 0.87) were associated with lower mortality. Conclusions Despite a higher-risk case mix and incomplete adherence to guidelines (notably in transfusion thresholds and risk stratification), outcomes in AUGIB have improved. The observation of increased mortality with liberal transfusion above 80 g/L in stable patients reinforces the importance of restrictive t","PeriodicalId":12825,"journal":{"name":"Gut","volume":"19 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145553303","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}
Pub Date : 2025-11-18DOI: 10.1136/gutjnl-2025-335745
Lena Smets,Maria Francesca Viola,Markus Boesch,Jana Raman,Lukas Van Melkebeke,Max Nobis,Emilio Flint,Nika Pajk,Paola Brescia,Alessandra Silvestri,Rita Feio-Azevedo,Elodie Modave,Lander De Herdt,Annalisa Sanga,Oltin Tiberiu Pop,Olivier Govaere,Jef Verbeek,Alexandre Denadai-Souza,David Cassiman,Niels Vandamme,Bram Boeckx,Diether Lambrechts,Maria Rescigno,Christine Bernsmeier,Elizabeth A V Jones,Jan G Hengstler,Ahmed Ghallab,Colinda L G J Scheele,Frederik Nevens,Hannelie Korf,Guy Boeckxstaens,Schalk Willem Van der Merwe
BACKGROUNDBacterial translocation in cirrhosis can trigger infection and hepatic decompensation, leading to systemic inflammation, organ failure and increased mortality. These infections often originate from the gastrointestinal tract after bacteria breach the intestinal barrier and disseminate to systemic sites.OBJECTIVEIn this study, we explore the mechanisms underlying intestinal barrier dysfunction in cirrhosis using an experimental cirrhosis model and patient-derived intestinal biopsies.DESIGNWe developed a murine model of cirrhosis through chronic administration of carbon tetrachloride for up to 20 weeks. We investigated both the intestinal epithelial and vascular compartments and performed single-cell transcriptomic profiling of myeloid cells isolated from cirrhotic mice and from individuals with compensated and decompensated cirrhosis.RESULTSOur findings indicate that bacterial translocation in cirrhosis is the result of failure at multiple checkpoints, including aberrant epithelial cell death, vascular barrier damage and dysfunction of gut-vascular macrophages. In a preclinical model of cirrhosis, macrophages exhibited increased levels of monocyte-attracting chemokines, reduced bacterial clearance and impaired interactions with blood vessels. Importantly, depleting vascular-lining macrophages resulted in bacterial translocation to systemic sites, even in the absence of experimental liver disease. Transcriptional profiling of macrophages from duodenal biopsies of patients with cirrhosis indicated similar dysregulation of pathways supporting blood vessels and elevated expression of chemokines.CONCLUSIONSThis study emphasises the critical role of intestinal macrophages in preventing the dissemination of luminal bacteria and highlights the multifaceted breakdown of the intestinal barrier in cirrhosis and the importance of the gut-vascular barrier.
{"title":"Intestinal blood vessel-associated macrophages and gut-vascular barrier dysfunction in cirrhosis.","authors":"Lena Smets,Maria Francesca Viola,Markus Boesch,Jana Raman,Lukas Van Melkebeke,Max Nobis,Emilio Flint,Nika Pajk,Paola Brescia,Alessandra Silvestri,Rita Feio-Azevedo,Elodie Modave,Lander De Herdt,Annalisa Sanga,Oltin Tiberiu Pop,Olivier Govaere,Jef Verbeek,Alexandre Denadai-Souza,David Cassiman,Niels Vandamme,Bram Boeckx,Diether Lambrechts,Maria Rescigno,Christine Bernsmeier,Elizabeth A V Jones,Jan G Hengstler,Ahmed Ghallab,Colinda L G J Scheele,Frederik Nevens,Hannelie Korf,Guy Boeckxstaens,Schalk Willem Van der Merwe","doi":"10.1136/gutjnl-2025-335745","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-335745","url":null,"abstract":"BACKGROUNDBacterial translocation in cirrhosis can trigger infection and hepatic decompensation, leading to systemic inflammation, organ failure and increased mortality. These infections often originate from the gastrointestinal tract after bacteria breach the intestinal barrier and disseminate to systemic sites.OBJECTIVEIn this study, we explore the mechanisms underlying intestinal barrier dysfunction in cirrhosis using an experimental cirrhosis model and patient-derived intestinal biopsies.DESIGNWe developed a murine model of cirrhosis through chronic administration of carbon tetrachloride for up to 20 weeks. We investigated both the intestinal epithelial and vascular compartments and performed single-cell transcriptomic profiling of myeloid cells isolated from cirrhotic mice and from individuals with compensated and decompensated cirrhosis.RESULTSOur findings indicate that bacterial translocation in cirrhosis is the result of failure at multiple checkpoints, including aberrant epithelial cell death, vascular barrier damage and dysfunction of gut-vascular macrophages. In a preclinical model of cirrhosis, macrophages exhibited increased levels of monocyte-attracting chemokines, reduced bacterial clearance and impaired interactions with blood vessels. Importantly, depleting vascular-lining macrophages resulted in bacterial translocation to systemic sites, even in the absence of experimental liver disease. Transcriptional profiling of macrophages from duodenal biopsies of patients with cirrhosis indicated similar dysregulation of pathways supporting blood vessels and elevated expression of chemokines.CONCLUSIONSThis study emphasises the critical role of intestinal macrophages in preventing the dissemination of luminal bacteria and highlights the multifaceted breakdown of the intestinal barrier in cirrhosis and the importance of the gut-vascular barrier.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"7 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145545180","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}
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