Gut最新文献

{"title":"Single-cell multimodal analysis reveals the dynamic immunopathogenesis of HBV-ACLF progression","authors":"Xi Liang, Jinjin Luo, Qian Zhou, Jiaojiao Xin, Jiaqi Li, Bo Peng, Meiqian Hu, Jing Jiang, Wei Qiang, Peng Li, Pengcheng Chen, Heng Yao, Huafen Zhang, Xingping Zhou, Jiaxian Chen, Wen Hu, Bingqi Li, Shiwen Ma, Xiao Wu, Xiao Li, Jing Zhang, Jinlin Cheng, Shourong Liu, Xiaoqing Fu, Yingyan Lu, Yingzi Ming, Xin Chen, Dongyan Shi, Jun Li","doi":"10.1136/gutjnl-2024-333308","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333308","url":null,"abstract":"Background Acute-on-chronic liver failure (ACLF) is a life-threatening syndrome involving dysfunction of multiple immune cell types. Objective This study aimed to comprehensively depict the dynamic trajectory of immune responses throughout the disease course of HBV-related ACLF (HBV-ACLF). Design Single-cell RNA sequencing and single-cell proteomics were performed on the peripheral blood mononuclear cells of 45 samples from 17 patients who were hospitalised (progressive/stable/recovering course of HBV-ACLF, 6/5/6) and 15 control subjects (liver cirrhosis, chronic hepatitis B and healthy controls, 5/5/5). Functional and mechanistic experiments were validated in vivo and in vitro. Results Single-cell multiomics analysis revealed specific changes in the peripheral immune response in ACLF. VCAN+CD14+-monocytes with activated interferon-stimulated genes and enhanced inflammatory functions, stimulated by HBV relapse and expanded in ACLF-1, fuelling early inflammatory storm. The subsequent apoptotic hepatocytes predominantly induce hyperinflammatory C-X-C motif chemokine receptor 2 (CXCR2)+-neutrophils and CD163+-monocytes, enriching in patients with progressive ACLF and serving as significant markers of disease deterioration. Cytotoxic T-cells were functionally impaired and significantly decreased in progressive patients. CXCR2+-neutrophils exhibited immunosuppressive activity and induced the exhaustion of cytotoxic T-cells. Pharmacological inhibition of CXCR2 significantly reduced neutrophils infiltration, restored cytotoxic T-cells and showed therapeutic effect in ACLF mice. Six immune cellular modules (CMs) were identified for patient stratification, with CM2 and CM6 showing strong predictive value for disease outcomes, and CM3 indicating a potential early therapeutic window. Conclusion Our longitudinal multiomics study revealed the dynamic evolution of the immune response in HBV-ACLF and characterised diverse immune patterns for the future precise management and therapeutic intervention. Data are available in a public, open access repository. Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. All data relevant to the study are included in the article or uploaded as supplementary information. The raw data for scRNA-seq and bulk RNA-seq used in this study have been deposited into the Genome Sequence Archive (<https://ngdc.cncb.ac.cn/gsa-human>, accession number: HRA007042, HRA007057 and HRA008336).","PeriodicalId":12825,"journal":{"name":"Gut","volume":"22 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899323","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":"Unravelling the heterogeneous HCC risk in indeterminate chronic hepatitis B.","authors":"Chien-Wei Su, Yuh-Jin Liang, Jaw-Ching Wu","doi":"10.1136/gutjnl-2025-335915","DOIUrl":"10.1136/gutjnl-2025-335915","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882795","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":"Real-world validation of a prognostic clinical index to predict steroid response in acute severe colitis: a single tertiary centre retrospective study.","authors":"Vincent Bouillon, Christophe De Terwangne, Claire Liefferinckx, Charlotte Minsart, Leila Amininejad, Denis Franchimont, Anneline Cremer","doi":"10.1136/gutjnl-2024-334413","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334413","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144872863","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":"ISG15 deficiency in hepatic stellate cells promotes TGFβ2-induced liver fibrosis by counteracting CREB1 ISGylation.","authors":"Yue Yuan, Jiaxuan Li, Dean Rao, Xun Lu, Min Chen, Xiaoping Chen, Xin Long, Bixiang Zhang, Huifang Liang, Qian Chen, Jianping Zhao","doi":"10.1136/gutjnl-2025-335327","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-335327","url":null,"abstract":"<p><strong>Background: </strong>Interferon (IFN)-stimulated gene 15 (ISG15) is a downstream molecule of the IFN pathways central to many cellular processes. ISG15 mainly exerts its function through a post-translational modification process known as ISGylation.</p><p><strong>Objective: </strong>In this study, the role of ISG15 in the activation of hepatic stellate cells (HSCs) and liver fibrosis was examined.</p><p><strong>Design: </strong>Liver fibrosis was established by carbon tetrachloride (CCl4), bile duct ligation (BDL) surgery and metabolic dysfunction-associated steatohepatitis (MASH) diet between HSC-specific deletion of ISG15 (ISG15cKO) and wild type mice. Using genetic strategies in vitro, the role of ISG15 in HSCs was established. Immunoprecipitation, luciferase reporter assays and chromatin-immunoprecipitation assays (ChIP) in combination with proteomics sequencing in HSCs were used to study the associated downstream mechanisms.</p><p><strong>Results: </strong>ISG15 was underexpressed in activated HSCs and fibrotic livers, showing an inverse correlation with α-smooth muscle actin in patients with liver fibrosis. ISG15cKO mice developed spontaneous hepatic fibrosis and showed exacerbated CCl4/BDL-induced fibrogenesis. In vitro, ISG15 modulated HSC activation, proliferation and excessive extracellular matrix production. ISG15 deficiency in HSCs promoted transforming growth factorβ2 (TGFβ2) transcription by enhancing phosphorylated cAMP responsive element binding protein 1 (CREB1) activity, thereby inducing CREB1 binding on TGFβ2 promoter regions to activate TGFβ2/SMAD2 signalling. ISGylation directly binds CREB1 on Lys-304 and Lys-305 to inhibit p-CREB1 activity. Overexpression of ISG15 in HSCs or pharmacological inhibition of CREB1 by 666-15 could abolish ISG15 deficiency-induced liver fibrosis in CCl4-treated mice.</p><p><strong>Conclusions: </strong>ISG15 regulated HSC activation and liver fibrosis in part via the CREB1/TGFβ2/SMAD2 regulatory pathway. Utilisation of ISG15-CREB1 signalling may be a potential therapeutic target for liver fibrosis.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144872862","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":"EUS-guided portal pressure measurement: how to make it more accurate?","authors":"Feng Zhang, Ying Lv, Yuzheng Zhuge, Lei Wang","doi":"10.1136/gutjnl-2025-336537","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-336537","url":null,"abstract":"We read the recently published article, ‘How accurate is EUS-guided direct portal vein pressure measurement? A comparison with intraoperative measurements’ with great interest. In this article,1 Singh and colleagues compared the endoscopic ultrasound (EUS)-portal vein pressure (PVP) technique with direct intraoperative PVP measurement using a novel compact manometer (CM) and a conventional pressure transducer (CPT) connected to an ECG monitor. They found a reasonable correlation for EUS-PVP (0.72) and good correlation intraoperatively (0.96). However, the Pearson coefficient of 0.72 indicates only moderate correlation, which raises several concerns. EUS-guided portal pressure gradient (EUS-PPG)/PVP measurement is a novel technique to evaluate portal hypertension. However, several critical issues have been raised in previous studies, including the impact of sedation, the safety in advanced cirrhosis and lack of data to predict prognosis.2 Furthermore, we identify additional important considerations that warrant discussion. In the present study, pretransplant EUS-PVP obtained by CM and CPT (27.12±6.2 …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"62 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840041","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":"Clinical results of an HBV-specific T-cell receptor-T-cell therapy (SCG101) in patients with HBV-related hepatocellular carcinoma treated in an investigator-initiated, interventional trial","authors":"Xiang'an Wu, Dongmei Quan, Wei Li, Karin Wisskirchen, Wei Wu, Yuhong Zhou, Yun-Peng Liu, Xueshuai Wan, Xiaorui Wang, Xuxu Zhang, Lu Yang, Mengyao Zheng, Ke Zhang, Ulrike Protzer, Shunda Du, Xiujuan Qu","doi":"10.1136/gutjnl-2025-335456","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-335456","url":null,"abstract":"Background SCG101 is an autologous T-cell therapy specifically targeting hepatitis B virus (HBV) using a natural, high-affinity T-cell receptor that is stably expressed. Objective We evaluated the safety, pharmacokinetics, pharmacodynamics and efficacy of SCG101 in patients with HBV-related hepatocellular carcinoma (HCC) in an investigator-initiated trial. Design Six human leucocyte antigen (HLA)-A*02:01-positive, serum hepatitis B surface antigen (HBsAg)-positive and hepatitis B e antigen-negative patients with advanced HBV-HCC, who had failed one to three prior systemic therapies, received SCG101 at doses of 5×107 or 1×108 TCR-T+ cells/kg three days after lymphodepletion. Results Within 1 week, all patients experienced a significant but transient alanine aminotransferase elevation paralleled by a 76±57 fold expansion of T cells detected in peripheral blood. No neurotoxicity, but a cytokine release syndrome reaching up to grade 3 was observed. However, these side effects were not dose-limiting and could be managed with corticosteroids, anti-interleukin-6 and/or vasopressor therapy. Indicating on-target activity of SCG101, serum HBsAg levels dropped by 1.96 (0.16–3.84) log10 within 2 weeks. According to modified Response Evaluation Criteria in Solid Tumours, three of the six patients achieved tumour shrinkage with a best percentage change in target lesion size of −19.5%, −74.6% and −100%. One showed complete remission of the target lesion, remaining progression-free for 27 months and one other achieved a durable (>6 months) remission. During follow-up (median 10.9 months), three patients died, and one was lost to follow-up. Conclusion As monotherapy for patients with HBV-HCC, SCG101 demonstrated pronounced antiviral and antitumour activities and a safety profile manageable with supportive care. SCG101’s T-cell expansion, serum HBsAg drop and tumour response collectively underscore on-target activity. Trial registration number [NCT05339321][1]. No data are available. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT05339321&atom=%2Fgutjnl%2Fearly%2F2025%2F08%2F12%2Fgutjnl-2025-335456.atom","PeriodicalId":12825,"journal":{"name":"Gut","volume":"6 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825202","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":"Global prevalence and gastrointestinal symptom burden of individuals with a history of cholecystectomy","authors":"Bo Konings, Lukas Michaja Balsiger, Johann Pall Hreinsson, Magnus Simrén, Shrikant I Bangdiwala, Ami D Sperber, Olafur S Palsson, Hans Törnblom, Jan Tack","doi":"10.1136/gutjnl-2024-334531","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334531","url":null,"abstract":"Background Cholecystectomy is commonly performed globally, and many patients with disorders of gut-brain interaction (DGBI) report that their symptoms have either preceded or developed following cholecystectomy. Objective To determine the global prevalence of a self-reported history of a cholecystectomy and investigate its association with fulfilling Rome IV diagnostic criteria for DGBI. Design First, we used population-based internet questionnaire data from the Rome Foundation Global Epidemiology Study (n=54 127) to calculate the cross-sectional prevalence of a self-reported history of cholecystectomy. Second, we compared the prevalence of meeting diagnostic criteria for DGBI by cholecystectomy, using logistic regression models to calculate ORs before and after adjusting (AOR) for potential confounders. Results We identified 2709 subjects with cholecystectomy, corresponding to a global prevalence of 5.0% (95% CI 4.8 to 5.2). Global differences followed an east to west gradient, ranging from 1.9% in Asia to 9.9% in North America. Cholecystectomy was associated with a higher prevalence of fulfilling symptom criteria for any DGBI (AOR 1.50, 56.2% with cholecystectomy vs 42.3% without cholecystectomy), with the highest AOR found for gastroduodenal (AOR 1.73; 19.9% vs 11.8%) and anorectal (AOR 1.71; 17.0% vs 8.4%) disorders, followed by oesophageal (AOR 1.47; 12.3% vs 6.6%) and bowel (AOR 1.38; 47.5% vs 35.4%) disorders. Conclusion Cholecystectomy is prevalent worldwide and varies across world regions. A history of this procedure is associated with a higher GI symptom burden, either due to new cholecystectomy-related symptomatic conditions, or persistent DGBI misattributed to biliary disease for which a cholecystectomy was erroneously performed. All data relevant to the study are included in the article or uploaded as supplementary information. The online supplement contains an extensive summary of all aggregated patient data used for the present study. For more information about the study database (Rome Foundation Global Epidemiology Study), we refer to the website of the Rome Foundation: <https://theromefoundation.org/research-institute-rome-foundation/rome-foundation-global-epidemiology-study/>. Access to the dataset is available according to the procedures outlined by the Rome Foundation Global Epidemiology Study group, upon approval of a submitted project proposal.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"107 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825204","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":"Mucosal transcriptomic landscape along the small and large intestines in individuals with and without type 2 diabetes","authors":"Hannah Gilliam-Vigh, Anne Marie Ellegaard, Martin Rønn Madsen, Asger Bach Lund, Benjamin Anderschou Holbech Jensen, Tina Vilsbøll, Kristoffer Rigbolt, Filip Krag Knop","doi":"10.1136/gutjnl-2024-334124","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334124","url":null,"abstract":"Background A detailed mapping of functional differences among intestinal regions in healthy individuals remains incomplete. Identifying regional alterations in individuals with type 2 diabetes (T2D) could enhance our understanding of disease-related intestinal changes. Objective To characterise the transcriptomic landscape along the entire intestinal tract in healthy individuals and those with T2D, and to create a publicly accessible database for future research. Design In this observational study, mucosal biopsies were obtained from 16 sites along the intestinal tract through anterograde and retrograde double-balloon endoscopy in 12 individuals with T2D and 12 normoglycaemic matched healthy individuals. Full transcriptomic analysis was performed. Genes with significantly different expressions between intestinal regions were analysed in terms of their biological mechanisms in healthy individuals, while regional expression profiles were compared between individuals with and without T2D. Results In healthy individuals, distinct gene clusters in the small and large intestines were associated with processes including immune response, mitochondrial activity and metabolism of organic substances. Individuals with T2D exhibited alterations in immune system activity and barrier permeability in the ileocaecal region and the large intestine. Conclusion Our study offers a detailed mapping of the transcriptomic landscape in the human intestinal tract, demonstrating regionalised gene expression profiles tied to critical biological processes. Notable alterations in immune system activity in the large intestine were observed in individuals with T2D. The publicly available database generated from this study (<https://rnaseq.gubra.dk/>) provides a valuable resource for exploring the mucosal transcriptome along the human intestinal tract. Trial registration number [NCT03044860][1] Data are available in a public, open access repository. Anonymous mRNA data are available indefinitely at <https://rnaseq.gubra.dk/>. The study protocol is included as a data supplement available with the online version of this article. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03044860&atom=%2Fgutjnl%2Fearly%2F2025%2F08%2F12%2Fgutjnl-2024-334124.atom","PeriodicalId":12825,"journal":{"name":"Gut","volume":"52 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825210","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":"Artificial intelligence-tailored bowel preparation reduces laxative burden and promotes sustainable endoscopy","authors":"Yang-Bor Lu, Si-Cun Lu, Yung-Ning Huang, Yu-Chieh Weng, Tung-Ying Chiang, Pei-Ting Cheng, Puo-Hsien Le, Cheng-Tang Chiu, Ankie T Cheung, Dorothy Chan, Raymond SY Tang, Xiao-Bing Cui, Hong-Zhi Xu, Shun-Tian Cai, Joseph JY Sung, Thomas YT Lam, Wei Gong","doi":"10.1136/gutjnl-2025-336200","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-336200","url":null,"abstract":"Artificial intelligence (AI) has proven effective in assessing bowel preparation adequacy, but its role in guiding personalised laxative dosing is untested. In this prospective, multicentre, endoscopist-masked randomised trial, 1650 participants were assigned to AI-assisted or conventional groups using self-evaluation (SE) by patients during a 3 L split-dose polyethylene glycol (PEG) regimen. The AI group used significantly less PEG (mean difference −496.1 mL; p<0.001) while maintaining similar bowel cleanliness, polyp detection rates (PDR) and withdrawal times. Right colon scores were slightly higher, with less nausea and bloating reported in the AI group. AI-assisted assessment (AIA) offers an effective personalised approach to colonoscopy and warrants evaluation with other regimens. Colonoscopy plays a vital role in early detection of colorectal cancer (CRC), with adequate bowel cleansing being essential for mucosal visualisation.1 Our team previously developed an AIA tool capable of real-time evaluation of rectal effluent images, providing instant feedback and matching conventional self-assessment in quality.2 Given growing interest in sustainable practices in gastrointestinal endoscopy, and the burden of high-volume purgative regimens, a more individualised, eco-friendly approach to bowel preparation is warranted. No randomised controlled trials (RCTs) have explored real-time, AI-guided titration of purgative volume. We hypothesised that AIA could efficiently reduce PEG intake to individuals’ needs while maintaining preparation adequacy. We conducted a prospective, endoscopist-blinded RCT at Xiamen Chang Gung Hospital and Shenzhen Hospital of Southern Medical University from July 2023 through July 2024 (ChiCTR2300067499). Eligible patients aged 18–75 scheduled for colonoscopy were randomised 1:1 to either a traditional SE groupor an AIA group. All patients received 1 L of PEG the night before colonoscopy. The SE group ingested a mandatory additional 2 L, guided by photographic comparisons of rectal effluent, while the AIA group ingested a titrated volume from the remaining 2 L, stopping once the AI system returned a ‘pass’ after defecation photo …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"40 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825203","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":"Intrahepatic donor microbiota-based metataxonomic signature detected in organ preservation solution enables prediction of short-term liver transplant outcomes","authors":"Fernando Lucas-Ruiz, Daniel Vidal-Correoso, Sandra V Mateo, María Magdalena de la Torre-Álamo, Marta Jover-Aguilar, Felipe Alconchel, Laura Martínez-Alarcón, Víctor Lopez-Lopez, Antonio Ríos-Zambudio, Pedro Cascales, Pablo Pelegrín, Jose Antonio Pons, Pablo Ramírez, Alberto Baroja-Mazo","doi":"10.1136/gutjnl-2025-335986","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-335986","url":null,"abstract":"Background Liver transplantation (LT) remains hampered by post-transplant complications. While gut microbiota dysbiosis has been linked to transplant outcomes, the role of the intrahepatic graft’s native microbiota remains unexplored. Objective To characterise the microbial profile detected in organ preservation solution (OPS) and determine whether specific microbial taxa are associated with short-term clinical outcomes, and to develop predictive models for risk stratification. Design We analysed the OPS microbiota-based metataxonomic signature from 110 LT donors (discovery cohort) and an independent validation cohort (n=29) using 16S rRNA sequencing. Microbial DNA signatures associated with clinical outcomes were identified through MaAsLin2-adjusted models, and relevant gene pathways were uncovered via data mining and enrichment analysis. Machine learning (ML) models were developed to predict outcomes based on microbial features, and host–microbiome interactions were validated through RNA sequencing (RNA-seq of matched liver biopsies). Results OPS-derived microbial DNA signature closely resembled liver/bile microbiomes (Proteobacteria-dominated). Specific genera (eg, Bacillus , Prevotella ) were differentially abundant in adverse outcomes (p<0.05): hyperabundant in non-survivors and hepatic artery thrombosis, hypoabundant in acute rejection (AR). Gene mining linked these taxa to immune/metabolic pathways relevant to LT outcomes. RNA-seq validated upregulation of chemokines (CCL/CXCL families) in liver grafts from non-surviving recipients. ML models accurately predicted global survival (area under the curve (AUC)=0.95) and AR (AUC=0.96) based on microbial features, with generalisability confirmed in the validation cohort (AUC=0.85–0.88). Conclusion Donor intrahepatic microbial DNA signature predicts LT outcomes via immune-metabolic modulation. While causality requires further study, these findings position the graft microbiome as a novel biomarker and potential therapeutic target, paving the way for microbiome-informed precision care in transplantation. Data are available in a public, open access repository. Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. Microbial and transcriptomic datasets generated in this study have been deposited in the NCBI public repositories under BioProject accession numbers PRJNA1262407 (16S rRNA gene sequencing of preservation fluid) and PRJNA1262719 (RNA-Seq of pre-transplant liver tissue), respectively. The rest of data, analytical methodologies and research materials that support the findings of this study are available from the corresponding author upon reasonable request.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"37 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825206","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}