Gut最新文献

{"title":"Use of genetic analysis in adult cholestatic liver disease: lessons from progressive paediatric syndromes and cohort studies.","authors":"Roman Liebe, Frank Lammert, Hartmut H Schmidt, Marcin Krawczyk","doi":"10.1136/gutjnl-2025-337027","DOIUrl":"10.1136/gutjnl-2025-337027","url":null,"abstract":"<p><p>The increasing availability and decreasing costs of DNA sequencing have resulted in the re-grouping of rare, severe paediatric cases of progressive familial intrahepatic cholestasis (PFIC) with more frequent, later-onset cases of cholestasis (eg, intrahepatic cholestasis of pregnancy, benign recurrent intrahepatic cholestasis, low phospholipid-associated cholelithiasis) under the umbrella of genetic cholestasis. The common denominator is the presence of functional variants in the PFIC-associated genes, predominantly in <i>ABCB4</i>, <i>ABCB11</i> and <i>ATP8B1</i>, which cause PFIC types 1-3. Several other congenital diseases such as Alagille syndrome and alpha1-antitrypsin deficiency comprise cholestatic pruritus as frequent symptoms.With the availability of intestinal bile acid transporter inhibitors (IBATi) as new and efficacious therapeutics for pruritus, the most debilitating symptom of PFIC, it is essential to envision their usefulness for patients with later-onset cholestatic liver disease suffering from pruritus.In this review, we summarise published studies on the genetic makeup of patients with paediatric, juvenile and adult-onset cholestasis, and discuss their findings with respect to genotype-specific treatment with IBATi, ursodeoxycholic acid, or alternative drugs. The aim is to provide an overview of the genetic variants likely to be encountered in future sequencing investigations of patients with cholestatic liver diseases, and how to translate this genetic information into personalised treatment recommendations.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"2267-2277"},"PeriodicalIF":24.6,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148271327","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":"2078-2080"},"PeriodicalIF":24.6,"publicationDate":"2026-10-07","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":"Modulating the gut-reproductive tract axis: microbial influence on gynaecological cancer pathogenesis and treatment.","authors":"Xinyi Chen, Zhenqiang Zuo, Bingbing Xiao, Fangqing Zhao","doi":"10.1136/gutjnl-2025-337778","DOIUrl":"10.1136/gutjnl-2025-337778","url":null,"abstract":"<p><p>The gut microbiota plays a crucial role in regulating host immunity, metabolism and inflammation, with accumulating evidence linking its composition and function to the development and progression of cancers in the reproductive tract. Patients with ovarian, endometrial and cervical cancers exhibit distinct alterations in their gut microbiota, characterised by reduced microbial diversity and shifts towards taxa associated with dysbiosis and chronic inflammation. Mechanistically, gut-derived metabolites and microbial translocation appear to influence systemic immune responses and oestrogen metabolism, thereby fostering a tumour microenvironment conducive to cancer growth. Beyond its role in tumourigenesis, the gut microbiota also affects treatment outcomes. Dysbiosis can reduce sensitivity to chemotherapy and alter immunotherapy responses, while antibiotic use during cancer treatment has been linked to poorer prognosis. Clinically, these insights highlight emerging applications of microbiome modulation as biomarkers for patient stratification and as adjuvant approaches to enhance therapeutic efficacy in gynaecological oncology, underscoring the therapeutic potential of targeting the microbiota-through dietary interventions, probiotics or faecal microbiota transplantation-to improve cancer treatment outcomes. However, most of these applications remain investigational, and current evidence is limited by heterogeneity across study designs, patient cohorts and cancer subtypes. This review summarises current understanding of gut microbiota profiles in reproductive tract cancers, examines potential mechanisms by which the microbiota influences malignancy, discusses its impact on therapy response and explores its emerging role in precision oncology.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"2278-2291"},"PeriodicalIF":24.6,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156929","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":"Rapid muscle loss beyond the transplant waiting list: outcomes in immunotherapy-treated hepatocellular carcinoma","authors":"Najib Ben Khaled,Stefan Enssle,Jens Ricke,Julia Mayerle,Ignazio Piseddu","doi":"10.1136/gutjnl-2026-340713","DOIUrl":"https://doi.org/10.1136/gutjnl-2026-340713","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":"1 1","pages":"gutjnl-2026-340713"},"PeriodicalIF":24.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088898","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":"Zinc-dependent post-transcriptional control of hepatocyte fate in and regeneration of alcohol-associated liver disease.","authors":"Maite G Fernandez-Barrena, Craig J McClain","doi":"10.1136/gutjnl-2025-337941","DOIUrl":"10.1136/gutjnl-2025-337941","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"2085-2087"},"PeriodicalIF":24.6,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147305023","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":"Exploiting a purine imbalance to target <i>KRAS</i> mutant pancreatic adenocarcinomas.","authors":"Jorge Mota-Pino, Oscar Fernandez-Capetillo","doi":"10.1136/gutjnl-2025-337940","DOIUrl":"10.1136/gutjnl-2025-337940","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"2082-2083"},"PeriodicalIF":24.6,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118717","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":"Rise of prediagnostic molecular profiling in inflammatory bowel disease-can we close the door before the horse has bolted?","authors":"Nick Powell","doi":"10.1136/gutjnl-2025-336049","DOIUrl":"10.1136/gutjnl-2025-336049","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) is typically diagnosed after the onset of symptoms in the context of established, characteristic patterns of intestinal inflammation. However, there is now substantial evidence pointing to a prolonged, biologically active preclinical phase of disease. Analysis of archived biological samples from large-scale longitudinal cohort studies of healthy individuals, some of whom develop incident IBD, has identified different molecular features that can be detected many years before clinical presentation. These include increased titres of antimicrobial and autoreactive antibodies and perturbations in a complex network of circulating, immunologically active proteins. As well as affording 'diagnostic' opportunities to identify individuals destined to develop IBD, an integrated view of these multiple different molecular features enables speculation of potential proximal drivers of preclinical IBD. Consistently recognised associations include dysregulated mononuclear phagocyte-lymphocyte interactions, augmented chemotaxis, frequently relating to interferon-γ-driven chemokine programmes and evidence of early tissue injury, such as increased circulating extracellular matrix components and metalloproteinases. Increased levels of circulating antibacterial and antiviral antibody responses hint towards disordered host-microbe interactions as potential prime triggers for the transition between health and early disease, although it is possible that these serological responses are an epiphenomenon linked to early mucosal damage and microbial translocation. There is now a timely opportunity to develop these different molecular features into scalable and clinically tractable biomarker panels to detect preclinical disease and enable strategies to proactively intercept IBD before it even develops.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"2095-2101"},"PeriodicalIF":24.6,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146197617","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":"GI highlights from the literature","authors":"Philip J Smith","doi":"10.1136/gutjnl-2026-340753","DOIUrl":"https://doi.org/10.1136/gutjnl-2026-340753","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":"484 1","pages":"2292-2294"},"PeriodicalIF":24.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149092376","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":"Oleic acid promotes lung injury in hypertriglyceridaemia-associated acute pancreatitis via the PIEZO1/NR4A1/CPT1A axis impairing endothelial fatty acid oxidation.","authors":"Bingqing Bai, Weizhen Xiang, Xinwen Chen, Qiannan Chen, Xingyu Liu, Jiren Wang, Jun Li, Shaofei Wang, Jian Huang, Huizhong Gan, Luyao Zhang, Jiejie Zhu, Luyao Gao, Xiaoyuan Ge, Hua Wang, Xiaochang Liu, Qiao Mei","doi":"10.1136/gutjnl-2025-336441","DOIUrl":"10.1136/gutjnl-2025-336441","url":null,"abstract":"<p><strong>Background: </strong>Hypertriglyceridaemia-induced acute pancreatitis (HTG-AP) is frequently complicated by acute lung injury (ALI), which worsens prognosis. Oleic acid (OA), a major circulating free fatty acid, may play a key role, but the underlying mechanism remains unclear.</p><p><strong>Objective: </strong>To investigate the relationship between plasma OA and HTG-AP-associated ALI and to explore the mechanism by which OA disrupts endothelial barrier through PIEZO1-mediated impairment of fatty acid oxidation (FAO).</p><p><strong>Design: </strong>This study used clinical sample analysis, an HTG-AP mouse model and OA-stimulated human umbilical vein endothelial cells. The association between OA and ALI was evaluated, and PIEZO1 was identified as a potential OA target through calcium imaging, transcriptomics and the Human Protein Atlas. Genetic/pharmacological interventions, lipidomics, Seahorse assays and barrier function tests were used to characterise FAO impairment and barrier disruption. NR4A1 regulation of CPT1A was investigated through transcriptomic and ChIP assays. Finally, the pathway's function was validated in mice with endothelial-specific Piezo1 knockdown.</p><p><strong>Results: </strong>Clinical and animal data showed elevated plasma OA in HTG-AP, positively associated with ALI incidence and severity. Multidimensional data identified PIEZO1 as a key target mediating OA-induced endothelial dysfunction. Mechanistically, OA activated and upregulated PIEZO1, which suppressed NR4A1 expression, leading to downregulation of CPT1A and impaired FAO, ultimately disrupting the endothelial barrier. Endothelial-specific Piezo1 knockdown significantly alleviated HTG-AP-associated ALI in mice.</p><p><strong>Conclusion: </strong>OA promotes endothelial barrier dysfunction and exacerbates HTG-AP-associated ALI via the Piezo1/NR4A1/CPT1A axis by impairing FAO, offering a novel mechanistic insight and identifying potential therapeutic targets for HTG-AP-associated ALI.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"2199-2214"},"PeriodicalIF":24.6,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146226535","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>Roseburia inulinivorans</i> increases muscle strength.","authors":"Borja Martinez-Tellez, Milena Schönke, Artemiy Kovynev, Esther Garcia-Dominguez, Lourdes Ortiz-Alvarez, Aswin Verhoeven, Ranko Gacesa, Arnau Vich Vila, Quinten Raymond Ducarmon, David Jimenez-Pavon, Maria Del Carmen Gomez-Cabrera, Rinse K Weersma, Wiep-Klaas Smits, Martin Giera, Jonatan R Ruiz, Patrick Cn Rensen","doi":"10.1136/gutjnl-2025-336980","DOIUrl":"10.1136/gutjnl-2025-336980","url":null,"abstract":"<p><strong>Background: </strong>Gut bacteria have been implicated in a wide range of health conditions, yet their potential role in preventing and treating muscle-wasting disorders remains largely unexplored.</p><p><strong>Objective: </strong>We aimed to investigate whether specific gut microbial species are associated with muscle strength and to explore underlying mechanisms linking the gut microbiota to muscle health.</p><p><strong>Design: </strong>We conducted metagenomic analyses in cohorts of younger and older adults extensively phenotyped for muscle strength. Associations were tested between bacterial taxa and performance measures. Causality was assessed by oral supplementation of candidate species in antibiotic-treated mice. Metabolomic profiling and muscle phenotyping were performed to elucidate mechanisms.</p><p><strong>Results: </strong>The relative abundance of <i>Roseburia inulinivorans</i>, but not other <i>Roseburia</i> species, was positively associated with multiple strength measures including handgrip, leg press and bench press in humans. Supplementation of <i>R. inulinivorans</i> in mice significantly enhanced forelimb grip strength, whereas other <i>Roseburia</i> species had no effect. Metabolomic analyses revealed that <i>R. inulinivorans</i> reduced amino acid concentrations in the caecum and plasma, while activating the purine and pentose phosphate pathway in muscle. These changes coincided with increased muscle fibre size and a shift from type I to type II fibres. Accordingly, we observed that the relative abundance of <i>R. inulinivorans</i> is lower in older adults compared with young adults.</p><p><strong>Conclusion: </strong><i>R. inulinivorans</i> emerges as a species-specific modulator of muscle strength, linking gut microbiota to muscle metabolism and function. These findings support its potential as a probiotic candidate for nutraceutical interventions targeting age-related muscle-wasting diseases.</p><p><strong>Trial registration number: </strong>NCT02365129.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"2130-2142"},"PeriodicalIF":24.6,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147432602","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}