Gut最新文献

{"title":"Time to focus on the real potential benefit of endobiliary radiofrequency ablation: stent patency in patients with cholangiocarcinoma.","authors":"Jeska A Fritzsche, Esmée Smit, Cyriel Y Ponsioen, Rogier P Voermans","doi":"10.1136/gutjnl-2023-331359","DOIUrl":"10.1136/gutjnl-2023-331359","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"e11"},"PeriodicalIF":23.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138290799","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":"Acute severe ulcerative colitis trials: the past, the present and the future.","authors":"Sailish Honap, Vipul Jairath, Bruce E Sands, Parambir S Dulai, Silvio Danese, Laurent Peyrin-Biroulet","doi":"10.1136/gutjnl-2024-332489","DOIUrl":"10.1136/gutjnl-2024-332489","url":null,"abstract":"<p><p>Acute severe ulcerative colitis (ASUC), characterised by bloody diarrhoea and systemic inflammation, is associated with a significant risk of colectomy and a small risk of mortality. The landmark trial of cortisone in 1955 was pivotal for two reasons: first, for establishing the efficacy of a drug that remains a first-line therapy today and, second, for producing the first set of disease severity criteria and clinical trial endpoints that shaped the subsequent ASUC trial landscape. Trials in the 1990s and at the turn of the millennium established the efficacy of infliximab and ciclosporin, but since then, there has been little progress in drug development for this high-risk population. This systematic review evaluates all interventional randomised controlled trials (RCTs) conducted in patients hospitalised with severe UC. It provides an overview of the efficacy of treatments from past to present and assesses the evolution of trial characteristics with respect to study populations, eligibility criteria and study designs over time. This review details ongoing RCTs in this field and provides a perspective on the challenges for future clinical trial programmes and how these can be overcome to help deliver novel ASUC therapies.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"1763-1773"},"PeriodicalIF":23.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247919","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":"Microbiota-induced S100A11-RAGE axis underlies immune evasion in right-sided colon adenomas and is a therapeutic target to boost anti-PD1 efficacy","authors":"Qiming Zhou, Linhan Lei, Junhong Cheng, Junyou Chen, Yuyang Du, Xuehua Zhang, Qing Li, Chuangen Li, Haijun Deng, Chi Chun Wong, Baoxiong Zhuang, Guoxin Li, Xiaowu Bai","doi":"10.1136/gutjnl-2024-332193","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-332193","url":null,"abstract":"Background Tumourigenesis in right-sided and left-sided colons demonstrated distinct features. Objective We aimed to characterise the differences between the left-sided and right-sided adenomas (ADs) representing the early stage of colonic tumourigenesis. Design Single-cell and spatial transcriptomic datasets were analysed to reveal alterations between right-sided and left-sided colon ADs. Cells, animal experiments and clinical specimens were used to verify the results. Results Single-cell analysis revealed that in right-sided ADs, there was a significant reduction of goblet cells, and these goblet cells were dysfunctional with attenuated mucin biosynthesis and defective antigen presentation. An impairment of the mucus barrier led to biofilm formation in crypts and subsequent bacteria invasion into right-sided ADs. The regions spatially surrounding the crypts with biofilm occupation underwent an inflammatory response by lipopolysaccharide (LPS) and an apoptosis process, as revealed by spatial transcriptomics. A distinct S100A11+ epithelial cell population in the right-sided ADs was identified, and its expression level was induced by bacterial LPS and peptidoglycan. S100A11 expression facilitated tumour growth in syngeneic immunocompetent mice with increased myeloid-derived suppressor cells (MDSC) but reduced cytotoxic CD8+ T cells. Targeting S100A11 with well-tolerated antagonists of its receptor for advanced glycation end product (RAGE) (Azeliragon) significantly impaired tumour growth and MDSC infiltration, thereby boosting the efficacy of anti-programmed cell death protein 1 therapy in colon cancer. Conclusion Our findings unravelled that dysfunctional goblet cells and consequential bacterial translocation activated the S100A11-RAGE axis in right-sided colon ADs, which recruits MDSCs to promote immune evasion. Targeting this axis by Azeliragon improves the efficacy of immunotherapy in colon cancer. Data are available on reasonable request.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"1 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160545","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":"Severe multiple therapy refractory colitis in a 46-year-old man.","authors":"Nora Carpay, Nanne K H de Boer, Andra Neefjes-Borst, Steven Bots","doi":"10.1136/gutjnl-2024-331934","DOIUrl":"10.1136/gutjnl-2024-331934","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"1617-1736"},"PeriodicalIF":23.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691659","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":"Efficacy of dupilumab in patients with prior exposure to topical steroids: facing second-line treatments for eosinophilic oesophagitis.","authors":"Pierfrancesco Visaggi, Nicola De Bortoli, Edoardo Savarino","doi":"10.1136/gutjnl-2023-331674","DOIUrl":"10.1136/gutjnl-2023-331674","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"e15"},"PeriodicalIF":23.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138884846","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":"Discomfort or pain: what's in a name?","authors":"Mark Edward McAlindon","doi":"10.1136/gutjnl-2023-331775","DOIUrl":"10.1136/gutjnl-2023-331775","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"e20"},"PeriodicalIF":23.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139424617","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":"Human milk oligosaccharide 2'-fucosyllactose protects against high-fat diet-induced obesity by changing intestinal mucus production, composition and degradation linked to changes in gut microbiota and faecal proteome profiles in mice.","authors":"Paola Paone, Dimitris Latousakis, Romano Terrasi, Didier Vertommen, Ching Jian, Valentina Borlandelli, Francesco Suriano, Malin E V Johansson, Anthony Puel, Caroline Bouzin, Nathalie M Delzenne, Anne Salonen, Nathalie Juge, Bogdan I Florea, Giulio G Muccioli, Herman Overkleeft, Matthias Van Hul, Patrice D Cani","doi":"10.1136/gutjnl-2023-330301","DOIUrl":"10.1136/gutjnl-2023-330301","url":null,"abstract":"<p><strong>Objective: </strong>To decipher the mechanisms by which the major human milk oligosaccharide (HMO), 2'-fucosyllactose (2'FL), can affect body weight and fat mass gain on high-fat diet (HFD) feeding in mice. We wanted to elucidate whether 2'FL metabolic effects are linked with changes in intestinal mucus production and secretion, mucin glycosylation and degradation, as well as with the modulation of the gut microbiota, faecal proteome and endocannabinoid (eCB) system.</p><p><strong>Results: </strong>2'FL supplementation reduced HFD-induced obesity and glucose intolerance. These effects were accompanied by several changes in the intestinal mucus layer, including mucus production and composition, and gene expression of secreted and transmembrane mucins, glycosyltransferases and genes involved in mucus secretion. In addition, 2'FL increased bacterial glycosyl hydrolases involved in mucin glycan degradation. These changes were linked to a significant increase and predominance of bacterial genera <i>Akkermansia</i> and <i>Bacteroides</i>, different faecal proteome profile (with an upregulation of proteins involved in carbon, amino acids and fat metabolism and a downregulation of proteins involved in protein digestion and absorption) and, finally, to changes in the eCB system. We also investigated faecal proteomes from lean and obese humans and found similar changes observed comparing lean and obese mice.</p><p><strong>Conclusion: </strong>Our results show that the HMO 2'FL influences host metabolism by modulating the mucus layer, gut microbiota and eCB system and propose the mucus layer as a new potential target for the prevention of obesity and related disorders.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"1632-1649"},"PeriodicalIF":23.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11420753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140915979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PARP-1 selectively impairs <i>KRAS</i>-driven phenotypic and molecular features in intrahepatic cholangiocarcinoma.","authors":"Friederike L Keggenhoff, Darko Castven, Diana Becker, Stojan Stojkovic, Jovana Castven, Carolin Zimpel, Beate K Straub, Tiemo Gerber, Harald Langer, Patricia Hähnel, Thomas Kindler, Jörg Fahrer, Colm J O'Rourke, Ursula Ehmer, Anna Saborowski, Lichun Ma, Xin Wei Wang, Timo Gaiser, Matthias S Matter, Christian Sina, Stefanie Derer, Ju-Seog Lee, Stephanie Roessler, Bernd Kaina, Jesper B Andersen, Peter R Galle, Jens U Marquardt","doi":"10.1136/gutjnl-2023-331237","DOIUrl":"10.1136/gutjnl-2023-331237","url":null,"abstract":"<p><strong>Objective: </strong>Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer with limited therapeutic options. <i>KRAS</i> mutations are among the most abundant genetic alterations in iCCA associated with poor clinical outcome and treatment response. Recent findings indicate that Poly(ADP-ribose)polymerase1 (PARP-1) is implicated in <i>KRAS</i>-driven cancers, but its exact role in cholangiocarcinogenesis remains undefined.</p><p><strong>Design: </strong><i>PARP-1</i> inhibition was performed in patient-derived and established iCCA cells using RNAi, CRISPR/Cas9 and pharmacological inhibition in <i>KRAS</i>-mutant, non-mutant cells. In addition, <i>Parp-1</i> knockout mice were combined with iCCA induction by hydrodynamic tail vein injection to evaluate an impact on phenotypic and molecular features of <i>Kras</i>-driven and <i>Kras</i>-wildtype iCCA. Clinical implications were confirmed in authentic human iCCA.</p><p><strong>Results: </strong>PARP-1 was significantly enhanced in <i>KRAS</i>-mutant human iCCA. PARP-1-based interventions preferentially impaired cell viability and tumourigenicity in human <i>KRAS</i>-mutant cell lines. Consistently, loss of <i>Parp-1</i> provoked distinct phenotype in <i>Kras/Tp53-</i>induced versus <i>Akt/Nicd-</i>induced iCCA and abolished <i>Kras</i>-dependent cholangiocarcinogenesis. Transcriptome analyses confirmed preferential impairment of DNA damage response pathways and replicative stress response mediated by CHK1. Consistently, inhibition of CHK1 effectively reversed PARP-1 mediated effects. Finally, <i>Parp-1</i> depletion induced molecular switch of <i>KRAS</i>-mutant iCCA recapitulating good prognostic human iCCA patients.</p><p><strong>Conclusion: </strong>Our findings identify the novel prognostic and therapeutic role of <i>PARP-1</i> in iCCA patients with activation of oncogenic <i>KRAS</i> signalling.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"1712-1724"},"PeriodicalIF":23.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11420749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated metagenomic and metabolomic analysis reveals distinctive stage-specific gut-microbiome-derived metabolites in intracranial aneurysms.","authors":"Haitao Sun, Kaijian Sun, Hao Tian, Xiheng Chen, Shixing Su, Yi Tu, Shilan Chen, Jiaxuan Wang, Meichang Peng, Meiqin Zeng, Xin Li, Yunhao Luo, Yugu Xie, Xin Feng, Zhuang Li, Xin Zhang, Xifeng Li, Yanchao Liu, Wei Ye, Zhengrui Chen, Zhaohua Zhu, Youxiang Li, Fangbo Xia, Hongwei Zhou, Chuanzhi Duan","doi":"10.1136/gutjnl-2024-332245","DOIUrl":"10.1136/gutjnl-2024-332245","url":null,"abstract":"<p><strong>Objective: </strong>Our study aimed to explore the influence of gut microbiota and their metabolites on intracranial aneurysms (IA) progression and pinpoint-related metabolic biomarkers derived from the gut microbiome.</p><p><strong>Design: </strong>We recruited 358 patients with unruptured IA (UIA) and 161 with ruptured IA (RIA) from two distinct geographical regions for conducting an integrated analysis of plasma metabolomics and faecal metagenomics. Machine learning algorithms were employed to develop a classifier model, subsequently validated in an independent cohort. Mouse models of IA were established to verify the potential role of the specific metabolite identified.</p><p><strong>Results: </strong>Distinct shifts in taxonomic and functional profiles of gut microbiota and their related metabolites were observed in different IA stages. Notably, tryptophan metabolites, particularly indoxyl sulfate (IS), were significantly higher in plasma of RIA. Meanwhile, upregulated tryptophanase expression and indole-producing microbiota were observed in gut microbiome of RIA. A model harnessing gut-microbiome-derived tryptophan metabolites demonstrated remarkable efficacy in distinguishing RIA from UIA patients in the validation cohort (AUC=0.97). Gut microbiota depletion by antibiotics decreased plasma IS concentration, reduced IA formation and rupture in mice, and downregulated matrix metalloproteinase-9 expression in aneurysmal walls with elastin degradation reduction. Supplement of IS reversed the effect of gut microbiota depletion.</p><p><strong>Conclusion: </strong>Our investigation highlights the potential of gut-microbiome-derived tryptophan metabolites as biomarkers for distinguishing RIA from UIA patients. The findings suggest a novel pathogenic role for gut-microbiome-derived IS in elastin degradation in the IA wall leading to the rupture of IA.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"1662-1674"},"PeriodicalIF":23.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497911","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":"Potential risk of porcine-derived pancreatic enzyme medication for the cross-species transmission of hepatitis E virus.","authors":"Nicola Frericks, Volker Kinast, Eike Steinmann","doi":"10.1136/gutjnl-2024-332577","DOIUrl":"10.1136/gutjnl-2024-332577","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"1599-1600"},"PeriodicalIF":23.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11420708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141184132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}