Gut最新文献

{"title":"Correction: The Peptidoglycan Recognition Protein 1 confers immune evasive properties on pancreatic cancer stem cells","authors":"BMJ Publishing Group Ltd and British Society of Gastroenterology","doi":"10.1136/gutjnl-2023-330995corr1","DOIUrl":"https://doi.org/10.1136/gutjnl-2023-330995corr1","url":null,"abstract":"López-Gil JC, García-Silva S, Ruiz-Cañas L, et al. The Peptidoglycan Recognition Protein 1 confers immune evasive properties on pancreatic cancer stem …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"28 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142797047","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":"Redefining QUAIDE: paving the way for better AI in preclinical endoscopy","authors":"Hui Li, Tiantian Zhang, Qin Guo, Shufen Zhou, Chengshan Guo","doi":"10.1136/gutjnl-2024-334324","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334324","url":null,"abstract":"We read with great interest the recent article by Antonelli et al 1 on the quality assessment for artificial intelligence in digestive endoscopy (QUAIDE) framework, which enhances the quality and reproducibility of artificial intelligence (AI)-based gastrointestinal endoscopy research. While QUAIDE provides a solid foundation for pre-clinical research design, we see opportunities for further improvement in several key areas. First, preclinical endoscopy AI research often involves sensitive patient data, requiring strict adherence to data privacy and ethical standards.2 Currently, the QUAIDE framework does not adequately address data privacy protection, particularly in terms of anonymisation, de-identification, data-sharing agreements and informed consent. Including these standards is crucial for ensuring patient data safety, especially in multicentre collaborations, where varying anonymisation practices across centres increase the risk of data breaches.3 Establishing unified data management …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"24 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867313","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":"Is the biogeography of the mucosa-associated microbiota a key factor affecting primary sclerosing cholangitis disease course and treatment?","authors":"Yenkai Lim, Seungha Kang, Ayesha Shah, Gerald Holtmann, Mark Morrison","doi":"10.1136/gutjnl-2024-334069","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334069","url":null,"abstract":"We have read with interest the contribution by Bedke et al ,1 reporting changes in the stool microbiota associated with primary sclerosing cholangitis (PSC) in human and murine models of the disease. These changes coincide with an expansion of FoxP3+T reg cells, a response also linked with luminal butyrate concentrations and/or other goods and services arising from select commensal bacteria.2 Furthermore, the authors find patients with PSC with an associated IBD (PSC-IBD) as well as mice receiving faecal transfer from such patients experience a milder form of IBD, or attenuation of colitis, respectively. Their findings expand on those from Awoniyi et al , linking bile acid ecology and select stool bacteria deemed protective or pathogenic in a murine model of PSC, as well as an association of these microbial signatures with disease severity in patients with PSC.3 Attribution of the beneficial effects to the luminal/stool microbiota in both these studies was strengthened by their abrogation in mice following antibiotic administration. Interestingly, recent studies suggest that antibiotic treatment, and vancomycin administration in particular, can promote positive clinical benefits in both subjects with PSC and/or PSC-IBD regardless of age.4 Given the distinctive clinical features and epidemiology of PSC-IBD compared with IBD5 and the dichotomous impacts from antibiotics on disease course in different scenarios, …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"56 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867314","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":"Withdrawal of antitumour necrosis factor in inflammatory bowel disease patients in remission: a randomised placebo-controlled clinical trial of GETECCU","authors":"Javier P Gisbert, María G Donday, Sabino Riestra, Alfredo J Lucendo, José-Manuel Benítez, Mercè Navarro-Llavat, Jesús Barrio, Víctor J Morales-Alvarado, Montserrat Rivero, David Busquets, Eduardo Leo Carnerero, Olga Merino, Óscar Nantes Castillejo, Pablo Navarro, Manuel Van Domselaar, Ana Gutiérrez, Inmaculada Alonso-Abreu, Rafael Mejuto, Luis Fernández-Salazar, Marisa Iborra, María Dolores Martín-Arranz, Juan Ramón Pineda, Manuela Josefa Sampedro, Katja Serra Nilsson, Abdel Bouhmidi, Lissette Batista, Carmen Muñoz Villafranca, Iago Rodríguez-Lago, Daniel Ceballos, Iván Guerra, Miriam Mañosa, Ignacio Marín Jiménez, Emilio Torrella, Maribel Vera Mendoza, María José Casanova, Ruth de Francisco, Laura Arias-González, Sandra Marín Pedrosa, Orlando García-Bosch, Francisco Javier García-Alonso, Pedro Delgado-Guillena, María José García, Leyanira Torrealba, Andrea Núñez-Ortiz, Miren Vicuña Arregui, Marta Maia Bosca-Watts, Isabel Blázquez, Diana Acosta, Ana Garre, Montse Baldán, Concepción Martínez, Manuel Barreiro-de Acosta, Eugeni Domènech, Maria Esteve, Valle García-Sánchez, Pilar Nos, Julián Panés, María Chaparro","doi":"10.1136/gutjnl-2024-333385","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333385","url":null,"abstract":"Background and objectives Primary objectives: to compare the rates of sustained clinical remission at 12 months in patients treated with antitumour necrosis factor (anti-TNF) and immunomodulators who withdraw anti-TNF treatment versus those who maintain it. Secondary objectives: to evaluate the effect of anti-TNF withdrawal on relapse-free time, endoscopic and radiological activity, safety, quality of life and work productivity; and to identify predictive factors for relapse. Design Prospective, quadruple-blind, multicentre, randomised, controlled trial. Patients with ulcerative colitis or Crohn’s disease in clinical remission for >6 months and absence of severe endoscopic (and radiological in Crohn’s disease) lesions were randomised to maintain anti-TNF treatment (maintenance arm (MA)) or to withdraw it (withdrawal arm (WA)). All patients maintained immunomodulators. Patients were followed-up until month 12 or up to clinical relapse. Results One-hundred forty patients were randomised: 70 were allocated to the MA and 70 to the WA. The proportion of patients with sustained clinical remission at 12 months was similar in the MA and WA: 59/70 (84%), 95% CI=74% to 92% versus 53/70 (76%), 95% CI=64% to 85%. The proportion of patients with significant endoscopic lesions at the end of follow-up was 8.5% in the MA and 19% in the WA (p=0.1); a higher proportion of patients had faecal calprotectin >250 µg/g at the end of follow-up in the WA (p=0.01). The same percentage of patients in both groups had at least one adverse event (69%). The proportion of patients with serious adverse events was also similar in both groups (4% in MA vs 7% in WA). Conclusion Anti-TNF withdrawal in selected patients with IBD in clinical, endoscopic and radiological remission has no impact on sustained clinical remission at 1 year although objective markers of activity were higher in patients who withdrew treatment. Trial registration number <https://www.clinicaltrialsregister.eu/ctr-search/search?query=2015-001410-10> <https://clinicaltrials.gov/study/NCT02994836> Data are available upon reasonable request.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"111 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867316","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":"Early detection of colorectal cancer using aberrant circulating cell-free mitochondrial DNA fragmentomics","authors":"Siyuan Wang, Fan Peng, Miao Dang, Huanmin Jiao, Huanqin Zhang, Kaixiang Zhou, Wenjie Guo, Zhiyun Gong, Lin Guo, Renquan Lu, Deliang Li, Bingrong Liu, Xu Guo, Jinliang Xing, Yang Liu","doi":"10.1136/gutjnl-2024-333533","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333533","url":null,"abstract":"Background Early detection of colorectal cancer (CRC) is crucial for improving the survival rates of patients. Objective We aimed to develop a novel strategy for early CRC detection using the fragmentomic features of circulating cell-free mitochondrial DNA (ccf-mtDNA). Design Here, a total of 1147 participants, including 478 healthy controls (HCs), 112 patients with advanced adenomas (AAs) and 557 patients with CRC, were enrolled from five hospitals and plasma samples were collected for capture-based ccf-mtDNA sequencing. Results Our data analysis revealed significantly aberrant ccf-mtDNA fragmentomic features in patients with CRC and AA when compared with HCs. Then, a CRC detection (CD) model was constructed based on the fragmentomic features of ccf-mtDNA from 246 patients with CRC and 168 HC in the training cohort, showing area under the curve of 0.9863, sensitivity of 92.68% and specificity of 93.45%. Both internal and two external validation cohorts demonstrated the excellent capacity of CD model in distinguishing patients with early-stage CRC from HCs, greatly surpassing the performance of serum biomarkers. Furthermore, our CD model can also detect patients with AA with a sensitivity of 79.35% in AA cohort 1 and 85.00% in AA cohort 2. Conclusion In conclusion, based on aberrant ccf-mtDNA fragmentomic features, a novel and non-invasive approach was established for the detection of patients with early-stage CRC or AA, with high performance. Data are available upon reasonable request. The raw sequencing data underlying this article are available in BIG Data Center, Beijing Institute of Genomics (BIG) with access number PRJCA028508.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"30 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841617","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":"Faecalibacterium prausnitzii: one species with multiple potential implications in cancer research","authors":"Rodrigo Formiga, Harry Sokol","doi":"10.1136/gutjnl-2024-334338","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334338","url":null,"abstract":"The gut microbiota is pivotal for maintaining health through beneficial symbiotic interaction with the host supporting the homeostasis of the gastrointestinal tract but also of the majority of extraintestinal organs. Alterations in the gut microbiome have been linked to the pathogenesis of various diseases, including cancer, which remains a leading cause of mortality worldwide. The colonisation or overgrowth of certain bacterial species at the expense of others has been implicated in tumorigenesis. For instance, Helicobacter pylori infection is known to cause chronic inflammation and significantly increases the risk of developing gastric cancer, while Bacteroides fragilis and Fusobacterium nucleatum overgrowth have been associated with colorectal cancer (CRC). Consequently, several microbiota-based strategies have been developed to regulate cancer progression, enhance immune responses towards tumorous cells and improve the effectiveness of current anticancer therapies.1 Among the most abundant bacteria in the healthy human gut microbiota, Faecalibacterium prausnitzii , an anaerobic member of the Clostridium IV group, is significantly reduced in patients with different types of cancers.2 3 Several studies suggest that this species may have direct antitumour effects against breast cancer and CRC,3 4 or alternatively boost the response to chemotherapy, particularly the immune …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"11 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841284","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":"Early tumour necrosis factor antagonist treatment prevents perianal fistula development in children with Crohn's disease: post hoc analysis of the RISK study.","authors":"Jeremy Adler, Samir Gadepalli, Moshiur Rahman, Sandra Kim","doi":"10.1136/gutjnl-2024-333280","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333280","url":null,"abstract":"<p><strong>Background: </strong>One in three children with Crohn's disease develop perianal fistula complications (PFCs), among the most disturbing and difficult-to-treat disease-related complications. Retrospective evidence suggests PFCs may be preventable.</p><p><strong>Objective: </strong>We aimed to determine if early antitumour necrosis factor-alpha (anti-TNF⍺) therapy prevents PFC development in a well-characterised prospective cohort of paediatric patients with Crohn's disease who were free from PFC at enrolment.</p><p><strong>Design: </strong>RISK was a multicentre inception cohort of children newly diagnosed with Crohn's disease. We included all patients who had never experienced PFCs 30 days after study enrolment. We conducted nearest-neighbour propensity score-matched triad analyses. Matching was performed to balance patient characteristics across three mutually exclusive treatment groups based on therapy prior to either PFC development or the end of the observation period.</p><p><strong>Results: </strong>Among 873 patients without perianal fistula, 447 matched patients were included (149 per treatment group). The presence of non-penetrating perianal lesions (large skin tags, ulcers and/or fissures) was significantly associated with PFC development, with 4-fold greater odds of PFC (OR 4.08, 95% CI (95% CI) 1.70 to 9.78; p=0.0016). Early anti-TNF⍺ therapy was associated with an 82% decrease in the odds of PFC (OR 0.18, 95% CI 0.05 to 0.66; p=0.01). Among those with perianal lesions, anti-TNF⍺ therapy was associated with 94% reduced odds of PFC development (OR 0.055, 95% CI 0.006 to 0.50; p=0.010). No other treatment group was associated with reduced risk of PFC.</p><p><strong>Conclusion: </strong>Early anti-TNF therapy prevents perianal fistula development, especially among patients at increased risk.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":23.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817790","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":"Hepatic TM6SF2 activates antitumour immunity to suppress metabolic dysfunction-associated steatotic liver disease-related hepatocellular carcinoma and boosts immunotherapy.","authors":"Yating Zhang, Mingxu Xie, Jun Wen, Cong Liang, Qian Song, Weixin Liu, Yali Liu, Yang Song, Harry Cheuk Hay Lau, Alvin Ho-Kwan Cheung, Kwan Man, Jun Yu, Xiang Zhang","doi":"10.1136/gutjnl-2024-333154","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333154","url":null,"abstract":"<p><strong>Background: </strong>Transmembrane 6 superfamily member 2 (TM6SF2) has a protective role against metabolic dysfunction-associated steatotic liver disease (MASLD).</p><p><strong>Objective: </strong>We aim to investigate the mechanistic role and therapeutic potential of hepatic TM6SF2 in MASLD-related hepatocellular carcinoma (HCC).</p><p><strong>Design: </strong>Hepatocyte-specific <i>Tm6sf2</i> knockout (<i>Tm6sf2</i> ^∆hep) mice were fed with high-fat/high-cholesterol (HFHC) diet or diethylnitrosamine plus HFHC diet to induce MASLD-HCC. TM6SF2 function was also evaluated in orthotopic MASLD-HCC mice. Human MASLD-HCC specimens were included to evaluate clinical significance.</p><p><strong>Results: </strong>TM6SF2 was downregulated in tumours compared with adjacent normal tissues from MASLD-HCC patients. Hepatocyte-specific <i>Tm6sf2</i> knockout exacerbated tumour formation in mice with diet-induced or diet-induced and carcinogen-induced MASLD-HCC. The tumour-promoting effect of <i>Tm6sf2</i> knockout was verified in orthotopic MASLD-HCC mice, while mice bearing <i>Tm6sf2</i>-overexpressing tumours had opposite phenotypes. We observed the reduction of interferon-gamma (IFN-γ)⁺CD8⁺ T cells in the tumours of <i>Tm6sf2</i> ^∆hep mice and orthotopic <i>Tm6sf2</i> knockout mice, while the tumour-suppressive effect of <i>Tm6sf2</i> was abolished after depleting CD8⁺ T cells. The correlation between TM6SF2 and CD8⁺ T cells was confirmed in human MASLD-HCC tissues, inferring that TM6SF2 could promote antitumour immunity. Mechanistically, TM6SF2 directly bound to IKKβ and inhibited NF-κB signalling pathway to reduce interleukin (IL)-6 secretion, thereby activating cytotoxic CD8⁺ T cells. IL-6 neutralisation abolished the tumour-promoting and immunosuppressive effects of <i>Tm6sf2</i> knockout in mice. Moreover, introducing <i>Tm6sf2</i> by adenovirus improved immunotherapy response against MASLD-HCC in mice.</p><p><strong>Conclusion: </strong>Hepatic TM6SF2 protects against MASLD-HCC and activates cytotoxic CD8⁺ T cells via NF-κB-IL-6 axis. TM6SF2 is a promising strategy for sensitising MASLD-HCC to immunotherapy.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":23.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817803","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":"Antiviral therapy for chronic hepatitis delta: new insights from clinical trials and real-life studies","authors":"Pietro Lampertico, Maria Paola Anolli, Dominique Roulot, Heiner Wedemeyer","doi":"10.1136/gutjnl-2024-332597","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-332597","url":null,"abstract":"Chronic hepatitis D (CHD) is the most severe form of viral hepatitis, carrying a greater risk of developing cirrhosis and its complications. For decades, pegylated interferon alpha (PegIFN-α) has represented the only therapeutic option, with limited virological response rates and poor tolerability. In 2020, the European Medicines Agency approved bulevirtide (BLV) at 2 mg/day, an entry inhibitor of hepatitis B virus (HBV)/hepatitis delta virus (HDV), which proved to be safe and effective as a monotherapy for up to 144 weeks in clinical trials and real-life studies, including patients with cirrhosis. Long-term BLV monotherapy may reduce decompensating events in patients with cirrhosis. The combination of BLV 2 mg with PegIFN-α increased the HDV RNA undetectability rates on-therapy but not off-therapy, compared with PegIFN monotherapy. However, combination therapy, but not BLV monotherapy, may induce hepatitis B surface antigen (HBsAg) loss in some patients. The PegIFN lambda study has been discontinued due to liver toxicity issues, while lonafarnib boosted with ritonavir showed limited off-therapy efficacy in a phase 3 study. Nucleic acid polymer-based therapy is promising but large studies are still lacking. New controlled trial data come from molecules, such as monoclonal antibodies and/or small interfering RNA, that target HBsAg or HBV RNAs, which demonstrated not only profound HDV suppression, but also HBsAg decline. While waiting for new compounds to be approved as monotherapy or in combination, BLV monotherapy 2 mg/day remains the only approved therapy for CHD, at least in the European Union region.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"230 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809079","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":"Smoking-related <i>Lactobacillus</i> and immune cell infiltration in colorectal cancer: evidence from a population-based study.","authors":"Silu Chen, Junyi Xin, Dongying Gu, Huiqin Li, Rui Zheng, Shuwei Li, Zhengdong Zhang, Mulong Du, Meilin Wang","doi":"10.1136/gutjnl-2023-331865","DOIUrl":"10.1136/gutjnl-2023-331865","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"e3"},"PeriodicalIF":23.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140157965","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}