Gut最新文献

{"title":"Unravelling lipidomic disruptions across multiple tissues in <i>Chd8</i>-mutant ASD mice through integration of lipidomics and single-cell transcriptomics.","authors":"You Yu, Bing Zhang, Ning Wang, Zhenqiang Zuo, Peifeng Ji, Fangqing Zhao","doi":"10.1136/gutjnl-2024-332972","DOIUrl":"10.1136/gutjnl-2024-332972","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"684-686"},"PeriodicalIF":23.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365059","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":"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":"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":"539-546"},"PeriodicalIF":23.0,"publicationDate":"2025-03-06","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":"Exploring the role of genetics, gut microbiota and blood metabolites in IBD.","authors":"Yiwen Yuan, Xi Fu, Yiqun Deng, Yu Sun","doi":"10.1136/gutjnl-2024-333611","DOIUrl":"10.1136/gutjnl-2024-333611","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"690-691"},"PeriodicalIF":23.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375387","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":"Environmental and healthcare trade-offs between single-use and reusable gastroscopes.","authors":"Jiashu Han, Dan Shan","doi":"10.1136/gutjnl-2024-333827","DOIUrl":"10.1136/gutjnl-2024-333827","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"689-690"},"PeriodicalIF":23.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365060","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":"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":"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":"639-651"},"PeriodicalIF":23.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12014897/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vasomics of the liver","authors":"Chengyan Wang, Eric Felli, Jonathan Andrew Fallowfield, Christoph Frank Dietrich, Don Rockey, Jürgen Hennig, Gao-Jun Teng, Jordi Gracia-Sancho, Xiaolong Qi","doi":"10.1136/gutjnl-2024-334133","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334133","url":null,"abstract":"Chronic liver disease is a cluster of disorders associated with complex haemodynamic alterations, which is characterised by structural and functional disruptions of the intrahepatic and extrahepatic vasculature. ‘Vasomics’ is an emerging omics discipline that comprehensively analyses and models the vascular system by integrating pathophysiology of disease, biomechanics, medical imaging, computational science and artificial intelligence. Vasomics is further typified by its multidimensional, multiscale and high-throughput nature, which depends on the rapid and robust extraction of well-defined vascular phenotypes with clear clinical and/or biological interpretability. By leveraging multimodality medical imaging techniques, vascular functional assessments, pathological image evaluation, and related computational methods, integrated vasomics provides a deeper understanding of the associations between the vascular system and disease. This in turn reveals the crucial role of the vascular system in disease occurrence, progression and treatment responses, thereby supporting precision medicine approaches. Pathological vascular features have already demonstrated their key role in different clinical scenarios. Despite this, vasomics is yet to be widely recognised. Therefore, we furnished a comprehensive definition of vasomics providing a classification of existing hepatic vascular phenotypes into the following categories: anatomical, biomechanical, biochemical, pathophysiological and composite.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"18 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560788","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":"Margin thermal ablation eliminates size as a risk factor for recurrence after piecemeal endoscopic mucosal resection of large non-pedunculated colorectal polyps","authors":"Julia L Gauci, Francesco Vito Mandarino, Clarence Kerrison, Anthony M Whitfield, Timothy O’Sullivan, Sunil Gupta, Brian Lam, Varan Perananthan, Oliver Cronin, Eric Y Lee, Steven J Williams, Nicholas Burgess, Michael J Bourke","doi":"10.1136/gutjnl-2024-333563","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333563","url":null,"abstract":"Background Lesion size is an independent risk factor for recurrence following endoscopic mucosal resection of large (≥20 mm) non-pedunculated colorectal polyps. Post-resection margin thermal ablation (MTA) reduces the risk of recurrence. Its impact on the uncommon larger (≥40 mm) lesions is unknown. Objective We sought to analyse the impact of MTA on ≥40 mm lesions in a large, prospective cohort. Design A prospective cohort of patients with colorectal polyps ≥20 mm treated with piecemeal endoscopic mucosal resection in an expert tissue resection centre was divided into three phases: ‘pre-MTA’, July 2009–June 2012; ‘MTA-adoption’, July 2012–June 2017 and ‘standardised-MTA’, July 2017–July 2023. Recurrence was defined as adenomatous tissue endoscopically and/or histologically detected at the first surveillance colonoscopy. The primary outcome was the recurrence rate over the three time periods in three size groups: 20–39 mm, 40–59 mm and ≥60 mm. Results Over 14 years until July 2023, 1872 sporadic colorectal polyps ≥20 mm in 1872 patients underwent endoscopic mucosal resection (median lesion size 35 mm (IQR 25–45mm)). Of these, 1349 patients underwent surveillance colonoscopy at a median of 6 months (IQR 4–8 months). The overall rates of recurrence in the pre-MTA, MTA-adoption and standardised-MTA phases were 13.5% (n=42/310), 12.6% (n=72/560) and 2.1% (n=10/479), respectively, (p≤0.001). When MTA was applied in the standardised-MTA phase, the rate of recurrence was the same among 20–39 mm (1.5% (3/205)), 40–59 mm (1.6% (3/190)) and ≥60 mm polyps (1.4% (1/73)) (p=1.00). Conclusion MTA negates the effect of size on the incidence of recurrence after piecemeal endoscopic mucosal resection of colorectal polyps ≥40 mm. Trial registration number Australian Colonic Endoscopic Resection cohort ([NCT01368289][1]; [NCT02000141][2]). Data are available upon reasonable request. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01368289&atom=%2Fgutjnl%2Fearly%2F2025%2F03%2F05%2Fgutjnl-2024-333563.atom [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02000141&atom=%2Fgutjnl%2Fearly%2F2025%2F03%2F05%2Fgutjnl-2024-333563.atom","PeriodicalId":12825,"journal":{"name":"Gut","volume":"91 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560928","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 green mark really recyclable?","authors":"Shintaro Fujihara, Hideki Kobara, Atsushi Imagawa","doi":"10.1136/gutjnl-2025-335142","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-335142","url":null,"abstract":"I read the paper by López-Muñoz et al 1 on ‘Life cycle assessment of routinely used endoscopic instruments and simple intervention to reduce our environmental impact’ with great interest. The green mark setting for parts that do not come into contact with the endoscope’s operating channel is a very simple and convenient method that can be carried out on site, and it was shown that the environmental impact of the equipment could be greatly reduced by recycling. However, as we read the paper, two questions came to mind. First, there is a possibility that the risk of nosocomial contamination was underestimated. There is insufficient evidence to show that the separation of equipment using the green mark system meets infection control standards. To evaluate the safety of the method and the risk of the nosocomial contamination of the biopsy forceps that are recycled, we conducted a simple bacteriological evaluation and measurements of ATP in a limited number of cases (figure 1A). In …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"211 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539205","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":"Bioprinting functional hepatocyte organoids derived from human chemically induced pluripotent stem cells to treat liver failure","authors":"Guangya Li, Jianyu He, Jihang Shi, Xinyi Li, Lulu Liu, Xinlan Ge, Wenhan Chen, Jun Jia, Jinlin Wang, Ming Yin, Yasuyuki Sakai, Wei Sun, Hongkui Deng, Yuan Pang","doi":"10.1136/gutjnl-2024-333885","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333885","url":null,"abstract":"Background To treat liver failure, three-dimensional (3D) bioprinting is a promising technology used to construct hepatic tissue models. However, current research on bioprinting of hepatic tissue models primarily relies on conventional single-cell-based bioprinting, where individual functional hepatocytes are dispersed and isolated within hydrogels, leading to insufficient treatment outcomes due to inadequate cell functionality. Objective Here, we aim to bioprint a hepatic tissue model using functional hepatocyte organoids (HOs) and evaluate its liver-specific functions in vitro and in vivo . Design Human chemically induced pluripotent stem cells (hCiPSCs) were used as a robust and non-genome-integrative cell source to produce highly viable and functional HOs (hCiPSC-HOs). An oxygen-permeable microwell device was used to enhance oxygen supply, ensuring high cell viability and promoting hCiPSC-HOs maturation. To maintain the long-term biofunction of hCiPSC-HOs, spheroid-based bioprinting was employed to construct hepatic tissue models (3DP-HOs). 3DP-HOs were intraperitoneally implanted in mice with liver failure. Results 3DP-HOs demonstrated enhanced cell viability when compared with a model fabricated using single-cell-based bioprinting and exhibited gene profiles closely resembling hCiPSC-HOs while maintaining liver-specific functionality. Moreover, 3DP-HOs implantation significantly improved survival in mice with CCl4-induced acute-on-chronic liver failure and also Fah−/− mice with liver failure. 3DP-HOs significantly reduced liver injury, inflammation and fibrosis indices while promoting liver regeneration and biofunction expression. Conclusion Our bioprinted hepatic tissue model exhibits remarkable therapeutic efficacy for liver failure and holds great potential for clinical research in the field of liver regenerative medicine. All data relevant to the study are included in the article or uploaded as supplementary information.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"28 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538437","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":"Gut microbiota-related neuroinflammation at the crossroad of food reward alterations: implications for eating disorders.","authors":"Sabrina J P Huwart, Nuria Morales-Puerto, Amandine Everard","doi":"10.1136/gutjnl-2024-333397","DOIUrl":"10.1136/gutjnl-2024-333397","url":null,"abstract":"<p><p>The link between gut microbiome and eating behaviours, especially palatable food intake, is a growing focus of scientific investigation. The complex ecosystem of microorganisms in the gut influences host metabolism, immune function and neurobehavioural signalling. This review explores the role of neuroinflammation in dysregulations of food-induced reward signalling and the potential causal role of the gut microbiota on these proinflammatory processes. Particular attention is given to eating disorders (ED, specifically anorexia nervosa, binge eating disorder and bulimia nervosa) and potential links with the gut microbiota, food reward alterations and neuroinflammation. Finally, we propose gut microbiota modulation as a promising therapeutic strategy in food reward alterations and ED.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":23.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440650","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}