Gut最新文献

{"title":"Response to Abdulrahman Qatomah et al and Suchanart Jitrukthai et al","authors":"Akihiro Miyakawa, Yuzuru Tamaru, Takeshi Mizumoto, Noriyoshi Kanazawa, Shiori Uchiyama, Kosuke Maehara, Yorinobu Sumida, Akira Nakamura, Ei Itobayashi, Haruhisa Shimura, Yoshio Suzuki, Tomoyuki Akita, Kenji Shimura, Toshio Kuwai","doi":"10.1136/gutjnl-2025-336740","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-336740","url":null,"abstract":"We sincerely thank Abdulrahman Qatomah et al and Suchanart Jitrukthai and Kaosombatwattana for their interest in our study and for their insightful comments.1–3 The overall and severe delayed bleeding rates may appear slightly elevated from a real-world clinical standpoint. However, in this study, patients with overall delayed bleeding were classified into two groups: severe and mild delayed bleeding groups. Severe delayed bleeding was defined as haematochezia that required endoscopic haemostasis or blood transfusion, whereas mild delayed bleeding was defined as haematochezia that required no haemostasis or transfusion. Thus, the definition of severe delayed bleeding in this study is similar to the criteria used in the previous reports. The mild delayed bleeding group included cases of haematochezia resulting from residual blood or slight bleeding. Although not life-threatening, we believe that reducing the …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"29 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228761","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’ response","authors":"Aniruddha Pratap Singh, Duvvur Nageshwar Reddy, Sundeep Lakhtakia","doi":"10.1136/gutjnl-2025-337052","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-337052","url":null,"abstract":"We thank Zhang et al for their interest in our study and for their thoughtful comments on the accuracy of endoscopic ultrasound-guided portal vein pressure (EUS-PVP) measurements.1 The letter raises several important methodological considerations that merit clarification. First, regarding the observed moderate correlation (Pearson coefficient 0.72) between the compact manometer (CM) and the conventional ECG monitor with central venous pressure (CVP) module connected via a pressure transducer (CPT) for preoperative EUS-PVP measurements, we agree that this is not as strong as the excellent intraoperative correlation (0.96). However, this discrepancy may have arisen from procedural variations rather than inherent inaccuracies in the technique. All EUS-PVP measurements were performed in the left lateral position under monitored anaesthesia care with propofol, using the long position of the EUS scope, which may increase resistance. In our study, zeroing was performed at the phlebostatic …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"77 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228764","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":"Response to ‘Biliary sludge and microlithiasis: are we covering the full spectrum of lithogenic biliary disorders?’","authors":"Simon Sirtl, Michal Zorniak, Julia Mayerle","doi":"10.1136/gutjnl-2025-337089","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-337089","url":null,"abstract":"We thank Mendonça Proença et al 1 for their thoughtful and constructive comments on our recently proposed consensus definition of biliary sludge and microlithiasis.2 We fully agree that only a globally standardised definition of sludge and microlithiasis will allow for high-quality prospective studies, thereby clarifying their pathophysiological relevance for both the development and recurrence of acute pancreatitis. The fourth category of biliary dust proposed by the authors, in addition to sludge, microlithiasis and gallstones, is intriguing but, in our view, not meaningful for several reasons. Not least, the PICUS-1 study demonstrated that diagnostic endoscopic ultrasound (EUS) is the first-line …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"158 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228762","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":"Current and emerging concepts for systemic treatment of metastatic colorectal cancer","authors":"Christoph Steup, Kilian Kennel, Markus F Neurath, Stefan Fichtner-Feigl, Florian Greten","doi":"10.1136/gutjnl-2025-335412","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-335412","url":null,"abstract":"Colorectal cancer (CRC) is one of the most common malignant cancers and its incidence is steadily rising particularly in young patients. While screening measures and the widespread availability of surgical treatment have led to an impressive improvement of prognosis within the overall CRC population, patients with metastatic CRC still face 5-year survival rates of around 10–25%. Despite continuous development of new systemic treatment strategies that include cytotoxic chemotherapy and targeted therapy, most patients with metastatic CRC eventually progress. However, a small proportion of patients with mismatch repair-deficient or microsatellite unstable CRC responds exceptionally well to treatment with immune checkpoint inhibitors, thereby proving that CRC is in principle amenable to immunotherapy and showing that long-term disease stabilisation can be achieved even in metastasised stages. However, the reasons for the lack of response to immunotherapy in the vast majority of CRC cases remain to be elucidated. Yet, recent evidence suggests that the tumour stroma, which includes non-immune cells in the colorectal tumour microenvironment, mediates immunosuppressive mechanisms that prevent effective immunotherapy. These findings open new avenues for the development of advanced immunotherapies for CRC. In this review, we summarise major developments in the systemic therapy of CRC within the last couple of decades, provide an overview of emerging and soon-to-be implemented therapeutic strategies and present concepts from clinical and preclinical research to manipulate tumour cells and the tumour stroma to sensitise microsatellite stable colorectal tumours to immunotherapy.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"15 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228765","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":"Improving evidence, but at what ethical price?","authors":"Daisuke Murakami, Masayuki Yamato, Makoto Arai","doi":"10.1136/gutjnl-2025-336625","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-336625","url":null,"abstract":"We read with interest the article by Miyakawa et al reporting that prophylactic clip closure after colorectal endoscopic submucosal dissection (ESD) reduces severe delayed bleeding.1 While recent correspondence highlights methodological concerns regarding the unusually high bleeding rate in the non-closure group,2 3 we would like to further raise concerns about the ethical aspects of the study design. Prior randomised controlled trials (RCTs), meta-analyses and US guidelines already support prophylactic closure after endoscopic mucosal resection (EMR) for proximal colon lesions≥20 mm.4–6 Despite this evidence, the present study randomised patients undergoing colorectal ESD—including those with 20–50 mm lesions in the right colon—into closure and …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"103 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228763","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":"Impaired glucose metabolism in irritable bowel syndrome: personalised low-glycaemic diet as potential therapeutic target","authors":"Franziska Schmelter, Torsten Schröder, Yves Laumonnier, OUTLIVE-CRC consortium, Stephan C Bischoff, Stefanie Derer, Benjamin Anderschou Holbech Jensen, Christian Sina","doi":"10.1136/gutjnl-2025-336797","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-336797","url":null,"abstract":"We read with great interest the recent study by Gilliam-Vigh et al demonstrating significant transcriptomic alterations in the intestinal mucosa of individuals with type 2 diabetes (T2D), particularly increased immune activation, altered barrier function in the large intestine and metabolic dysfunction.1 These findings provide crucial mechanistic insights that complement observations on metabolic disturbances in patients with irritable bowel syndrome (IBS), supporting the rationale for glucose-targeted interventions. Given the substantial interindividual variability in glycaemic responses,2 we investigated the therapeutic potential of a personalised low-glycaemic diet (PLGD) in IBS management. In our nutritional observation study of 20 age and gender-matched patients with IBS, we compared clinical outcomes between those receiving either a PLGD or the established low-FODMAP diet (LFD) over a minimum 3-month period (figure 1). Figure 1 Precomparison and postcomparison in IBS Severity Scoring System (IBS-SSS) between age- and gender-matched patients with IBS receiving either a personalised low-glycaemic diet (PLGD, n=10) or a standard therapy low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet (LFD, n=10) using paired Wilcoxon test. The group means are represented by a dashed line, and an arrow represents the reduction in IBS-SSS, with a reduction between 50 and 230 points in PLGD and between 30 and 290 points in LFD. *P<0.05. Remarkably, our personalised nutrition (PN) approach achieved symptom improvement comparable to standard LFD, assessed …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"49 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228766","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":"DPP-4 inhibitor alleviates gut-brain axis pathology in Parkinson’s disease","authors":"Seong Ho Jeong, Yeon Ju Kim, Jin Young Shin, Kyu Won Oh, Jung Wook Lee, Phil Hyu Lee","doi":"10.1136/gutjnl-2025-334988","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-334988","url":null,"abstract":"Background Dipeptidyl peptidase-4 inhibitors (DPP-4is) have been reported to exhibit therapeutic effects in Parkinson’s disease (PD), increasing their potential for drug repurposing. One aspect of PD pathogenesis is thought to be associated with the gut-brain axis, where α-synuclein from the gut is transmitted to the brain via the vagus nerve (VN). Objective We explored whether sitagliptin, a DPP-4i, exhibits a protective effect in a low-dose rotenone-treated gut-brain axis-associated PD model. Design To explore the effect of sitagliptin, we used the oral rotenone-treated mouse model, which showed spreading of pathological α-synuclein from the intestine in a stereotypic manner via the VN into the midbrain with motor deficits. Results Sitagliptin mitigated rotenone-induced gut inflammation and toll-like receptor 2 (TLR2) expression, reduced α-synuclein accumulation in the gut, VN and brain and lessened neuronal loss in the medulla and midbrain with recovery of motor performance. In addition, sitagliptin suppressed inflammation in response to a TLR2 agonist and rotenone in macrophages, enteric glial cells and enteroendocrine cell lines in vitro. In secretin tumour cell 1, an enteroendocrine cell line, sitagliptin also decreased rotenone-induced endogenous α-synuclein levels. The beneficial effects of sitagliptin were maintained even under glucagon-like peptide-1 receptor blockade. Notably, sitagliptin significantly altered the gut microbiome, shifting towards a profile that may counteract PD pathology. Conclusion These findings demonstrated that sitagliptin alleviated α-synuclein deposition in the gut and brain through modulation of TLR2-mediated inflammation and altered the gut microbiome composition towards a more favourable profile, which indicates that DPP-4is can offer a novel therapeutic avenue for managing PD. Data are available on reasonable request.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"110 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209959","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":"Biology of regional gut-mucosal-transcriptomes in healthy individuals and individuals with diabetic: incorporating cellular composition and embracing variation","authors":"Michiel Kleerebezem","doi":"10.1136/gutjnl-2025-336401","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-336401","url":null,"abstract":"Hannah Gilliam-Vigh and coworkers1 highlight that regional transcriptome differences are much larger than the difference between healthy and diseased individuals. Moreover, a substantially larger degree of regional difference was observed in the small intestine compared to the large intestine, inspiring separate intraregional transcriptome analyses for the small and large intestinal samples to enhance the resolution of detection of differentially expressed genes (DEG) in the large intestine. Clustering of regional transcription landscapes in the small intestine identified six distinct region-expression profiles that confirm expected regional distinctions of gut-metabolic and immune system-related functions. A striking example is the clear coincidence between the elevated expression of lipid catabolism processes in the small intestinal regions predominantly responsible for fat absorption (jejunum and early ileum). Likewise, expression of immune system associated pathways clearly peaked in the distal regions of the small intestine, colocalising with the known enrichment of Peyer’s patches and emphasising the predominant role of this part of the intestine in immune surveillance. Likewise, one of the four regional transcription clusters detected in the colon indicates a gradual increase in glycoprotein metabolism expression when progressing from caecum to rectum, …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"95 1 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209965","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":"FODMAPs and functional dyspepsia: emerging evidence but unanswered questions","authors":"Christopher Black, Heidi Staudacher","doi":"10.1136/gutjnl-2025-336428","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-336428","url":null,"abstract":"Functional dyspepsia (FD) is a common disorder of gut-brain interaction (DGBI) characterised by symptoms of epigastric pain or burning, referred to as epigastric pain syndrome, and bothersome postprandial fullness or early satiation, referred to as postprandial distress syndrome (PDS).1 Colloquially, of course, such symptoms are described by patients as ‘indigestion’ and, given their meal-related nature, it is perhaps unsurprising that symptoms are often attributed to food. Indeed, patients with dyspepsia often prioritise identifying dietary triggers for their symptoms. Advice to avoid alcohol, as well as spicy or fatty foods, for example, is common. However, this is based on little evidence, and there are few studies of exclusion diets in FD. Conversely, in irritable bowel syndrome (IBS), another DGBI that frequently overlaps with FD, a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) is widely used.2 FODMAPs are short-chain carbohydrates that are poorly digested or absorbed in the small intestine, leading to osmotic effects. FODMAPs also undergo fermentation by colonic bacteria. Hence, restricting FODMAP intake can improve abdominal pain, diarrhoea and bloating in IBS. In Gut , Van den Houte et al have evaluated a low FODMAP diet (LFD) for treating patients with FD, including assessing symptom recurrence using blinded reintroduction of FODMAPs administered as powders.3 Given the mechanisms of action described above for IBS related to the small intestine and colon, an LFD might not be an obvious choice for …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"24 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145195379","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":"Hypothesis-generating evaluation of multi-armoured oncolytic HSV-1 (VG161) in intrahepatic cholangiocarcinoma: pooled insights from multicentre studies","authors":"Yinan Shen, Xinyan Jin, Wei Song, Tian Fang, Yuwei Li, Zeda Zhao, Xingmei Liang, Qian Tan, Ronghua Zhao, Yuntao Zhang, William Jia, Hongwei Huang, Tengjie Wu, Guoming Shi, Zhewei Zhang, Enliang Li, Guyue Wei, Tao Jiang, Zijun Wang, Zifan Yang, Danni Lin, Linghao Xia, Sida Guo, Jiaxin Li, Fang Wei, Xueyan Shi, Siyuan Chen, Chuntian Tu, Zhanyi Shou, Longshen Xie, Hongchao Zhang, Hangyu Zhou, Peilin Lan, Jun Ding, Wei Chen, Yufu Ye, Xiaozhen Zhang, Yiwen Chen, Xiang Li, Zhenglong Zhai, Wendi Hu, Xiaoyu Zhang, Lei Wang, Xiaoli Sun, Qingwei Zhao, Xingjiang Hu, Youlei Wang, Zhuojun Zhou, Jiejing Kai, Jichen Li, Wei Zhang, Xueli Bai, Tingbo Liang","doi":"10.1136/gutjnl-2025-335904","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-335904","url":null,"abstract":"Background Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy with limited treatment options and poor prognosis, especially for patients who failed standard therapies. Objective To explore the safety, efficacy and immunological mechanisms of the novel edition of oncolytic virus vaccination, VG161, a multiarmed oncolytic herpes simplex virus-1 expressing interleukin (IL)-12, IL-15 and a programmed death-ligand 1 antagonist, in patients with advanced ICC. Design This pooled analysis integrates data from two multicentre clinical studies: a Phase I dose-escalation study and a Phase IIa exploratory study. 24 patients with advanced ICC received ultrasound-guided intratumoral injections of VG161. Multiomics analyses were performed on longitudinal tumour biopsies to evaluate immune modulation. Results The oncolytic virus therapy VG161 was well tolerated and showed encouraging antitumour activity, including improved overall survival versus second-line FOLFOX chemotherapy, even though most patients received VG161 as third-line or later therapy. Notably, patients previously treated with immune checkpoint inhibitors (CPIs) experienced enhanced benefit. Multiomics profiling of longitudinal biopsies revealed significant remodelling of the immunosuppressive tumour microenvironment, with proliferated infiltration of antigen-presenting cells, CD8+ T cell activation and M2-like macrophage depletion. Single-cell and spatial transcriptomics identified epithelial and macrophage subpopulations (Epi-C2 and Macro-C1QC) as potential biomarkers of response and resistance. Conclusion These early-phase findings suggest that VG161 elicits meaningful immune activation in ICC and supports further investigation. By inducing both direct oncolysis and multilayered immune activation, VG161 shows clinical benefit in a heavily pretreated population and holds promise for integration with CPI-based regimens. Validation in larger trials is warranted. Data are available in a public, open access repository. Data are available from the corresponding author upon reasonable request.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"26 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145188437","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}