Gut最新文献

{"title":"AI-empowered human microbiome research","authors":"Tian Zhou, Fangqing Zhao","doi":"10.1136/gutjnl-2025-335946","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-335946","url":null,"abstract":"Recent advances in high-throughput microbiome profiling have generated expansive data sets that offer unprecedented opportunities to investigate the role of microbes in human health. However, the complexity and high dimensionality of these data present significant analytical challenges that often exceed the capabilities of traditional computational methods. Artificial intelligence (AI), encompassing both classical machine learning and modern deep learning approaches, has emerged as a powerful solution to these challenges. In this review, we systematically explore AI-driven methodologies in microbiome research, including clustering algorithms, dimensionality reduction techniques, convolutional and recurrent neural networks, and emerging large language models. We assess how these approaches enable the extraction of meaningful biological patterns from complex microbial data from a multiscale perspective, facilitating insights into community dynamics, host–microbe interactions and functional genomics. Additionally, we explore the transformative impact of AI on translational applications across both academic research and real-world clinical settings, including disease diagnostics, therapeutic development and precision microbiome engineering. By critically evaluating the current capabilities and limitations of AI in this context, this review aims to chart a path forward for the integration of AI into microbiome research, ultimately accelerating innovations in personalised medicine and deepening our understanding of host–microbiome relationships.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"9 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145116156","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":"Gastrin-dependent expansion of Cck2r+ corpus progenitors accelerates ulcer healing and inhibits gastric dysplasia","authors":"Biyun Zheng, Hiroki Kobayashi, Ruhong Tu, Kexuan Huang, Xiaofei Zhi, Guodong Lian, Feijing Wu, Jin Qian, Yosuke Ochiai, Quin T Waterbury, Ermanno Malagola, Jiaoqian Lu, Masahiro Hata, Yi Zeng, Hualong Zheng, Puran Zhang, Shuang Li, Leah Zamechek, Xiaozhong Wang, Fenglin Chen, Timothy C Wang","doi":"10.1136/gutjnl-2025-335103","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-335103","url":null,"abstract":"Background The cholecystokinin-2/gastrin receptor (Cck2r) is expressed in corpus isthmus progenitor, enterochromaffin-like and parietal cells, regulating acid secretion and cell turnover. However, the role of gastrin on Cck2r progenitors during mucosal regeneration remains unexplored. Objective To study the role of gastrin-Cck2r axis and corpus progenitors during gastric injury and regeneration. Design We generated Cck2r-CreERT2; Gastrin-DTR-p2A-TdTomato; Rosa26-ZsGreen mice to trace corpus Cck2r+ progenitors during homeostasis and injury, under conditions of hypogastrinaemia and hypergastrinaemia. Injury models included acute ulceration, chronic H. pylori gastritis and N-Nitroso-N-Methylurea (MNU) exposure. Results Hypergastrinaemia significantly expanded Cck2r+ isthmus progenitors, whereas hypogastrinaemia reduced them. Gastric ulceration induced a twofold elevation in plasma gastrin by day 14, antral G-cell expansion and complete ulcer healing by day 28. Gastrin infusion or proton pump inhibitor (PPI) treatment further elevated gastrin and promoted complete ulcer healing by day 14, whereas G-cell ablation minimised gastrin, impaired healing and abrogated the benefits of PPI (p < 0.05). The vagus nerve, through the muscarinic receptor 3, mediated both gastrin elevations and Cck2r+ progenitor expansion during ulcer healing. G-cell ablation in H. pylori -infected mice increased colonisation and exacerbated inflammation, atrophy, metaplasia and dysplasia (p < 0.05), while hypergastrinaemia was protective. Similarly, in the MNU model, G-cell ablation worsened gastric pathology while hypergastrinaemia mitigated it. Conclusions We report a novel role for G-cell-derived gastrin in ulcer healing. Hypogastrinaemia is a risk factor for poor ulcer healing, corpus atrophy and potentially cancer, while physiological gastrin responses are protective. PPI-induced hypergastrinaemia plays a key role in ulcer healing, and gastrin signalling may prevent gastric preneoplasia. All data relevant to the study are included in the article or uploaded as supplementary information.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"39 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145116155","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":"Alleviated T cell exhaustion and SLC1A3-mediated stroma-remodelling dictate chemoimmunotherapy efficacy in oesophageal squamous cell carcinoma","authors":"Shujing Xiang, Yanxing Chen, Chaoye Wang, Min Wang, Ye He, Zhichao Liu, Jin-Ling Zhang, Lu-Ping Yang, Yun-Fu Wei, Qi-Nian Wu, Zi-Xian Wang, Shao-Yan Xi, Zhigang Li, Qi Zhao, Rui-Hua Xu, Feng Wang","doi":"10.1136/gutjnl-2025-335642","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-335642","url":null,"abstract":"Background Combining chemotherapy with anti-programmed cell death protein-1 (PD-1) improves clinical outcomes in oesophageal squamous cell carcinoma (ESCC), yet the underlying synergistic mechanism remains obscured. Moreover, 30–50% of patients still derive no therapeutic benefit from the combination strategy, highlighting the need to decipher and overcome resistance. Objective We sought to investigate the mechanisms by which chemotherapy augments the responses to immune checkpoint blockade and elucidate the factors contributing to persistent resistance in non-responding patients. Design We designed a systematic investigation involving longitudinal sampling of ESCC tissues both from patients treated with chemotherapy plus anti-PD-1 and anti-PD-1 monotherapy. The tumour microenvironment (TME) was then comprehensively characterised using single-cell transcriptomics, T cell receptor repertoire analysis, multiplex immunohistochemistry and murine models. Results We demonstrated that combination therapy exerted superior antitumour efficacy by mitigating immune checkpoint engagements (TIGIT-NECTIN2 and NECTIN1-CD96) between epithelial-stress tumour cells and CD8+ T cells, thereby preventing T cells from exhaustion and boosting vitality. In non-responders, we identified a subset of tumour cells with high SLC1A3 expression, which localised at the tumour boundary and interacted with COL1A1+ myofibroblastic cancer-associated fibroblasts, inducing an extracellular matrix-enriched TME that hindered the infiltration of CD8+ T cells. Inhibiting SLC1A3 significantly enhanced the efficacy of chemotherapy plus anti-PD-1, underscoring its potential as a therapeutic target. Conclusion This study elucidates the synergistic mechanisms and identifies key resistance pathways underlying chemo-immunotherapy combinations in patients with ESCC, providing a scientific basis for refining future combination therapeutic regimens. Data are available in a public, open access repository. Data are available upon reasonable request. The curated high-quality scRNA-seq data, scTCR-seq of ESCC patient samples and mouse scRNA-seq data were deposited at in the Genome Sequence Archive at the National Genomics Data Center with accession numbers: PRJCA037418. The raw sequencing data of validated ESCC scRNA-seq cohort and bulk RNA-seq of Li et al 2023 ESCC cohort could be obtained in the Genome Sequence Archive at the National Genomics Data Center with accession numbers: PRJCA012636[20][1]. Any additional information required to reanalyse the data reported in this paper is available from the lead contact upon reasonable request. [1]: #ref-20","PeriodicalId":12825,"journal":{"name":"Gut","volume":"90 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145116190","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":"Differentiating gastroparesis from functional dyspepsia is no longer sufficient","authors":"Gregory O’Grady, Chris Varghese, Christopher N Andrews, Armen A Gharibans","doi":"10.1136/gutjnl-2025-336908","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-336908","url":null,"abstract":"We read with interest the commentary by Camilleri and Talley on whether gastroparesis and functional dyspepsia (FD) are ‘really ‘interchangeable’ diseases’.1 Their significant efforts to improve the reliability of gastric emptying testing will strengthen both care and trials. However, we submit that their careful analysis also serves as a starting point for deeper inquiry, because differentiation by emptying testing alone is no longer sufficient. It is now widely accepted that both FD and gastroparesis labels reflect umbrella syndromes grouping diverse underlying pathophysiologies. These underlying mechanisms are shared by both syndromes, but vary between individual patients. Some are motor, some are sensory, some overlap. They include interstitial cell of Cajal (ICC) deficits, impaired accommodation, autonomic and pyloric dysfunction, antral hypomotility, immune activation, hypersensitivity and gut-brain axis dysregulation.2 Several such factors may delay gastric emptying, but delayed emptying is specific to none of them. Emptying is thus best appreciated as an integrative measure of gastric function, and while clinically important, only captures one disease axis among many. Confronting these overlapping and heterogeneous mechanisms is essential, because it helps explain decades of …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"39 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089669","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":"Biliary sludge and microlithiasis: are we covering the full spectrum of lithogenic biliary disorders?","authors":"Igor Mendonça Proença, Marcos E Lera dos Santos, Fauze Maluf-filho","doi":"10.1136/gutjnl-2025-336609","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-336609","url":null,"abstract":"We read with great interest the recent consensus by Żorniak et al ,1 which provides a long-awaited standardised definition of biliary sludge and microlithiasis. 30 internationally recognised experts participated in a structured survey and voting process, leading to proposed definitions: microlithiasis as ‘hyperechoic calculi≤5 mm with acoustic shadowing’, biliary sludge as ‘hyperechoic material without acoustic shadowing, sedimenting in the dependent part of the gallbladder’ and biliary stones as ‘calculi>5 mm with acoustic shadowing’. This represents an important step towards harmonising terminology and enabling future clinical studies. In routine endoscopic ultrasound (EUS) practice, …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"4 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089620","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":"Dissecting the immune pathogenesis of HBV-ACLF through single-cell multimodal analysis.","authors":"Frank Tacke,Jonel Trebicka","doi":"10.1136/gutjnl-2025-336545","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-336545","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":"56 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083532","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":"Lumen-apposing metal stents for pancreatic fluid collections: has advancing technology encouraged over-reach?","authors":"Besim Fazıl Ağargün,Bilger Cavus,Asli Cifcibasi Ormeci,Kadir Demir","doi":"10.1136/gutjnl-2025-336668","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-336668","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":"312 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083534","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":"Glycaemic control is a modifiable risk factor for pancreatic cancer development in patients with diabetes: a population-based cohort study.","authors":"Jing Tong Tan,Xianhua Mao,David Tak-Wai Lui,Chang Li,Ho-Ming Cheng,Wai-K Leung,Wai-Kay Seto,Ka-Shing Cheung","doi":"10.1136/gutjnl-2025-335837","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-335837","url":null,"abstract":"BACKGROUNDEffect of glycaemic control on pancreatic cancer (PC) development in patients with long-standing type 2 diabetes (T2D) remains unclear.OBJECTIVETo investigate effects of glycaemic control on PC development in patients with T2D.DESIGNRetrospective cohort study.METHODSAdults from a territory-wide healthcare registry were followed from T2D diagnosis until PC, death, pancreatectomy or end of study (December 2020). Exclusions were PC within 3 years after T2D diagnosis (addressing reverse causality), prior PC, immunoglobulin G4 disease and pancreatectomy. The primary outcome was PC and secondary outcomes included PC-related and all-cause mortality. Optimal glycaemic control throughout follow-up was defined as time-weighted mean haemoglobin A1c (A1c)<7%; with time-weighted mean fasting glucose (FG)≤7 mmol/L as secondary analysis. Adjusted HR (aHR) was estimated using Cox models with propensity score adjustment for covariates including demographics, diabetes complications, comorbidities and medications.RESULTSAmong 458 331 patients (median age: 59.8 (P25-P75: 51.8-68.5) years; 51.2% male), there were 1382 (0.3%; 2.8 per 10 000 person-years) PC, 922 (0.2%; 1.9 per 10 000 person-years) PC-related deaths, and 70 936 (15.5%; 142.9 per 10 000 person-years) deaths over a median follow-up of 9.9 (P25-P75: 7.4-14.1) years. Optimal glycaemic control was associated with lower PC risk-A1c<7%(aHR: 0.43; 95% CI: 0.37 to 0.48) and FG≤7 mmol/L (aHR: 0.71; 95% CI: 0.63 to 0.80). Optimal control of both A1c and FG conferred lowest PC risk (aHR: 0.39; 95% CI: 0.33 to 0.46). PC risk increased stepwise with A1c (Ptrend<0.001), with aHRs from 1.85 (A1c 7.0-7.5%) to 4.61 (A1c≥9.0%). Every 1% rise in A1c and 1 mmol/L rise in FG increased PC risk by 46% and 14%, respectively. Optimal control is also associated with lower PC-related mortality (aHR: 0.35; 95% CI: 0.30 to 0.41) and all-cause mortality (aHR: 0.83; 95% CI: 0.82 to 0.85).CONCLUSIONOptimal glycaemic control was associated with lower PC risk in T2D. Further multicentre cohort studies are warranted to confirm its oncopreventive strategy.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"37 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083533","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":"Setting a vision for British Society of Gastroenterology guidelines: embracing innovation while preserving methodological excellence and clinical utility.","authors":"Matthew Kurien,Elizabeth Bird-Lieberman,Shahida Din,Harriet Gordon,Christopher Andrew Lamb,Colin J Rees","doi":"10.1136/gutjnl-2025-336942","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-336942","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":"16 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083531","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 microbiome comparability between DNA extraction kits.","authors":"Gregory R Young,Nurulamin Noor,Aryan Khirwadkar,Lauren C Beck,Mohmmed Tauseef Sharip,Kevin Whelan,Nicholas A Kennedy,Jack Satsangi,Julian Marchesi,Luke Jostins-Dean,Christopher Stewart,Paul A Lyons,Miles Parkes,Christopher Andrew Lamb, ","doi":"10.1136/gutjnl-2025-336648","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-336648","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":"37 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145071855","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}