Gut最新文献

{"title":"Outcome of a FODMAP restriction diet with subsequent blinded reintroduction in functional dyspepsia/postprandial distress syndrome","authors":"Karen Van den Houte, Bert Broeders, Joran Tóth, Karen Routhiaux, Zoë Mariën, Jasmien Van den Bergh, Julie Vanderstappen, Nelle Pauwels, Ann Meulemans, Christophe Matthys, Tim Vanuytsel, Florencia Carbone, Jan Tack","doi":"10.1136/gutjnl-2024-334156","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334156","url":null,"abstract":"Background Recent studies have shown increased duodenal mucosal permeability as a possible key player in the pathophysiology of functional dyspepsia (FD). Adverse reaction to nutrients is an important candidate underlying mechanism. Intragastric infusion of fermentable oligo-, di-, monosaccharides and polyols (FODMAPs) induced symptoms reminiscent of FD with a rapid onset. Objective We evaluated the effect of a low FODMAP diet (LFD) and individual FODMAP-triggers on symptom severity and duodenal mucosal permeability in FD. Design Patients with FD followed a 6-week LFD and filled out the validated Leuven Postprandial Distress Syndrome (LPDS) daily diary, Short Form-Nepean Dyspepsia Index (SF-NDI) Questionnaire, patient assessment of upper gastrointestinal symptoms (PAGI-SYM) and Patient Health Questionnaire (PHQ). Patients underwent an endoscopy with duodenal biopsies to define mucosal integrity by quantifying transepithelial electrical resistance (TEER) and dextran flux. LFD was followed by a blinded reintroduction during which patients were challenged by 7 powders (fructans, fructose, galacto-oligosaccharides (GOS), lactose, mannitol, sorbitol, glucose). Results 36 FD patients entered the study. LPDS improved significantly at the end of the LFD in 73%. In addition, SF-NDI, PAGI-SYM and PHQ improved significantly. Dextran flux and TEER were not significantly different, but delta TEER correlated positively with delta LPDS. A large variety of FODMAP powders was able to induce recurrence with mannitol as the most prevalent triggering FODMAP (23%). Surprisingly, 27% showed higher LPDS scores during intake of glucose. Conclusions A LFD significantly improved PDS symptoms, but this was not associated with altered mucosal integrity. Powder reintroduction identified a large variety in individual FODMAPs and glucose as triggers. Data are available on reasonable request. On request, all datasets can be provided.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"10 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915747","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":"Global consensus statement on the management of pregnancy in inflammatory bowel disease","authors":"Uma Mahadevan, Cynthia H Seow, Edward L Barnes, María Chaparro, Emma Flanagan, Sonia Friedman, Mette Julsgaard, Sunanda Kane, Siew Ng, Joana Torres, Gillian Watermeyer, Jesus Yamamoto-Furusho, Christopher Robinson, Susan Fisher, Phil Anderson, Richard Gearry, Dana Duricova, Marla Dubinsky, Millie Long","doi":"10.1136/gutjnl-2025-336402","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-336402","url":null,"abstract":"Background & aims Pregnancy can be a complex and risk filled event for women with inflammatory bowel disease (IBD). High-quality studies in this population are lacking, with limited data on medications approved to treat IBD during pregnancy. For patients, limited knowledge surrounding pregnancy impacts pregnancy rates, medication adherence, and outcomes. Limited provider knowledge leads to highly varied practices in care affected by local dogma, available resources, individual interpretation of the literature, and fear of harming the fetus. The variations in guidelines by different societies and countries reflect this and lead to confusion for physicians and patients alike. The Global Consensus Consortium is a group of 39 IBD and content experts and 7 patient advocates from 6 continents who convened to review and assess current data and come to an agreement on best practices based on these data. Methods The GRADE process was used when sufficient published data were available and the RAND process in those instances where expert opinion was needed to guide consistent practice. Recommendations were informed by the guiding principle that maternal health best supports infant health. Results The topics were divided into ten categories with 34 GRADE recommendations and 35 Consensus statements. Conclusions Overall, the goal of the group was to provide data-driven and practical guidance to improve the care of women with IBD around the globe based on the best available research.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"27 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144911190","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":"INSL5 as a newly recognised potential contributor to diarrhoea pathogenesis: more questions than answers","authors":"Mark Donowitz, Varsha Singh","doi":"10.1136/gutjnl-2025-336674","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-336674","url":null,"abstract":"The pathogenesis of chronic diarrhoeal diseases remains incompletely understood, so it is exciting when novel mechanistic insights emerge. In their recent Gut publication, Bannon et al 1 report a large elevation of the promotility enteroendocrine hormone insulin-like peptide 5 (INSL5) in the serum of patients with bile salt diarrhoea (BSD) and in a subset of patients with Irritable bowel syndrome with diarrhoea (IBS-D) without overt bile salt malabsorption, using a modified liquid chromatography-tandem mass spectrometry assay with increased sensitivity that they developed. This finding opens a new direction into …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"20 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915748","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":"Are functional dyspepsia and gastroparesis really ‘interchangeable’ diseases?","authors":"Michael Camilleri, Nicholas J Talley","doi":"10.1136/gutjnl-2025-336192","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-336192","url":null,"abstract":"Functional dyspepsia and gastroparesis are characterised by similar primary symptoms: nausea, vomiting, postprandial fullness, early satiety and upper abdominal discomfort. However, the population prevalence of the two conditions is very different. The global prevalence of functional dyspepsia (54 127 respondents from 26 countries) was 7.2% (range 2.2–12.3%).1 On the other hand, the standardised prevalence of gastroparesis in the UK (Clinical Practice Research Datalink database2) and in the USA (US national administrative health insurance claims database3) were, respectively, 13.8 (95% CI 12.6 to 15.1) and 267.7 (95% CI 264.8 to 270.7) cases per 100 000 persons, that is, 0.014–0.267%. This wide prevalence range may reflect different criteria for ‘gastroparesis’ in nationwide databases. Based on the Rochester Epidemiology Project (Olmsted County, Minnesota, USA), the age-adjusted prevalence of definite gastroparesis (delayed gastric emptying by standard scintigraphy and typical symptoms for>3 months) was 24.2 (95% CI 15.7 to 32.6) per 100 000.4 When including probable (typical symptoms and food retention on endoscopy or upper gastrointestinal study) and possible (typical symptoms alone or delayed gastric emptying by scintigraphy without gastrointestinal symptoms) gastroparesis, the overall prevalence was 50.5 (95% CI 38.1 to 62.8) per 100 000, or approximately 0.5%. Thus, the estimated population prevalence of functional dyspepsia is at least 15-fold higher than that of gastroparesis. Given the marked differences in management for the two conditions, it is essential to make an accurate diagnosis of gastroparesis when patients present with upper gastrointestinal symptoms. For example, gastric per-oral endoscopic myotomy (G-POEM) is an efficacious treatment for gastroparesis based on the only sham-control trial available5 with supportive evidence from meta-analyses of open-label studies, such as the weighted mean difference in total Gastroparesis Cardinal Symptom Index (GCSI) score of −1.56 (95% CI −1.89 to −1.24, p<0.001) in 20 studies involving 797 patients followed for 8.39±4.18 months. …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"18 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144911200","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 feeling: extracellular vesicles dictate liver’s susceptibility to colorectal cancer metastasis","authors":"Micol Eleonora Fiori","doi":"10.1136/gutjnl-2025-336108","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-336108","url":null,"abstract":"Colorectal cancer (CRC) represents a major global health issue, ranking as the third most common tumour and the second leading cause of cancer-related mortality worldwide.1 Distant metastasis is the primary cause of fatality for patients with cancer. CRC often presents as metastatic disease at diagnosis, and up to 70% of patients who undergo curative surgery of the primary tumour will eventually develop metastases. The liver is the most common site for CRC metastatic spread. Despite significant progress in surgical interventions and treatments, a large number of patients with CRC have inoperable liver metastases or experience recurrence after surgery. To develop new therapeutic strategies and improve the management of advanced CRC, a deep understanding of the metastatic process is of utmost importance. In recent decades, we have learnt that the tumour microenvironment (TME) plays a central role in every phase of oncogenesis and tumour development. The reciprocal and dynamic communication between cancer cells and resident cells, via both paracrine and physical interactions, determines the clinical behaviour of cancer and can affect patients’ response to therapy to a similar extent as the mutational burden leading to oncogenic pathway activation. The liver stands out as a unique and complex microenvironment, distinctly characterised by its tolerogenic nature. This prevents undesirable and excessive immune responses to the high volume of harmless antigens conveyed …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"47 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899280","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 affects gut immune system of patients with inflammatory bowel diseases by modulating metabolomic profiles and mucosal microbiota","authors":"Eiji Miyauchi, Takashi Taida, Kan Uchiyama, Yumiko Nakanishi, Tamotsu Kato, Shigeo Koido, Nobuo Sasaki, Toshifumi Ohkusa, Nobuhiro Sato, Hiroshi Ohno","doi":"10.1136/gutjnl-2025-334922","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-334922","url":null,"abstract":"Background The aetiology and pathogenesis of IBD are intricate, involving genetic and environmental factors. Notably, cigarette smoking has contrasting effects, being detrimental to Crohn’s disease (CD) and beneficial to UC. However, the mechanisms underlying these opposite effects remain unclear. Objective This study aimed to elucidate the precise mechanisms by which smoking influences IBD pathogenesis, by focusing on the roles of microbiota and metabolomics. Design We analysed the microbiota composition of saliva, faeces and the colonic mucosa, and the faecal metabolite profile of patients with IBD and healthy participants. The effects of smoking-associated bacteria on the gut immune system and colitis were evaluated using gnotobiotic mice and murine models of UC and CD. Results People with UC who smoke showed increased concentrations of short-chain fatty acids and aromatic compounds in the faeces compared with the people who quit smoking. The analysis of the mucosal microbiota revealed that smoking is associated with the increased oral bacteria in the colonic mucosa. Monocolonisation of germ-free mice with Streptococcus mitis , one of the oral bacteria ectopically increased in the colonic mucosa, induced interferon (IFN)-γ-producing T cells in the colon. S. mitis also attenuated inflammation in a murine model of UC but exacerbated it in a CD model. Conclusion We demonstrated that smoking affects the gut immune system by modulating mucosal microbiota. Our findings provide insights into how smoking can have beneficial or detrimental effects on UC or CD, respectively, and may shed light on the reasons why individuals with UC who quit smoking experience disease exacerbation. Data are available in a public, open access repository. The 16S rRNA sequence data and the genome sequence data of Streptococcus rubneriS. mitis have been deposited in the DDBJ under BioProject accession numbers PRJDB35832 and PRJDB35831, respectively.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"31 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899332","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":"Comparative risk of high-risk neoplasia after polypectomy among individuals aged below 50 years versus 50 years and older","authors":"Yufeng Chen, Jean Padilla Aponte, Kai Wang, Mengxi Du, Yujia Lu, Georgios Polychronidis, Mingyang Song","doi":"10.1136/gutjnl-2025-335275","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-335275","url":null,"abstract":"Background Limited evidence supports colonoscopy surveillance practices among individuals aged <50 years. Objective To compare the risk of polyp recurrence and colorectal cancer (CRC) among young and old adults after polypectomy. Design We prospectively examined the risk of metachronous high-risk neoplasia, including high-risk adenoma, high-risk serrated polyp (SP) and CRC, according to index colonoscopy findings among individuals aged <50 years and ≥50 years who had received ≥1 follow-up colonoscopy in the Mass General Brigham Colonoscopy Cohort (2007–2023). We used a multivariable-adjusted Cox proportional hazards model to calculate HRs. Results We identified 37 576 adults without polyps, 26 693 with adenomas and 15 425 with SPs (including 8303 with synchronous adenomas and SPs). Among these 10 977 (29.2%), 3385 (12.7%) and 2659 (17.2%) were diagnosed before age 50 years, respectively. The associations between index polyp findings and subsequent risk of high-risk neoplasia were stronger for age <50 years than ≥50 years; however, such differences disappeared (Pheterogeneity>0.05) once the analysis was restricted to index colonoscopy for screening purposes only. Among screened individuals, in both age groups, the association was particularly strong for individuals with index high-risk lesions and peaked at 3 years after polypectomy, with HRs (95% CI) of 4.60 (3.63 to 5.84) and 5.59 (3.89 to 8.03) for young adults with index high-risk adenoma and high-risk SPs, respectively. Conclusion Patients undergoing polypectomy at a screening colonoscopy below age 50 years exhibited a similarly increased risk of metachronous neoplasia as those aged ≥50 years, suggesting that current surveillance guidelines developed in old adults may apply to young adults. Data may be obtained from a third party and are not publicly available. The electronic health record data used for this study are under license to the hospital system and cannot be made publicly available.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"15 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899283","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":"Reassessing the prophylactic effect of clip closure to prevent delayed rebleeding after colorectal endoscopic submucosal dissection","authors":"Uayporn Kaosombatwattana, Suchanart Jitrukthai","doi":"10.1136/gutjnl-2025-336425","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-336425","url":null,"abstract":"We read with great interest the recent EPOC trial by Miyakawa et al , published in Gut , investigating the efficacy of prophylactic clip closure following colorectal endoscopic submucosal dissection (ESD). The authors deserve recognition and appreciation for conducting a well-designed, multicentre randomised controlled trial (RCT) that focused on clinically meaningful endpoints and included a robust per-protocol analysis. Notably, this study addresses a significant gap in the literature by setting delayed bleeding as the primary outcome, which distinguishes it from prior trials where bleeding was only a secondary endpoint. The findings provide valuable evidence supporting the role of prophylactic clip closure in enhancing post-ESD outcomes. While the study undoubtedly holds considerable value, we wish to respectfully raise several concerns regarding the interpretation and generalisability of the findings, particularly concerning the reported incidence of delayed bleeding. The reported absolute delayed …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"27 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899325","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":"Prevalence of serum HBsAg <100 IU/mL in inactive chronic hepatitis B","authors":"Tao Fan, Jian Wang, Chuanwu Zhu, Chao Wu, Rui Huang","doi":"10.1136/gutjnl-2025-336520","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-336520","url":null,"abstract":"Serum hepatitis B surface antigen (HBsAg) levels <100 IU/mL have been proposed as one of the key criteria for the partial cure of chronic HBV infection, which is regarded as a more feasible clinical endpoint for the treatment of chronic hepatitis B (CHB).1 In a recent study by Tseng et al , which explored the association between serum HBsAg levels and hepatocellular carcinoma (HCC) risk in patients with inactive CHB, the importance of serum HBsAg in predicting long-term HCC risk in this population was highlighted.2 During a follow-up period of over 25 years, patients with inactive CHB with serum HBsAg levels <100 IU/mL were found to have a negligible risk of HCC and may not require routine HCC surveillance.2 This study provides important evidence for optimising HCC surveillance strategies in CHB management. Although the study underscores the significance of serum HBsAg <100 IU/mL in predicting HCC risk among patients with inactive CHB, data on the prevalence of such low HBsAg levels in this population remain limited. Therefore, to address this gap, we analysed data from a large, multicentre real-world cohort to determine the proportion and clinical characteristics of treatment-naïve …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"196 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899285","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":"CAF-macrophage crosstalk fuels immunotherapy resistance","authors":"Yang Liu, Linghua Wang","doi":"10.1136/gutjnl-2024-334233","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334233","url":null,"abstract":"Gastric cancer peritoneal metastasis (GCPM) remains a formidable clinical challenge, characterised by poor prognosis and limited therapeutic options. Despite the transformative impact of immune checkpoint blockade (ICB) therapy across various cancer types, its efficacy in GCPM remains restricted, primarily due to profoundly immunosuppressive mechanisms within the tumour microenvironment (TME).1 2 Li et al recently conducted a single-cell transcriptomic analysis of tumour samples from a phase II trial evaluating ICB (sintilimab) combined with chemotherapy in patients with GCPM.2 Their study established a comprehensive single-cell transcriptional atlas, revealing a novel mechanism driving ICB resistance.2 They identified a unique stroma–myeloid niche dominated by THBS2+ matrix cancer-associated fibroblasts (mCAFs) and SPP1+ tumour-associated macrophages (TAMs), within resistant tumours, forming an immunosuppressive hub mediated via complement signalling.2 Specifically, THBS2+ mCAFs secreted complement component C3, engaging its receptor, C3aR (encoded by C3AR1 ) on macrophages. This C3–C3aR signalling drove the recruitment of peritoneal cavity-resident macrophages and their differentiation into SPP1+ TAMs within the tumour niche.2 These infiltrating SPP1+ TAMs correlated with local T cell dysfunction and low natural killer (NK) cell infiltration. Notably, disrupting the CAF-TAM axis in vivo using a C3aR antagonist (SB290157) increased CD8+ T cell infiltration and significantly enhanced anti-programmed cell death protein-1 (PD-1) responses compared with anti-PD-1 alone.2 These findings provide proof of concept that targeting the complement-driven CAF-macrophage crosstalk can remodel the TME and overcome ICB resistance. The insights from Li et al align with the broader understanding that successful immunotherapy often hinges on the state of the TME, with CAFs and TAMs as principal architects of immunosuppressive or immune-excluded environments. Beyond gastric cancer, numerous studies have …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"15 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899319","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}