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IF 29.4 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gastroenterology

Pub Date : 2026-02-11 DOI: 10.1053/j.gastro.2026.02.002

Scott Silvey, Patrick S. Kamath, Jasmohan S. Bajaj

No Abstract

没有抽象的

引用次数: 0

Involvement of Eosinophil-Driven Intestinal Immune Activation in Different Irritable Bowel Syndrome Subtypes and in the Response to a FODMAP Lowering Diet: A Post Hoc Analysis of the Randomized Controlled DOMINO Trial. 嗜酸性粒细胞驱动的肠道免疫激活参与不同肠易激综合征亚型和对FODMAP降低饮食的反应：随机对照DOMINO试验的事后分析

IF 25.1 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gastroenterology

Pub Date : 2026-02-11 DOI: 10.1053/j.gastro.2025.10.021

Karen Routhiaux, Lukas Michaja Balsiger, Matthias Ceulemans, Tim Vanuytsel, Jan Tack, Karen Van Den Houte

引用次数: 0

Enhancing Inpatient Mortality Prognostication in Cirrhosis Patients Through Machine Learning Techniques 通过机器学习技术提高肝硬化患者住院死亡率预测

IF 29.4 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gastroenterology

Pub Date : 2026-02-11 DOI: 10.1053/j.gastro.2025.08.052

Yoshiyasu Takefuji

No Abstract

没有抽象的

引用次数: 0

Quorum sensing molecules are elevated in long-standing ulcerative colitis and are linked to the development of colitis-associated cancer 群体感应分子在长期溃疡性结肠炎中升高，并与结肠炎相关癌症的发展有关

IF 29.4 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gastroenterology

Pub Date : 2026-02-11 DOI: 10.1053/j.gastro.2026.01.023

Gregory O’Connor, Hajar Hazime, Juan F. Burgueño, Irina Fernández, Ana M. Santander, Nivis Brito, Katerina M. Faust, Yuguang Ban, Maria A. Quintero, Sapna K. Deo, Maria T. Abreu, Sylvia Daunert

Background & Aims

Chronic colonic inflammation can lead to colitis-associated cancer (CAC) in ulcerative colitis (UC) patients. The host-microbiome interface plays a critical role in CAC development. Quorum sensing molecules (QSMs) are bacterial products that regulate bacterial processes. We investigated whether QSMs are related to risk factors for CAC in UC patients and drive CAC development in mouse models.

Methods

Blood samples from UC patients and mouse models of CAC (AOM-DSS) were analyzed for three bacterial QSM classes: short-chain (scAHLs) and long-chain n-acyl homoserine lactones (lcAHLs) and autoinducer-2 (AI-2). CAC mouse models (specific pathogen-free and germ-free (GF)) were challenged with C6-scAHL. QSM levels, colitis-associated tumor development, microbiome composition, and metabolome profiles were examined. Murine and human colonic organoid cultures were used to examine C6-scAHL-driven cytokine production.

Results

Serum scAHL levels were higher in UC patients than in healthy controls. UC patients with inflammation and ≥10 years of disease had elevated AI-2 levels. Systemic C6-scAHL administration to a CAC mouse model increased tumor number and size and was associated with microbiome and metabolome changes similar to those in inflammatory settings. C6-scAHL administration also promoted tumor development in GF mice. In colonoids derived from mice and UC patients, C6-scAHL increased tumorigenic and proinflammatory cytokine production.

Conclusions

The bacterial QSM C6-scAHL is elevated in UC patients with CAC risk factors. C6-scAHL promotes colon tumor development in mice and drives pro-inflammatory and pro-tumorigenic cytokine production in vitro. Our findings highlight a previously unexplored pathogenetic pathway linking the microbiome to CAC development and suggest targets to modify CAC risk.

背景：慢性结肠炎症可导致溃疡性结肠炎（UC）患者发生结肠炎相关癌（CAC）。宿主-微生物界面在CAC的发展中起着关键作用。群体感应分子（QSMs）是调节细菌过程的细菌产物。我们研究了QSMs是否与UC患者CAC的危险因素有关，并在小鼠模型中驱动CAC的发展。方法对UC患者和CAC （AOM-DSS）小鼠模型的血液样本进行QSM细菌分类分析：短链（scAHLs）、长链n-酰基同型丝氨酸内酯（lcAHLs）和自诱导物-2 （AI-2）。用C6-scAHL刺激CAC小鼠模型（特异性无病原体和无细菌（GF））。QSM水平、结肠炎相关肿瘤发展、微生物组组成和代谢组谱被检测。小鼠和人类结肠类器官培养用于检测c6 - scahl驱动的细胞因子产生。结果UC患者血清scAHL水平高于健康对照组。伴有炎症且病程≥10年的UC患者AI-2水平升高。CAC小鼠模型全身给予C6-scAHL增加肿瘤数量和大小，并与微生物组和代谢组变化相关，与炎症环境相似。C6-scAHL也促进GF小鼠的肿瘤发展。在小鼠和UC患者的结肠体中，C6-scAHL增加了致瘤性和促炎细胞因子的产生。结论伴有CAC危险因素的UC患者QSM C6-scAHL升高。C6-scAHL促进小鼠结肠肿瘤的发展，并在体外促进促炎和促肿瘤细胞因子的产生。我们的研究结果强调了先前未被探索的将微生物组与CAC发展联系起来的发病途径，并提出了改变CAC风险的靶点。

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引用次数: 0

Genetic Risk of Inflammatory Bowel Disease Is Associated With Disease Course Severity 炎症性肠病的遗传风险与病程严重程度相关

IF 29.4 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gastroenterology

Pub Date : 2026-02-10 DOI: 10.1053/j.gastro.2025.09.018

Marie Vibeke Vestergaard, Kristine Højgaard Allin, Anne Krogh Nøhr, Jesus Vicente Torresano Lominchar, Heidi Søgaard Christensen, Henrik Krarup, Kaspar René Nielsen, Henrik Albæk Jacobsen, Jonas Bybjerg-Grauholm, Marie Bækvad-Hansen, Rasmus Froberg Brøndum, Martin Bøgsted, Lone Larsen, Aleksejs Sazonovs, Tine Jess

Background & Aims

Genetic susceptibility to inflammatory bowel disease (IBD) has been widely studied, whereas the genetic contribution to disease progression remains relatively underinvestigated. In a Danish nationwide cohort, we aimed to explore if genetic susceptibility to IBD associated with disease severity.

Methods

We estimated IBD polygenic scores (PGS) for 3732 patients with Crohn’s disease (CD) and 4535 patients with ulcerative colitis (UC), and investigated their association with disease outcomes, including inflammatory markers, hospitalizations, major surgeries, and medication use. A composite severity outcome was defined based on the 3 years after diagnosis. Lastly, we evaluated disease extent as a possible mediator.

Results

Increased PGS was associated with higher fecal calprotectin and C-reactive protein levels, and decreased hemoglobin levels. When comparing the highest vs lowest PGS quintile, we observed a hazard ratio for major surgery of 2.74 (P = 7.19 × 10⁻¹⁸) in patients with CD and of 2.04 (P = 4.36 × 10⁻⁷) in UC. Patients with severe disease had higher PGS than patients with less severe disease (CD, odds ratio = 1.25; P = 3.36 × 10⁻⁹; UC, odds ratio = 1.33; P = 1.40 × 10⁻¹⁵ per standard deviation increase in PGS). Additionally, PGS was associated with a higher need for corticosteroids, immunomodulators, and biologic therapies. Adjusting for disease extent reduced the estimated associations for CD but had little impact on observed associations for UC.

Conclusions

Patients with higher genetic burden for developing IBD also experience a more severe disease course. For patients with CD this link was largely mediated by disease extent, however, this was not the case for UC, which suggests a shared genetic architecture between disease susceptibility and severity.

背景和目的炎症性肠病（IBD）的遗传易感性已被广泛研究，而遗传对疾病进展的贡献仍相对缺乏研究。在丹麦全国队列中，我们旨在探讨IBD的遗传易感性是否与疾病严重程度相关。方法：我们评估了3732例克罗恩病（CD）患者和4535例溃疡性结肠炎（UC）患者的IBD多基因评分（PGS），并调查了它们与疾病结局的关系，包括炎症标志物、住院、大手术和药物使用。根据诊断后3年确定复合严重程度结局。最后，我们评估了疾病程度作为可能的中介。结果PGS升高与粪钙保护蛋白和c反应蛋白水平升高以及血红蛋白水平降低相关。当比较最高和最低PGS五分位数时，我们观察到CD患者的大手术风险比为2.74 (P = 7.19 × 10−18)，UC患者的风险比为2.04 （P = 4.36 × 10−7）。重症患者的PGS高于轻重症患者（CD，比值比= 1.25;P = 3.36 × 10−9；UC，比值比= 1.33；PGS每标准差增加P = 1.40 × 10−15）。此外，PGS与皮质类固醇、免疫调节剂和生物治疗的更高需求相关。调整疾病程度降低了与CD的估计关联，但对观察到的UC关联影响不大。结论IBD遗传负担越重的患者病程越严重。对于乳糜泻患者，这种联系在很大程度上是由疾病程度介导的，然而，UC的情况并非如此，这表明疾病易感性和严重程度之间存在共同的遗传结构。

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引用次数: 0

Long-Term, Prospective Assessment of Cancer Risk in APC c.3920T>A (I1307K) Carriers: Evidence From a Cohort of Over 21,000 Healthy Individuals. APC c.3920T>A （I1307K）携带者患癌风险的长期、前瞻性评估：来自21,000多名健康个体的证据

IF 25.1 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gastroenterology

Pub Date : 2026-02-10 DOI: 10.1053/j.gastro.2025.10.027

Yael Hoffman, Audelia Eshel Fuhrer, Michal Levy, Diana Kazanov, Nadir Arber, Shiran Shapira

引用次数: 0

Toward Integration of Molecular Measures and Artificial Intelligence-Based Assessments With Clinical End Points in Inflammatory Bowel Disease. 基于炎症性肠病临床终点的分子测量和人工智能评估的整合

IF 25.1 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gastroenterology

Pub Date : 2026-02-10 DOI: 10.1053/j.gastro.2025.12.002

Walter Reinisch, Jens Rittscher, Marietta Iacucci, Simon Travis, Matthias Friedrich

Multimodal profiling of inflammatory bowel disease (IBD) patient tissue and blood samples has revealed the disease spectrum in unprecedented detail, and cellular and molecular correlates of disease severity and outcome in IBD have been elaborated. Incorporating these in the clinical setting would offer a unique opportunity to increase the granularity of current clinical measures and to better assess treatment response. Remission and healing at a cellular/molecular level are also likely to have predictive value for long-term outcomes. Here, we outline a path forward to implementing the most promising molecular disease descriptors as future clinical treatment targets in IBD. We focus on the concept of cellular/molecular measures of inflammation, remission, healing, response to therapy, and target pathway engagement. Monitoring mode-of-action-specific pharmacodynamic modules in the context of disease-related resolution pathways will guide assessment of novel and existing therapies. Artificial intelligence-assisted tools will be key to enabling this development, improving reproducibility, limiting costs, and delivering fast detection.

炎症性肠病（IBD）患者组织和血液样本的多模式分析以前所未有的细节揭示了疾病谱系，并且详细阐述了IBD疾病严重程度和结果的细胞和分子相关性。将这些纳入临床环境将提供一个独特的机会来增加当前临床措施的粒度，并更好地评估治疗反应。细胞/分子水平的缓解和愈合也可能对长期预后具有预测价值。在这里，我们概述了实施最有希望的分子疾病描述符作为IBD未来临床治疗靶点的途径。我们关注炎症、缓解、愈合、治疗反应和靶标通路参与的细胞/分子测量概念。在疾病相关解决途径的背景下监测特定作用模式的药效学模块将指导评估新的和现有的治疗方法。人工智能辅助工具将是实现这一发展、提高可重复性、限制成本和提供快速检测的关键。

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引用次数: 0

Time-Restricted Feeding Reduces Body Mass Index, Visceral Adiposity, Systemic Inflammation, and Clinical Disease Activity in Adults With Crohn's Disease: A Randomized Controlled Study. 一项随机对照研究：限时喂养降低克罗恩病成人体重指数、内脏脂肪、全身炎症和临床疾病活动性

IF 25.1 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gastroenterology

Pub Date : 2026-02-09 DOI: 10.1053/j.gastro.2025.11.008

Natasha Haskey, Jiayu Ye, Ayva Lewis, Munazza Yousuf, Raylene A Reimer, Maitreyi Raman

引用次数: 0

Genomic Insights Into Inflammatory Bowel Disease in United States Hispanic Participants: An Ancestry-Focused Study. 美国西班牙裔参与者炎症性肠病的基因组洞察：一项以血统为重点的研究。

IF 25.1 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gastroenterology

Pub Date : 2026-02-09 DOI: 10.1053/j.gastro.2025.11.007

Ashley H Beecham, Dermot P B McGovern, Steven W Brugger, Mary F Davis, Esther A Torres, Lissette Gomez, Dalin Li, Paola Lopez-Marte, Mark J Daly, Christine Stevens, Shaohong Yang, Sweta Sinha, Emebet Mengesha, James Leavitt, Oriana M Damas, Maria A Quintero, Stephan R Targan, Shervin Rabizadeh, Ksenija Sabic, Judy H Cho, Maria T Abreu, Jacob L McCauley, Talin Haritunians

Background & aims: Genetic admixture of United States Hispanic individuals provides a unique opportunity to examine ancestral origins of inflammatory bowel disease (IBD) risk. In ∼7.3K Hispanic participants (1660 IBD cases; 5614 controls), we examined ancestral heterogeneity of IBD clinical phenotypes and sought to identify IBD risk loci that displayed heterogeneity of effect or were ancestry-specific.

Methods: Association of genetic ancestry with clinical phenotypes was evaluated. We conducted an ancestry-informed genome-wide (GW) association study for IBD, ulcerative colitis, and Crohn's disease (CD) to obtain ancestry-specific effect size estimates for alleles from African (AFR), European (EUR), and Amerindian (AIAN) origin. Ancestry-specific replication was assessed in All of Us Hispanic participants and transferability was evaluated for populations with similar ancestral origin.

Results: Clinical phenotypes were associated with higher AFR (colonic, penetrating, or perianal CD; later age at diagnosis; IBD-related surgery) or AIAN ancestry (colonic CD). GW EUR-specific associations were observed within established loci for CD (NOD2, IL23R, HLA-DRA) and ulcerative colitis (HLA locus). For AFR or AIAN alleles, novel GW associations were observed in 14 loci. One AFR-specific IBD GW (PCGEM1) and 2 AFR-specific suggestive (TYROBP/LRFN3) associations replicated in All of Us. Several suggestive associations demonstrated transferability (AFR-specific TYROBP/LRFN3 and AIAN-specific GAD2). Several novel IBD risk variants also demonstrated association with clinical phenotypes.

Conclusions: Ancestry-informed regression enabled identification of novel AFR and AIAN-specific risk alleles, which may also inform observed phenotypic differences. We have shown that some previously identified IBD loci have associations that are EUR-specific. These findings highlight the importance of genetic ancestry for elucidating the biological underpinnings of IBD and may have important pharmacogenetic implications.

背景与目的：美国西班牙裔个体的遗传混合为研究炎症性肠病（IBD）风险的祖先起源提供了独特的机会。在约7.3万西班牙裔参与者（1660例IBD病例；5614例对照）中，我们检查了IBD临床表型的祖先异质性，并试图确定IBD风险位点，这些位点显示出影响的异质性或具有祖先特异性。方法：评估遗传祖先与临床表型的关系。我们对IBD、溃疡性结肠炎和克罗恩病（CD）进行了一项家谱信息全基因组（GW）关联研究，以获得来自非洲（AFR）、欧洲（EUR）和美洲印第安（AIAN）的等位基因的家谱特异性效应大小估计。我们评估了所有美国西班牙裔参与者的血统特异性复制，并评估了具有相似祖先起源的人群的可转移性。结果：临床表型与较高的AFR（结肠、穿透性或肛周CD；诊断年龄较晚；ibd相关手术）或AIAN血统（结肠CD）相关。在已建立的cd2 （NOD2, IL23R, HLA- dra）和溃疡性结肠炎（HLA位点）的基因座中观察到GW eur特异性关联。对于AFR或AIAN等位基因，在14个位点上观察到新的GW关联。1个afr特异性IBD GW （PCGEM1）和2个afr特异性暗示性关联（TYROBP/LRFN3）在我们所有人中复制。一些暗示的关联显示了可转移性（afr特异性TYROBP/LRFN3和aian特异性GAD2）。一些新的IBD风险变异也被证明与临床表型相关。结论：基于血统的回归能够鉴定出新的AFR和aian特异性风险等位基因，这也可能为观察到的表型差异提供信息。我们已经证明，一些先前确定的IBD基因座与eur特异性相关。这些发现强调了遗传祖先对阐明IBD生物学基础的重要性，并可能具有重要的药理学意义。

{"title":"Genomic Insights Into Inflammatory Bowel Disease in United States Hispanic Participants: An Ancestry-Focused Study.","authors":"Ashley H Beecham, Dermot P B McGovern, Steven W Brugger, Mary F Davis, Esther A Torres, Lissette Gomez, Dalin Li, Paola Lopez-Marte, Mark J Daly, Christine Stevens, Shaohong Yang, Sweta Sinha, Emebet Mengesha, James Leavitt, Oriana M Damas, Maria A Quintero, Stephan R Targan, Shervin Rabizadeh, Ksenija Sabic, Judy H Cho, Maria T Abreu, Jacob L McCauley, Talin Haritunians","doi":"10.1053/j.gastro.2025.11.007","DOIUrl":"https://doi.org/10.1053/j.gastro.2025.11.007","url":null,"abstract":"<p><strong>Background & aims: </strong>Genetic admixture of United States Hispanic individuals provides a unique opportunity to examine ancestral origins of inflammatory bowel disease (IBD) risk. In ∼7.3K Hispanic participants (1660 IBD cases; 5614 controls), we examined ancestral heterogeneity of IBD clinical phenotypes and sought to identify IBD risk loci that displayed heterogeneity of effect or were ancestry-specific.</p><p><strong>Methods: </strong>Association of genetic ancestry with clinical phenotypes was evaluated. We conducted an ancestry-informed genome-wide (GW) association study for IBD, ulcerative colitis, and Crohn's disease (CD) to obtain ancestry-specific effect size estimates for alleles from African (AFR), European (EUR), and Amerindian (AIAN) origin. Ancestry-specific replication was assessed in All of Us Hispanic participants and transferability was evaluated for populations with similar ancestral origin.</p><p><strong>Results: </strong>Clinical phenotypes were associated with higher AFR (colonic, penetrating, or perianal CD; later age at diagnosis; IBD-related surgery) or AIAN ancestry (colonic CD). GW EUR-specific associations were observed within established loci for CD (NOD2, IL23R, HLA-DRA) and ulcerative colitis (HLA locus). For AFR or AIAN alleles, novel GW associations were observed in 14 loci. One AFR-specific IBD GW (PCGEM1) and 2 AFR-specific suggestive (TYROBP/LRFN3) associations replicated in All of Us. Several suggestive associations demonstrated transferability (AFR-specific TYROBP/LRFN3 and AIAN-specific GAD2). Several novel IBD risk variants also demonstrated association with clinical phenotypes.</p><p><strong>Conclusions: </strong>Ancestry-informed regression enabled identification of novel AFR and AIAN-specific risk alleles, which may also inform observed phenotypic differences. We have shown that some previously identified IBD loci have associations that are EUR-specific. These findings highlight the importance of genetic ancestry for elucidating the biological underpinnings of IBD and may have important pharmacogenetic implications.</p>","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":" ","pages":""},"PeriodicalIF":25.1,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141973","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}

引用次数: 0

Defying GRAVITI – Reporting safety data in treat-through studies with rescue mechanisms 对抗地心引力-报告具有救援机制的通过治疗研究的安全性数据

IF 29.4 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gastroenterology

Pub Date : 2026-02-06 DOI: 10.1053/j.gastro.2025.12.037

Jack London, Shahida Din, Alex Bottle, Jonathan Blackwell

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