Gut最新文献

英文中文

Correction: Prevalence of irritable bowel syndrome and functional dyspepsia after acute gastroenteritis: systematic review and meta-analysis 修正：急性胃肠炎后肠易激综合征和功能性消化不良的患病率：系统回顾和荟萃分析

IF 24.5 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gut

Pub Date : 2025-02-01 DOI: 10.1136/gutjnl-2023-331835corr1

BMJ Publishing Group Ltd and British Society of Gastroenterology

Porcari S, Ingrosso MR, Maida M, et al …

Porcari S, Ingrosso MR， Maida M等。

引用次数: 0

Predictors of response to low-dose amitriptyline for irritable bowel syndrome and efficacy and tolerability according to subtype: post hoc analyses from the ATLANTIS trial

IF 24.5 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gut

Pub Date : 2025-01-25 DOI: 10.1136/gutjnl-2024-334490

Alexandra Wright-Hughes, Pei-Loo Ow, Sarah L Alderson, Matthew J Ridd, Robbie Foy, Felicity L Bishop, Matthew Chaddock, Catherine Fernandez, Elspeth A Guthrie, Delia P Muir, Christopher A Taylor, Amanda J Farrin, Hazel A Everitt, Alexander C Ford

Background Low-dose amitriptyline, a tricyclic antidepressant (TCA), was superior to placebo for irritable bowel syndrome (IBS) in the AmitripTyline at Low-dose ANd Titrated for Irritable bowel syndrome as Second-line treatment (ATLANTIS) trial. Objective To perform post hoc analyses of ATLANTIS for predictors of response to, and tolerability of, a TCA. Design ATLANTIS randomised 463 adults with IBS to amitriptyline (232) or placebo (231). We examined the effect of baseline demographic and disease-related patient characteristics on response to amitriptyline and the effect of amitriptyline on individual symptoms and side effects by subtype. Results There was a quantitative difference in amitriptyline effectiveness in those ≥50 years vs <50 on the IBS severity scoring system (IBS-SSS) (interaction p=0.048, mean difference in ≥50 years subgroup −46.5; 95% CI −74.2 to −18.8, p=0.0010), and subjective global assessment of relief (interaction p=0.068, OR in ≥50 years subgroup 2.59; 95% CI 1.47 to 4.55, p=0.0010), and those in the 70% most deprived areas of England compared with the 30% least deprived for a ≥30% improvement in abdominal pain (interaction p=0.021, OR in 70% most deprived subgroup 2.70; 95% CI 1.52 to 4.77, p=0.0007). Stronger treatment effects were seen in men, with higher Patient Health Questionnaire-12 scores, and with IBS with diarrhoea. Mean differences in individual IBS-SSS components favoured amitriptyline, and side effects were similar, across almost all IBS subtypes. Conclusion These exploratory analyses demonstrate there are unlikely to be deleterious effects of amitriptyline in any particular IBS subtype and could help identify patients in whom amitriptyline may be more effective. Trial registration number [ISRCTN48075063][1]. Data are available on reasonable request. All data requests should be submitted to the corresponding author, ACF, for consideration and would be subject to review by a subgroup of the trial team, which will include the data guarantor, AJF. Access to anonymised data may be granted following this review. All data-sharing activities would require a data-sharing agreement. [1]: /external-ref?link_type=ISRCTN&access_num=ISRCTN48075063

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引用次数: 0

Metabolic dysfunction-associated steatotic liver disease in children

IF 24.5 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gut

Pub Date : 2025-01-23 DOI: 10.1136/gutjnl-2023-331090

Nidhi P Goyal, Stavra Xanthakos, Jeffrey B Schwimmer

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, is the most common cause of chronic liver disease in children. MASLD encompasses a spectrum of liver disease and can be severe, with 10% of affected children presenting with advanced fibrosis. While biopsy remains the most accurate method for diagnosing and staging the disease, MRI proton density fat fraction and magnetic resonance elastography are the most reliable non-invasive measures for assessing steatosis and fibrosis, respectively. MASLD is associated with multiple comorbidities including type 2 diabetes, hypertension, dyslipidaemia, decreased bone mineral density, obstructive sleep apnoea, anxiety and depression. Currently, there are no pharmacological treatments available for children, highlighting the urgent need for paediatric clinical trials. A diet low in free sugars is promising for reducing steatosis and decreasing alanine aminotransferase, a surrogate marker for hepatic inflammation. Emerging data indicate that steatosis can be present in children under 6 years of age, which was previously considered rare. The intricate interplay of genetics may inform future therapeutics and prognostication, with the PNPLA3 gene showing the most evidence for association with the risk and severity of steatotic liver disease and steatohepatitis. MASLD is a complex disease affecting one in ten children and is associated with increased early mortality risk. More dedicated studies are needed in children to advance our understanding of this disease and find effective treatments.

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引用次数: 0

An unusual cause of oesophageal stricture 食管狭窄的不寻常原因

IF 24.5 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gut

Pub Date : 2025-01-22 DOI: 10.1136/gutjnl-2025-334729

Ya-Qi Gao, Jian-Chen Fang, Yun Cui, Jing-Yuan Fang, Dan-Feng Sun

A 57-year-old woman presented to the Gastrointestinal Department with recurrent odynophagia and dysphagia for about 5 years. She also reported a 5-year history of oral soreness and multiple chronic oral ulcers, which were empirically diagnosed with lichen planus without biopsy in a local hospital and treated with steroids intermittently. She underwent upper gastrointestinal endoscopy three times during the last 5 years. Each endoscopy revealed mild stricture in the upper oesophagus with erosions or erythema. Histology results showed mainly inflammation. She was treated for Helicobacter pylori eradication and prescribed with proton pump inhibitors, but her symptoms remained. The physical examination was unremarkable except for mild oral erosions. Her skin was intact, without apparent lesions. Upper gastrointestinal endoscopy was performed again in our hospital, which revealed a whitish mucosa with mild stricture in the proximal third of the oesophagus (figure 1A–B). Stripping of …

一位57岁的女性，因反复出现的吞咽困难和吞咽困难而到胃肠科就诊约5年。她还报告了5年口腔疼痛和多重慢性口腔溃疡史，在当地医院未经活检诊断为扁平苔藓，并间歇性使用类固醇治疗。在过去五年中，她接受了三次上消化道内窥镜检查。每次内镜检查均发现食管上部轻度狭窄伴糜烂或红斑。组织学结果以炎症为主。她接受了根除幽门螺杆菌的治疗，并开了质子泵抑制剂，但她的症状仍然存在。体格检查除轻度口腔糜烂外，无明显异常。她的皮肤完好无损，没有明显的损伤。在我院再次行上消化道内镜检查，发现食管近三分之一处黏膜发白，轻度狭窄（图1A-B）。剥离……

引用次数: 0

Unlocking novel T cell-based immunotherapy for hepatocellular carcinoma through neoantigen-driven T cell receptor isolation 通过新抗原驱动的T细胞受体分离解锁新的基于T细胞的肝癌免疫疗法

IF 24.5 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gut

Pub Date : 2025-01-19 DOI: 10.1136/gutjnl-2024-334148

Panagiota Maravelia, Haidong Yao, Curtis Cai, Daniela Nascimento Silva, Jennifer Fransson, Ola B Nilsson, Yong-Chen William Lu, Patrick Micke, Johan Botling, Francesca Gatto, Giulia Rovesti, Mattias Carlsten, Matti Sallberg, Per Stål, Carl Jorns, Marcus Buggert, Anna Pasetto

Background Tumour-infiltrating T cells can mediate both antitumour immunity and promote tumour progression by creating an immunosuppressive environment. This dual role is especially relevant in hepatocellular carcinoma (HCC), characterised by a unique microenvironment and limited success with current immunotherapy. Objective We evaluated T cell responses in patients with advanced HCC by analysing tumours, liver flushes and liver-draining lymph nodes, to understand whether reactive T cell populations could be identified despite the immunosuppressive environment. Design T cells isolated from clinical samples were tested for reactivity against predicted neoantigens. Single-cell RNA sequencing was employed to evaluate the transcriptomic and proteomic profiles of antigen-experienced T cells. Neoantigen-reactive T cells expressing 4-1BB were isolated and characterised through T-cell receptor (TCR)-sequencing. Results Bioinformatic analysis identified 542 candidate neoantigens from seven patients. Of these, 78 neoantigens, along with 11 hotspot targets from HCC driver oncogenes, were selected for ex vivo T cell stimulation. Reactivity was confirmed in co-culture assays for 14 targets, with most reactive T cells derived from liver flushes and lymph nodes. Liver flush-derived T cells exhibited central memory and effector memory CD4+ with cytotoxic effector profiles. In contrast, tissue-resident memory CD4+ and CD8+ T cells with an exhausted profile were primarily identified in the draining lymph nodes. Conclusion These findings offer valuable insights into the functional profiles of neoantigen-reactive T cells within and surrounding the HCC microenvironment. T cells isolated from liver flushes and tumour-draining lymph nodes may serve as a promising source of reactive T cells and TCRs for further use in immunotherapy for HCC. Data are available upon reasonable request. Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as online supplemental material.

肿瘤浸润性T细胞可以通过创造免疫抑制环境来介导抗肿瘤免疫和促进肿瘤进展。这种双重作用与肝细胞癌（HCC）特别相关，其特点是微环境独特，目前免疫治疗的成功率有限。目的通过分析肿瘤、肝脏冲洗和肝引流淋巴结来评估晚期HCC患者的T细胞反应，以了解在免疫抑制环境下是否可以识别反应性T细胞群。从临床样本中分离的T细胞对预测的新抗原进行了反应性测试。单细胞RNA测序用于评估抗原T细胞的转录组学和蛋白质组学特征。分离了表达4-1BB的新抗原反应性T细胞，并通过T细胞受体（TCR）测序对其进行了表征。结果生物信息学分析鉴定出7例患者的542种候选新抗原。其中，78种新抗原和11种来自HCC驱动癌基因的热点靶点被选择用于体外T细胞刺激。共培养试验证实了14个靶点的反应性，其中大多数反应性T细胞来自肝脏冲洗和淋巴结。肝冲洗衍生的T细胞表现出中枢记忆和效应记忆CD4+与细胞毒性效应谱。相比之下，组织常驻记忆CD4+和CD8+ T细胞的耗尽特征主要在引流淋巴结中发现。这些发现为HCC微环境内和周围新抗原反应性T细胞的功能谱提供了有价值的见解。从肝脏冲洗和肿瘤引流淋巴结中分离的T细胞可能作为反应性T细胞和tcr的有希望的来源，进一步用于HCC的免疫治疗。如有合理要求，可提供资料。如有合理要求，可提供资料。所有与研究相关的数据都包含在文章中或作为在线补充材料上传。

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引用次数: 0

Dynamics of the gut microbiome in FAP patients undergoing intensive endoscopic reduction of polyp burden. 接受强化内窥镜息肉切除术的 FAP 患者肠道微生物群的动态变化。

IF 23 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gut

Pub Date : 2025-01-17 DOI: 10.1136/gutjnl-2024-332381

Sayaka Mizutani, Ayako Tamaki, Satoshi Shiba, Felix Salim, Masayoshi Yamada, Hiroyuki Takamaru, Takeshi Nakajima, Naohisa Yoshida, Shoko Ikuta, Tatsuo Yachida, Tatsuhiro Shibata, Tomoyoshi Soga, Yutaka Saito, Shinji Fukuda, Hideki Ishikawa, Takuji Yamada, Shinichi Yachida

引用次数: 0

Artificial intelligence applied to 'omics data in liver disease: towards a personalised approach for diagnosis, prognosis and treatment. 将人工智能应用于肝病中的 "omics "数据：实现个性化诊断、预后和治疗方法。

IF 23 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gut

Pub Date : 2025-01-17 DOI: 10.1136/gutjnl-2023-331740

Soumita Ghosh, Xun Zhao, Mouaid Alim, Michael Brudno, Mamatha Bhat

Advancements in omics technologies and artificial intelligence (AI) methodologies are fuelling our progress towards personalised diagnosis, prognosis and treatment strategies in hepatology. This review provides a comprehensive overview of the current landscape of AI methods used for analysis of omics data in liver diseases. We present an overview of the prevalence of different omics levels across various liver diseases, as well as categorise the AI methodology used across the studies. Specifically, we highlight the predominance of transcriptomic and genomic profiling and the relatively sparse exploration of other levels such as the proteome and methylome, which represent untapped potential for novel insights. Publicly available database initiatives such as The Cancer Genome Atlas and The International Cancer Genome Consortium have paved the way for advancements in the diagnosis and treatment of hepatocellular carcinoma. However, the same availability of large omics datasets remains limited for other liver diseases. Furthermore, the application of sophisticated AI methods to handle the complexities of multiomics datasets requires substantial data to train and validate the models and faces challenges in achieving bias-free results with clinical utility. Strategies to address the paucity of data and capitalise on opportunities are discussed. Given the substantial global burden of chronic liver diseases, it is imperative that multicentre collaborations be established to generate large-scale omics data for early disease recognition and intervention. Exploring advanced AI methods is also necessary to maximise the potential of these datasets and improve early detection and personalised treatment strategies.

omics技术和人工智能（AI）方法的进步推动了我们在肝脏病学的个性化诊断、预后和治疗策略方面取得进展。本综述全面概述了当前用于分析肝病中的全息数据的人工智能方法。我们概述了各种肝病中不同分子水平的流行情况，并对各项研究中使用的人工智能方法进行了分类。具体来说，我们强调了转录组和基因组剖析的主导地位，以及对蛋白质组和甲基组等其他层面相对稀少的探索，而这些层面代表着新见解尚未开发的潜力。癌症基因组图谱》（The Cancer Genome Atlas）和国际癌症基因组联盟（The International Cancer Genome Consortium）等公共数据库计划为肝细胞癌的诊断和治疗铺平了道路。然而，对于其他肝脏疾病来说，大型全息数据集的可用性仍然有限。此外，应用复杂的人工智能方法来处理复杂的多组学数据集需要大量数据来训练和验证模型，在获得无偏差的临床实用结果方面也面临挑战。本文讨论了解决数据匮乏和把握机遇的策略。鉴于慢性肝病给全球带来的沉重负担，当务之急是建立多中心合作，以生成用于早期疾病识别和干预的大规模组学数据。探索先进的人工智能方法也是必要的，这样才能最大限度地发挥这些数据集的潜力，改善早期检测和个性化治疗策略。

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引用次数: 0

Head of pancreas mass with biliary obstruction: an unusual cause. 胰头肿块伴胆道梗阻：一个不寻常的病因。

IF 23 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gut

Pub Date : 2025-01-17 DOI: 10.1136/gutjnl-2024-332268

Raymond Hayler, Colin Tuft, Oliver Fisher

引用次数: 0

Multiomics of the intestine-liver-adipose axis in multiple studies unveils a consistent link of the gut microbiota and the antiviral response with systemic glucose metabolism. 在多项研究中对肠道-肝脏-脂肪轴进行的多组学研究揭示了肠道微生物群和抗病毒反应与全身葡萄糖代谢之间的一致联系。

IF 23 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gut

Pub Date : 2025-01-17 DOI: 10.1136/gutjnl-2024-332602

Anna Castells-Nobau, José Maria Moreno-Navarrete, Lisset de la Vega-Correa, Irene Puig, Massimo Federici, Jiuwen Sun, Remy Burcelin, Laurence Guzylack-Piriou, Pierre Gourdy, Laurent Cazals, María Arnoriaga-Rodríguez, Gema Frühbeck, Luisa Maria Seoane, José López-Miranda, Francisco J Tinahones, Carlos Dieguez, Marc-Emmanuel Dumas, Vicente Pérez-Brocal, Andrés Moya, Nikolaos Perakakis, Geltrude Mingrone, Stefan Bornstein, Jose Ignacio Rodriguez Hermosa, Ernesto Castro, Jose Manuel Fernández-Real, Jordi Mayneris-Perxachs

Background: The microbiota is emerging as a key factor in the predisposition to insulin resistance and obesity.

Objective: To understand the interplay among gut microbiota and insulin sensitivity in multiple tissues.

Design: Integrative multiomics and multitissue approach across six studies, combining euglycaemic clamp measurements (used in four of the six studies) with other measurements of glucose metabolism and insulin resistance (glycated haemoglobin (HbA1c) and fasting glucose).

Results: Several genera and species from the Proteobacteria phylum were consistently negatively associated with insulin sensitivity in four studies (ADIPOINST, n=15; IRONMET, n=121, FLORINASH, n=67 and FLOROMIDIA, n=24). Transcriptomic analysis of the jejunum, ileum and colon revealed T cell-related signatures positively linked to insulin sensitivity. Proteobacteria in the ileum and colon were positively associated with HbA1c but negatively with the number of T cells. Jejunal deoxycholic acid was negatively associated with insulin sensitivity. Transcriptomics of subcutaneous adipose tissue (ADIPOMIT, n=740) and visceral adipose tissue (VAT) (ADIPOINST, n=29) revealed T cell-related signatures linked to HbA1c and insulin sensitivity, respectively. VAT Proteobacteria were negatively associated with insulin sensitivity. Multiomics and multitissue integration in the ADIPOINST and FLORINASH studies linked faecal Proteobacteria with jejunal and liver deoxycholic acid, as well as jejunal, VAT and liver transcriptomic signatures involved in the actin cytoskeleton, insulin and T cell signalling. Fasting glucose was consistently linked to interferon-induced genes and antiviral responses in the intestine and VAT. Studies in Drosophila melanogaster validated these human insulin sensitivity-associated changes.

Conclusion: These data provide comprehensive insights into the microbiome-gut-adipose-liver axis and its impact on systemic insulin action, suggesting potential therapeutic targets.Cite Now.

背景：微生物群正在成为胰岛素抵抗和肥胖症易感性的关键因素：微生物群正在成为导致胰岛素抵抗和肥胖的关键因素：了解肠道微生物群与多种组织的胰岛素敏感性之间的相互作用：设计：在六项研究中采用多组学和多组织综合方法，将优生血糖钳夹测量（六项研究中的四项采用了这种方法）与葡萄糖代谢和胰岛素抵抗的其他测量方法（糖化血红蛋白（HbA1c）和空腹血糖）相结合：结果：在四项研究（ADIPOINST，n=15；IRONMET，n=121；FLORINASH，n=67；FLOROMIDIA，n=24）中，蛋白质细菌门的几个属和种始终与胰岛素敏感性呈负相关。空肠、回肠和结肠的转录组分析显示，T 细胞相关特征与胰岛素敏感性呈正相关。回肠和结肠中的蛋白质细菌与 HbA1c 呈正相关，但与 T 细胞数量呈负相关。空肠脱氧胆酸与胰岛素敏感性呈负相关。皮下脂肪组织（ADIPOMIT，n=740）和内脏脂肪组织（VAT）（ADIPOINST，n=29）的转录组学揭示了分别与 HbA1c 和胰岛素敏感性相关的 T 细胞相关特征。VAT 蛋白细菌与胰岛素敏感性呈负相关。ADIPOINST 和 FLORINASH 研究中的多组学和多组织整合将粪便蛋白细菌与空肠和肝脏脱氧胆酸以及空肠、VAT 和肝脏转录组特征联系起来，这些特征涉及肌动蛋白细胞骨架、胰岛素和 T 细胞信号传导。空腹血糖与干扰素诱导的基因以及肠道和增值血管中的抗病毒反应密切相关。在黑腹果蝇中进行的研究验证了这些与人类胰岛素敏感性相关的变化：这些数据全面揭示了微生物组-肠道-脂肪肝轴及其对全身胰岛素作用的影响，提出了潜在的治疗目标。

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引用次数: 0

Dysregulated KLF4 expression plays a pivotal role in the pathogenesis of pancreatic intraductal papillary mucinous neoplasms. KLF4 表达失调在胰腺导管内乳头状粘液瘤的发病机制中起着关键作用。

IF 23 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gut

Pub Date : 2025-01-17 DOI: 10.1136/gutjnl-2024-332255

Xiangsheng Zuo, Liang Wang, Yi Liu, Huamin Wang, Margarete Hafley, Mihai Gagea, Ru Chen, Yun Xiong, Sheng Pan, Imad Shureiqi, Robert S Bresalier, Daoyan Wei

引用次数: 0

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