123. Pueraria lobata-derived exosome-like nanovesicles alleviate rheumatoid arthritis via targeting Ruminococcus gnavus phenylethylamine production.
作者: Bingqi Han.;Yutong Jiang.;Haihua Liu.;Fangling Zhang.;Yi Xu.;Zhuang Li.;Songyuan Zheng.;Fopei Ma.;Hao Shi.;Xinlei Jia.;Jinhao Chen.;Leyi Tan.;Huijie Fan.;Shuaijun Lv.;Lei Gao.;Xiaoshan Zhao.;Hong-Wei Zhou.;Juan Li.;Mukeng Hong.
来源: Gut. 2025年
Gut microbiota has been widely recognised as playing a critical role in maintaining immune imbalance and the development of rheumatoid arthritis (RA). As key roles mediating interkingdom crosstalk among plants, microbiomes and mammals, plant-derived exosome-like nanoparticles (ELNs) could use lipids and microRNA components to precisely modulate gene expression of gut microbiota, showing potential as a dietary intervention for RA treatment.
124. Combination therapies for metabolic dysfunction-associated steatohepatitis: challenges and opportunities.
作者: Xiao-Dong Zhou.;Qiong-Yue Fan.;Christopher D Byrne.;Giovanni Targher.;Mark D Muthiah.;Daniel Q Huang.;Qin-Fen Chen.;Mazen Noureddin.;Wenhao Li.;Vlad Ratziu.;Rohit Loomba.;Sven M Francque.;Arun J Sanyal.;Ming-Hua Zheng.
来源: Gut. 2026年75卷4期815-825页
Metabolic dysfunction-associated steatohepatitis (MASH) is a multifactorial metabolic liver disease that occurs in the context of obesity, insulin resistance and cardiometabolic comorbidities. Monotherapy targeting single pathways often provides only partial improvements in histological liver fibrosis and systemic metabolic parameters, prompting growing interest in multitargeted combination therapies. Multitargeted and combination strategies for MASH can modulate multiple and complementary pathogenic processes, potentially improving efficacy, promoting liver fibrosis regression, optimising systemic metabolic outcomes and reducing treatment-related adverse effects. Liver-directed combination therapies, such as thyroid hormone receptor-beta (THR-β) agonists along with acetyl-CoA carboxylase (ACC) inhibitors or peroxisome proliferator-activated receptor agonists, aim to improve histological features of MASH. Regimens combining systemic metabolic and liver-specific agents, such as glucagon-like peptide-1 (GLP-1) receptor agonists with fibroblast growth factor-21 analogues or THR-β agonists, aim to optimise metabolic outcomes, including body weight, insulin resistance and plasma lipids. Thoughtfully designed drug pairings, such as diacylglycerol O-acyltransferase 2 inhibitors combined with ACC inhibitors or GLP-1 and glucagon receptor dual agonists, could improve safety and tolerability by leveraging complementary mechanisms that may mitigate adverse effects. These therapeutic strategies aim to achieve more comprehensive and durable improvements in both liver pathology and systemic health than single-agent therapy alone. This review integrates current knowledge on multitargeted and combination therapies for MASH, examines mechanistic rationales and emerging clinical evidence and addresses practical considerations for patient-centred implementation. Therefore, we aim to provide clinicians and researchers with a comprehensive framework to optimise individualised management and improve both hepatic and systemic outcomes in individuals living with MASH.
125. GSK3βhigh/NFATc1high subtype targeting overcomes therapy resistance in pancreatic cancer through transcriptional induction of homologous recombination repair.
作者: Muhammad Umair Latif.;Xueang Liu.;Aiko Bockelmann.;Laura Huhnold.;Geske Elisabeth Schmidt.;Lukas Klein.;Xueyuan Zhao.;Lena-Christin Conradi.;Karly Conrads.;Anna Lena Weber.;Sercan Mercan.;Kristina Reutlinger.;Atmika Paul.;Zeynab Najafova.;Steven A Johnsen.;Zuriñe Bonilla Del Rio.;Frederike Penz.;Jovan Todorovic.;Holger Bastians.;Tim Beissbarth.;Ulrich Sax.;Ramy Ashry.;Oliver H Krämer.;Elisabeth Hessmann.;Günter Schneider.;Philipp Stroebel.;Ivan Bogeski.;Shiv K Singh.;Volker Ellenrieder.
来源: Gut. 2026年
The efficacy of pharmacological glycogen synthase kinase-3β (GSK3β) inhibition is currently being investigated in unselected cohorts of metastatic pancreatic ductal adenocarcinoma (PDAC). Here, we sought to determine the clinical significance of nuclear GSK3β accumulation in patients with resectable PDAC.
127. TL1A-activated T cells remodel the rectal mucosa in patients with Crohn's disease with perianal fistulising disease.
作者: Victoria Gudiño.;Jae Won Cho.;Berta Caballol.;Ángela Sanzo-Machuca.;Ana Corraliza.;Marisol Veny.;Isabella Dotti.;Livia Moreira Genaro.;Elisa Melón-Ardanaz.;Maria Carme Masamunt.;Miriam Esteller.;Iris Teubel.;Lisseth Robbins.;Àngel Giner.;Cristina Prieto.;Elena Ferrer.;Raquel Franco Leal.;Albert Martin-Cardona.;Carme Loras.;Maria Esteve.;Jordi Rimola.;Agnès Fernández-Clotet.;Ingrid Ordás.;Elena Ricart.;Julian Panés.;Martin Hemberg.;Azucena Salas.
来源: Gut. 2025年
Perianal fistulising disease (PFD) is a complication that affects about 20% of patients with Crohn's disease (CD) whose aetiology remains unknown.
128. Parasutterella excrementihominis exacerbates experimental colitis and colitis-associated colorectal cancer via pathogenic NETosis activation.
作者: Huishi Tan.;Linwen Huang.;Jun Wang.;Hongli Huang.;Zelong Lin.;Siqi Yang.;Yanqiang Shi.;Jierui Li.;Haiyan Zhang.;Yongjian Zhou.;Chongyang Huang.
来源: Gut. 2026年75卷5期920-936页
Parasutterella excrementihominis (P. excrementihominis), a Betaproteobacteria species enriched in ulcerative colitis (UC) patients, is implicated in chronic inflammation. However, its mechanistic role in UC progression and colitis-associated colorectal cancer (CAC) remains unclear.
129. Targeting cancer stem cells enhances multikinase inhibitor therapy in metabolic dysfunction-associated steatotic liver disease-related hepatocellular carcinoma.
作者: Yasi Pan.;Xiang Zhang.;Chi Chun Wong.;Huarong Chen.;Stephanie Ma.;Terence Kin-Wah Lee.;Kai Yuan.;Cong Liang.;Xingyu Zhou.;Harry Cheuk Hay Lau.;Pingmei Huang.;Danyu Chen.;Lina Wang.;Yanqiang Ding.;Qinyao Wei.;Alvin Ho Kwan Cheung.;Ka Fai To.;Jun Yu.
来源: Gut. 2025年
Metabolic dysfunction-associated steatotic liver disease-related hepatocellular carcinoma (MASLD-HCC) is an emerging malignancy with limited therapeutic options. The identity and function of cancer stem cells (CSCs) in MASLD-HCC remain poorly understood. In this study, we characterised CSCs in MASLD-HCC and investigated their contribution to MASLD-HCC tumourigenesis and therapy response.
130. Metabolomic pattern of ultraprocessed food intake and its association with colorectal cancer risk.
作者: Mengxi Du.;Xinyu Wang.;Dong Hang.;Fenglei Wang.;Yujia Lu.;Kai Wang.;Alaina M Bever.;Ana Nogal.;Danielle Haslam.;Shuji Ogino.;Jeffrey A Meyerhardt.;Liming Liang.;Qi Sun.;Curtis Huttenhower.;Andrew T Chan.;Frank B Hu.;Mingyang Song.
来源: Gut. 2025年
High ultra-processed food (UPF) intake has been linked to colorectal cancer (CRC), but underlying mechanisms remain unclear.
131. Global guidelines on diverticular disease of the colon: the Fiesole Consensus report.
作者: Antonio Tursi.;Giovanni Brandimarte.;Francesco Di Mario.;Wenjie Ma.;Juozas Kupcinskas.;Jaroslaw Regula.;Giovanni Maconi.;Peter Malfertheiner.;Giovanni Barbara.;Neil Stollman.;Savvas Papagrigoriadis.;Thomas Golda.;Antonio Amato.;Mauro Bafutto.;Gabrio Bassotti.;Gian A Binda.;Sebastiano Biondo.;Pellegrino Crafa.;Dan Dumitrascu.;Walter Elisei.;Nicola Flor.;Kok Ann Gwee.;David James Humes.;Takaomi Kessoku.;Wolfgang Kruis.;Adi Lahat.;Angel Lanas.;Atsushi Nakajima.;Marcello Picchio.;Robin C Spiller.;Athena Adamopoulos.;Carmelo Scarpignato.
来源: Gut. 2025年
Colonic diverticulosis is the most common structural abnormality of the colon in developed countries, with an increasing global prevalence. Approximately 20-25% of affected individuals develop symptoms, collectively referred to as diverticular disease. Given its wide clinical spectrum, evolving pathophysiological insights and growing disease burden, updated guidance is essential.
133. Twenty-four-week anti-PD-1 antibody regimen promoted HBsAg reduction and concurrently enhanced HBV-specific T cell responses in patients with chronic hepatitis B.
作者: Taiyu He.;Min Chen.;Maoying Liu.;Li Zhang.;Huidan Sun.;Lu Zhang.;Aoyi Li.;Weiqun Zeng.;Ning Ling.;Xiaofeng Shi.;Hua He.;Mingli Peng.;Dachuan Cai.;Peng Hu.;Dazhi Zhang.;Yinghua Lan.;Hong Ren.
来源: Gut. 2025年
PD-1 blockade has emerged as a promising approach for functional cure of chronic hepatitis B (CHB).
134. Comparison between germline and somatic loss-of-function RNF43 mutations reveals different genotype-phenotype associations and provides insights into the genetic mechanisms of colorectal tumourigenesis.
作者: Claire Palles.;Luke Freeman-Mills.;Edward Arbe-Barnes.;Nathalie Feeley.;Laura Chegwidden.;Helen Curley.;Sara Galavotti.;Connor Woolley.;Jeremy Cheadle.;Dmitri Mouradov.;Oliver Sieber.;Silvia Salatino.;Steve Thorn.;Anshita Goel.;Juan Fernandez-Tajes.;Sulochana Omwenga.;Sujata Biswas.;Timothy Maughan.;Simon J Leedham.; .; .; .; .;Viktor Hendrik Koelzer.;Lai Mun Wang.;Roland Arnold.;James Edward East.;Ian Tomlinson.
来源: Gut. 2025年
Germline RNF43 mutations cause a dominantly inherited syndrome of colorectal cancer (CRC) and serrated polyps. However, these data originate from highly selected families.
137. Tracking B cell immunity during perturbation of hepatitis B infection induced by treatment withdrawal.
作者: Sabela Lens.;Alice R Burton.;Jessica Davies.;Maelle Locatelli.;Mireia García-López.;Anna Pocurull.;Anna Jeffery-Smith.;Nikolai Novikov.;Simon P Fletcher.;Xavier Forns.;Sofía Pérez-Del-Pulgar.;Mala K Maini.
来源: Gut. 2025年
Withdrawal of prolonged nucleos(t)ide analogue (NA) treatment results in hepatitis B surface antigen (HBsAg) loss in some subjects with chronic hepatitis B (CHB), potentially revealing immune correlates of functional cure.
138. Circulating HBV RNA and HBsAg seroconversion in patients with chronic HBV infection: a long-term follow-up study starting from childhood in Taiwan.
作者: Jia-Feng Wu.;Chien-Ting Hsu.;Chi-San Tai.;Kai-Chi Chang.;Chieh-Yu Chu.;Yu-Chun Chiu.;Huey-Ling Chen.;Yen-Hsuan Ni.;Mei-Hwei Chang.
来源: Gut. 2025年
HBV surface antigen (HBsAg) seroconversion indicates the clearance of HBV in patients with chronic HBV infection.
140. Hereditary chronic pancreatitis induced plasticity cooperates with mutant Kras in early pancreatic carcinogenesis.
作者: Tanvi Vikrant Inamdar.;Ferdinand Krannich.;Nico Hesselbarth.;Atul Verma.;Teresa Vauti.;Mariami Helena Jasaszwili.;Ghanem El Kassem.;Jasmine Hillmer.;Tom Kaune.;Michael Boettcher.;Ivonne Regel.;Heidi Griesmann.;Irene Esposito.;Markus Glaß.;Monika Hämmerle.;Patrick Michl.;Helmut Laumen.;Jonas Rosendahl.
来源: Gut. 2026年75卷5期1003-1014页
Chronic pancreatitis (CP) is a risk factor for pancreatic cancer, with inherited cases conferring a markedly increased risk. The underlying mechanisms driving malignant transformation by CP remain poorly understood.
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