Pub Date : 2026-03-18DOI: 10.1136/gutjnl-2026-338145
Sepideh Mikaeeli,David E Cohen
{"title":"Targeting lipid droplets in the management of MASLD.","authors":"Sepideh Mikaeeli,David E Cohen","doi":"10.1136/gutjnl-2026-338145","DOIUrl":"https://doi.org/10.1136/gutjnl-2026-338145","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":"19 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147478588","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}
Pub Date : 2026-03-18DOI: 10.1136/gutjnl-2026-338396
Bochen Xiang, Xiangcheng Dai, Xiaolin Zhou
{"title":"Comment on: Therapeutic inhibition of HBsAg and HBV cccDNA through a novel phased combination treatment: glycine and interferon-α.","authors":"Bochen Xiang, Xiangcheng Dai, Xiaolin Zhou","doi":"10.1136/gutjnl-2026-338396","DOIUrl":"https://doi.org/10.1136/gutjnl-2026-338396","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":25.8,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147480548","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}
BACKGROUNDVasculogenic mimicry (VM) is a non-endothelial vascularisation programme sustaining pancreatic ductal adenocarcinoma (PDAC) perfusion and metastasis, yet its regulators and therapeutic vulnerabilities remain unclear.OBJECTIVETo elucidate the immune and epigenetic mechanisms regulating VM and identify strategies to overcome VM-driven PDAC progression.DESIGNHistopathology, three-dimensional tissue clearing, spatial transcriptomics and single-cell RNA sequencing were combined to map VM distribution and its immune contexture. Tissue microarrays, co-culture assays and xenograft models were used to assess tumour-associated macrophage (TAM) contributions. Extracellular vesicle (EV) proteomics and mechanistic studies identified cargo molecules and signalling pathways. DOT1L (disruptor of telomeric silencing 1-like) inhibitor EPZ-5676 and vascular endothelial growth factor receptor (VEGFR) inhibitor axitinib were used for therapeutic validation.RESULTSVM was abundant in PDAC, increased with tumour stage and was preferentially surrounded by TAMs. M2-like TAMs promoted tube formation, invasion and tumour growth, while blockade of TAM-derived EVs abolished these effects. EV proteomics identified caveolin-1 (CAV1) as a key cargo correlating with VM density and TAM infiltration. Mechanistically, EV-delivered CAV1 interacted with DOT1L, promoted DOT1L EV loading and drove H3K79 methylation-dependent autophagy-related 5 (ATG5) transcription, sustaining VM and invasive phenotypes. Notably, while DOT1L inhibition suppressed VM and tumour progression, it paradoxically induced compensatory endothelial angiogenesis. Combined DOT1L and VEGFR blockade overcame this compensatory feedback, achieving superior tumour control without toxicity.CONCLUSIONTAM-derived EVs drive VM through a CAV1-DOT1L-ATG5 axis. We identify a compensatory link between VM and angiogenesis and demonstrate that dual targeting of these two vascular modalities offers a promising therapeutic strategy for PDAC.
{"title":"CAV1-DOT1L axis in TAM-derived EVs orchestrates VM and sensitises PDAC to combined VM and VEGF targeting.","authors":"Ziyu Liu,Ying Zhang,Haonan Wu,Han Liu,Tongjia Chu,Huan Liu,Jian Zhang,Feng Wei","doi":"10.1136/gutjnl-2025-337293","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-337293","url":null,"abstract":"BACKGROUNDVasculogenic mimicry (VM) is a non-endothelial vascularisation programme sustaining pancreatic ductal adenocarcinoma (PDAC) perfusion and metastasis, yet its regulators and therapeutic vulnerabilities remain unclear.OBJECTIVETo elucidate the immune and epigenetic mechanisms regulating VM and identify strategies to overcome VM-driven PDAC progression.DESIGNHistopathology, three-dimensional tissue clearing, spatial transcriptomics and single-cell RNA sequencing were combined to map VM distribution and its immune contexture. Tissue microarrays, co-culture assays and xenograft models were used to assess tumour-associated macrophage (TAM) contributions. Extracellular vesicle (EV) proteomics and mechanistic studies identified cargo molecules and signalling pathways. DOT1L (disruptor of telomeric silencing 1-like) inhibitor EPZ-5676 and vascular endothelial growth factor receptor (VEGFR) inhibitor axitinib were used for therapeutic validation.RESULTSVM was abundant in PDAC, increased with tumour stage and was preferentially surrounded by TAMs. M2-like TAMs promoted tube formation, invasion and tumour growth, while blockade of TAM-derived EVs abolished these effects. EV proteomics identified caveolin-1 (CAV1) as a key cargo correlating with VM density and TAM infiltration. Mechanistically, EV-delivered CAV1 interacted with DOT1L, promoted DOT1L EV loading and drove H3K79 methylation-dependent autophagy-related 5 (ATG5) transcription, sustaining VM and invasive phenotypes. Notably, while DOT1L inhibition suppressed VM and tumour progression, it paradoxically induced compensatory endothelial angiogenesis. Combined DOT1L and VEGFR blockade overcame this compensatory feedback, achieving superior tumour control without toxicity.CONCLUSIONTAM-derived EVs drive VM through a CAV1-DOT1L-ATG5 axis. We identify a compensatory link between VM and angiogenesis and demonstrate that dual targeting of these two vascular modalities offers a promising therapeutic strategy for PDAC.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"34 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483733","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}
Pub Date : 2026-03-18DOI: 10.1136/gutjnl-2026-338333
Jianing Li,Yonghao Chen,Xiaoyin Bai,Yunlu Feng
{"title":"When a pancreatic pseudocyst is not a pseudocyst: diagnostic pitfalls and complications.","authors":"Jianing Li,Yonghao Chen,Xiaoyin Bai,Yunlu Feng","doi":"10.1136/gutjnl-2026-338333","DOIUrl":"https://doi.org/10.1136/gutjnl-2026-338333","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":"7 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147478592","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}
Pub Date : 2026-03-18DOI: 10.1136/gutjnl-2026-338610
Bingtian Dong,Yuping Chen,Xiaolong Qi, ,
{"title":"Response letter to: clarifying decision rules and implementation boundaries for a two-step FIB-4-VCTE pathway in type 2 diabetes and MASLD.","authors":"Bingtian Dong,Yuping Chen,Xiaolong Qi, , ","doi":"10.1136/gutjnl-2026-338610","DOIUrl":"https://doi.org/10.1136/gutjnl-2026-338610","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":"409 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147478590","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}
Pub Date : 2026-03-11DOI: 10.1136/gutjnl-2026-338140
Lucia Parlati,Marc Bourliere
{"title":"Steatosis severity and metabolic fingerprints after HCV eradication: toward an individualised approach to HCC surveillance after HCV cure.","authors":"Lucia Parlati,Marc Bourliere","doi":"10.1136/gutjnl-2026-338140","DOIUrl":"https://doi.org/10.1136/gutjnl-2026-338140","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":"55 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147393827","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}
Pub Date : 2026-03-10DOI: 10.1136/gutjnl-2026-338607
Wojciech Marlicz,Marcin Krawczyk,Piotr Milkiewicz
{"title":"Rifaximin in symptomatic uncomplicated diverticular disease: a stewardship perspective following the Fiesole Consensus.","authors":"Wojciech Marlicz,Marcin Krawczyk,Piotr Milkiewicz","doi":"10.1136/gutjnl-2026-338607","DOIUrl":"https://doi.org/10.1136/gutjnl-2026-338607","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":"14 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147383283","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}
Pub Date : 2026-03-10DOI: 10.1136/gutjnl-2025-336980
Borja Martinez-Tellez, Milena Schönke, Artemiy Kovynev, Esther Garcia-Dominguez, Lourdes Ortiz-Alvarez, Aswin Verhoeven, Ranko Gacesa, Arnau Vich Vila, Quinten Raymond Ducarmon, David Jimenez-Pavon, Maria Del Carmen Gomez-Cabrera, Rinse K Weersma, Wiep-Klaas Smits, Martin Giera, Jonatan R Ruiz, Patrick Cn Rensen
Background: Gut bacteria have been implicated in a wide range of health conditions, yet their potential role in preventing and treating muscle-wasting disorders remains largely unexplored.
Objective: We aimed to investigate whether specific gut microbial species are associated with muscle strength and to explore underlying mechanisms linking the gut microbiota to muscle health.
Design: We conducted metagenomic analyses in cohorts of younger and older adults extensively phenotyped for muscle strength. Associations were tested between bacterial taxa and performance measures. Causality was assessed by oral supplementation of candidate species in antibiotic-treated mice. Metabolomic profiling and muscle phenotyping were performed to elucidate mechanisms.
Results: The relative abundance of Roseburia inulinivorans, but not other Roseburia species, was positively associated with multiple strength measures including handgrip, leg press and bench press in humans. Supplementation of R. inulinivorans in mice significantly enhanced forelimb grip strength, whereas other Roseburia species had no effect. Metabolomic analyses revealed that R. inulinivorans reduced amino acid concentrations in the caecum and plasma, while activating the purine and pentose phosphate pathway in muscle. These changes coincided with increased muscle fibre size and a shift from type I to type II fibres. Accordingly, we observed that the relative abundance of R. inulinivorans is lower in older adults compared with young adults.
Conclusion: R. inulinivorans emerges as a species-specific modulator of muscle strength, linking gut microbiota to muscle metabolism and function. These findings support its potential as a probiotic candidate for nutraceutical interventions targeting age-related muscle-wasting diseases.
{"title":"<i>Roseburia inulinivorans</i> increases muscle strength.","authors":"Borja Martinez-Tellez, Milena Schönke, Artemiy Kovynev, Esther Garcia-Dominguez, Lourdes Ortiz-Alvarez, Aswin Verhoeven, Ranko Gacesa, Arnau Vich Vila, Quinten Raymond Ducarmon, David Jimenez-Pavon, Maria Del Carmen Gomez-Cabrera, Rinse K Weersma, Wiep-Klaas Smits, Martin Giera, Jonatan R Ruiz, Patrick Cn Rensen","doi":"10.1136/gutjnl-2025-336980","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-336980","url":null,"abstract":"<p><strong>Background: </strong>Gut bacteria have been implicated in a wide range of health conditions, yet their potential role in preventing and treating muscle-wasting disorders remains largely unexplored.</p><p><strong>Objective: </strong>We aimed to investigate whether specific gut microbial species are associated with muscle strength and to explore underlying mechanisms linking the gut microbiota to muscle health.</p><p><strong>Design: </strong>We conducted metagenomic analyses in cohorts of younger and older adults extensively phenotyped for muscle strength. Associations were tested between bacterial taxa and performance measures. Causality was assessed by oral supplementation of candidate species in antibiotic-treated mice. Metabolomic profiling and muscle phenotyping were performed to elucidate mechanisms.</p><p><strong>Results: </strong>The relative abundance of <i>Roseburia inulinivorans</i>, but not other <i>Roseburia</i> species, was positively associated with multiple strength measures including handgrip, leg press and bench press in humans. Supplementation of <i>R. inulinivorans</i> in mice significantly enhanced forelimb grip strength, whereas other <i>Roseburia</i> species had no effect. Metabolomic analyses revealed that <i>R. inulinivorans</i> reduced amino acid concentrations in the caecum and plasma, while activating the purine and pentose phosphate pathway in muscle. These changes coincided with increased muscle fibre size and a shift from type I to type II fibres. Accordingly, we observed that the relative abundance of <i>R. inulinivorans</i> is lower in older adults compared with young adults.</p><p><strong>Conclusion: </strong><i>R. inulinivorans</i> emerges as a species-specific modulator of muscle strength, linking gut microbiota to muscle metabolism and function. These findings support its potential as a probiotic candidate for nutraceutical interventions targeting age-related muscle-wasting diseases.</p><p><strong>Trial registration number: </strong>NCT02365129.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":25.8,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147432602","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}
Pub Date : 2026-03-09DOI: 10.1136/gutjnl-2025-337856
Joana Camões Neves,Dalila Costa,Carla Rolanda
{"title":"Appearances can be deceiving: an ulcerated oesophageal lesion.","authors":"Joana Camões Neves,Dalila Costa,Carla Rolanda","doi":"10.1136/gutjnl-2025-337856","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-337856","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":"16 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147381278","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}
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