Pub Date : 2026-02-17DOI: 10.1053/j.gastro.2025.09.043
Yao Zhang, Yanhua Du, Jiaxin Wang, Danshu Wang, Judong Li, Jing Zhang, Yizhou Zhao, Sishen Sun, Hongxiang Sun, Jingjing Qi, Rujuan Bao, Chenghao Shao, Minmin Zhang, Xiangyi He, Ling Zhang, Chunhua Zhou, Dong Wang, Bing Su, Duowu Zou, Youqiong Ye
Unresectable advanced pancreatic ductal adenocarcinoma (PDAC) typically requires systematic chemotherapy, but it remains unclear how this treatment remodels tumor cell plasticity and the tumor microenvironment (TME) to influence clinical outcomes.
Pub Date : 2026-02-17DOI: 10.1053/j.gastro.2026.01.036
Carlo Di Lorenzo, Miguel Saps, Bruno P Chumpitazi, Shaman Rajindrajith, Annamaria Staiano, Nikhil Thapar, Miranda van Tilburg, Carlos Velasco-Benítez, Arine Vlieger
Rome V provides updated criteria for pediatric disorders of gut-brain interaction (DGBI), replacing age-based subdivisions with a classification based on regions and symptom patterns: abdominal pain disorders, defecation and anorectal disorders, and discomfort disorders. New entities were introduced including biliary pain syndrome, centrally mediated abdominal pain syndrome, functional abdominal bloating, and proctalgia fugax. The term "infantile colic" has been replaced with "infant distress syndrome." Existing criteria for irritable bowel syndrome, functional constipation, and nonretentive fecal incontinence were revised to improve diagnostic clarity and reflect current clinical understanding. Rome V also acknowledges that DGBIs may coexist with other conditions producing gastrointestinal symptoms. These updates are intended to support a more consistent diagnostic framework and guide appropriate management strategies for children and adolescents.
{"title":"Lower and Biliary Disorders of Gut-Brain Interaction: Child/Adolescent.","authors":"Carlo Di Lorenzo, Miguel Saps, Bruno P Chumpitazi, Shaman Rajindrajith, Annamaria Staiano, Nikhil Thapar, Miranda van Tilburg, Carlos Velasco-Benítez, Arine Vlieger","doi":"10.1053/j.gastro.2026.01.036","DOIUrl":"https://doi.org/10.1053/j.gastro.2026.01.036","url":null,"abstract":"<p><p>Rome V provides updated criteria for pediatric disorders of gut-brain interaction (DGBI), replacing age-based subdivisions with a classification based on regions and symptom patterns: abdominal pain disorders, defecation and anorectal disorders, and discomfort disorders. New entities were introduced including biliary pain syndrome, centrally mediated abdominal pain syndrome, functional abdominal bloating, and proctalgia fugax. The term \"infantile colic\" has been replaced with \"infant distress syndrome.\" Existing criteria for irritable bowel syndrome, functional constipation, and nonretentive fecal incontinence were revised to improve diagnostic clarity and reflect current clinical understanding. Rome V also acknowledges that DGBIs may coexist with other conditions producing gastrointestinal symptoms. These updates are intended to support a more consistent diagnostic framework and guide appropriate management strategies for children and adolescents.</p>","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":" ","pages":""},"PeriodicalIF":25.1,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146226512","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 : 2026-02-14DOI: 10.1053/j.gastro.2026.02.015
Madhusudan Grover, Giovanni Barbara, William Chey, Bruno P Chumpitazi, Christine Feinle-Bisset, Harriett Schellekens, Eamonn M M Quigley
The past decade has witnessed a tremendous profusion of data on the luminal contents of the gastrointestinal tract and their interactions with the host, many of which have been implicated in the pathophysiology of Disorders of Gut-Brain Interaction (DGBI). The role of food in DGBI-related symptoms has attracted much attention and while many alterations in gut microbiome composition have been described, the multitude of factors that confound study design and interpretation in DGBI has precluded the discovery of a specific microbial "signature". The complexities of the gut barrier, its immune and enteroendocrine systems, so critical to the transmission of signals from lumen to host, continue to be revealed. Along the way, concepts such as the microbiome-gut-brain axis have emerged to explain symptom generation in DGBI, forming the basis for novel diagnostic approaches and therapeutic interventions. Taken together, recent research findings have renewed interest in luminal and enteric phenomena in DGBI.
{"title":"The Intestinal microenvironment and Disorders of Gut-Brain Interactions.","authors":"Madhusudan Grover, Giovanni Barbara, William Chey, Bruno P Chumpitazi, Christine Feinle-Bisset, Harriett Schellekens, Eamonn M M Quigley","doi":"10.1053/j.gastro.2026.02.015","DOIUrl":"https://doi.org/10.1053/j.gastro.2026.02.015","url":null,"abstract":"<p><p>The past decade has witnessed a tremendous profusion of data on the luminal contents of the gastrointestinal tract and their interactions with the host, many of which have been implicated in the pathophysiology of Disorders of Gut-Brain Interaction (DGBI). The role of food in DGBI-related symptoms has attracted much attention and while many alterations in gut microbiome composition have been described, the multitude of factors that confound study design and interpretation in DGBI has precluded the discovery of a specific microbial \"signature\". The complexities of the gut barrier, its immune and enteroendocrine systems, so critical to the transmission of signals from lumen to host, continue to be revealed. Along the way, concepts such as the microbiome-gut-brain axis have emerged to explain symptom generation in DGBI, forming the basis for novel diagnostic approaches and therapeutic interventions. Taken together, recent research findings have renewed interest in luminal and enteric phenomena in DGBI.</p>","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":" ","pages":""},"PeriodicalIF":25.1,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146206651","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 : 2026-02-13DOI: 10.1053/j.gastro.2025.12.038
Shin Fukudo, Qasim Aziz, Douglas A. Drossman, Lukas Van Oudenhove, Adam D. Farmer, Asbjørn M. Drewes, Eva Szigethy
We identify three centrally mediated disorders of gastrointestinal pain in the context of epidemiology, pathophysiology, clinical evaluation and treatment, including pharmacotherapy, brain-gut behavioral therapy and neuromodulation, with emphasis on the importance of a physician-patient relationship. Centrally mediated abdominal pain syndrome is characterized by chronic continuous abdominal pain. It has two main categories: Category A, where the pain occurs without association with physiological events, while in Category B, there is a variable association of pain with physiological events. It is thought to be predominantly a result of central sensitization with altered processing of visceral pain by spinal and brain networks rather than heightened peripheral afferent nerve excitability. Abdominal migraine is newly recognized in adults with paroxysmal, stereotypical episodes of intense abdominal pain. Narcotic bowel syndrome/opioid-induced gastrointestinal hyperalgesia is characterized by the paradoxical development of, or increases in, abdominal pain associated with continuous or increasing dosages of opioids.
{"title":"Centrally Mediated Disorders of Gastrointestinal Pain","authors":"Shin Fukudo, Qasim Aziz, Douglas A. Drossman, Lukas Van Oudenhove, Adam D. Farmer, Asbjørn M. Drewes, Eva Szigethy","doi":"10.1053/j.gastro.2025.12.038","DOIUrl":"https://doi.org/10.1053/j.gastro.2025.12.038","url":null,"abstract":"We identify three centrally mediated disorders of gastrointestinal pain in the context of epidemiology, pathophysiology, clinical evaluation and treatment, including pharmacotherapy, brain-gut behavioral therapy and neuromodulation, with emphasis on the importance of a physician-patient relationship. Centrally mediated abdominal pain syndrome is characterized by chronic continuous abdominal pain. It has two main categories: Category A, where the pain occurs without association with physiological events, while in Category B, there is a variable association of pain with physiological events. It is thought to be predominantly a result of central sensitization with altered processing of visceral pain by spinal and brain networks rather than heightened peripheral afferent nerve excitability. Abdominal migraine is newly recognized in adults with paroxysmal, stereotypical episodes of intense abdominal pain. Narcotic bowel syndrome/opioid-induced gastrointestinal hyperalgesia is characterized by the paradoxical development of, or increases in, abdominal pain associated with continuous or increasing dosages of opioids.","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"8 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146198462","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 : 2026-02-13DOI: 10.1053/j.gastro.2026.01.031
Ignazio Piseddu, Rebekka Endres, Fabian Lanzl, Linda Hammann, Marleen Bérouti, Matthias Thaler, Lisa Fahr, Hannah Fischer, Varvara Varlamova, Jan Gärtig, Daniel Nixdorf, Patrick Layritz, Charlotte Marx, Christine Hörth, Catharina Witte, Alpay Bulut, David Illig, Anne Marie Senz, Lesca Holdt, Ivonne Regel, Veit Hornung
Background & Aims
Chimeric antigen receptor (CAR) T cells have shown great potential in hematological cancers, but lack efficacy in solid tumors, highlighting the need for novel strategies. STING activation was shown to inflame the tumor microenvironment, but combination of STING agonists and CAR-T cells might be limited by detrimental outcomes of T cell-intrinsic STING activation. In this study, we evaluated the potential of combining STING agonists and CAR-T cells in the context of pancreatic cancer
Methods
We assessed the synergy of CRISPR-Cas9-edited CAR-T cells and the STING agonist diABZI within a T cell exhaustion model in vitro and both xenograft and syngeneic mouse models in vivo.
Results
Combination of STING-ablated CAR-T cells and diABZI resulted in enhanced cancer cell killing, increased CAR-T cell proliferation, reduced exhaustion and expansion of an effector-memory phenotype in vitro. Mechanistically, superior CAR-T cell functionality required genetic ablation of STING in CAR-T cells and was dependent on cancer cell-intrinsic STING signaling upon STING-agonistic treatment. Moreover, we identified a synergistic feedback loop comprising the T cell-secreted cytokines IFN-γ and TNF, which prime STING signaling within cancer cells, thereby potentiating the outcomes of cancer cell-intrinsic STING activation in inducing ameliorated CAR-T cell states. Ultimately, we could demonstrate that combination of STINGKO CAR-T cells and diABZI was able to provide enhanced tumor control in both xenograft and syngeneic mouse models. This was accompanied by increased intratumoral CAR-T cell numbers and reprogramming of the tumor microenvironment in vivo.
Conclusion
Our findings suggest that STINGKO CAR-T cells stand to benefit from STING agonists to improve CAR-T cell therapy for immune-deprived cancers such as pancreatic cancer.
{"title":"STING ablation in T cells is required for the efficacy of STING agonists in CAR-T cell immunotherapy of pancreatic cancer.","authors":"Ignazio Piseddu, Rebekka Endres, Fabian Lanzl, Linda Hammann, Marleen Bérouti, Matthias Thaler, Lisa Fahr, Hannah Fischer, Varvara Varlamova, Jan Gärtig, Daniel Nixdorf, Patrick Layritz, Charlotte Marx, Christine Hörth, Catharina Witte, Alpay Bulut, David Illig, Anne Marie Senz, Lesca Holdt, Ivonne Regel, Veit Hornung","doi":"10.1053/j.gastro.2026.01.031","DOIUrl":"https://doi.org/10.1053/j.gastro.2026.01.031","url":null,"abstract":"<h3>Background & Aims</h3>Chimeric antigen receptor (CAR) T cells have shown great potential in hematological cancers, but lack efficacy in solid tumors, highlighting the need for novel strategies. STING activation was shown to inflame the tumor microenvironment, but combination of STING agonists and CAR-T cells might be limited by detrimental outcomes of T cell-intrinsic STING activation. In this study, we evaluated the potential of combining STING agonists and CAR-T cells in the context of pancreatic cancer<h3>Methods</h3>We assessed the synergy of CRISPR-Cas9-edited CAR-T cells and the STING agonist diABZI within a T cell exhaustion model <em>in vitro</em> and both xenograft and syngeneic mouse models <em>in vivo</em>.<h3>Results</h3>Combination of STING-ablated CAR-T cells and diABZI resulted in enhanced cancer cell killing, increased CAR-T cell proliferation, reduced exhaustion and expansion of an effector-memory phenotype <em>in vitro</em>. Mechanistically, superior CAR-T cell functionality required genetic ablation of <em>STING</em> in CAR-T cells and was dependent on cancer cell-intrinsic STING signaling upon STING-agonistic treatment. Moreover, we identified a synergistic feedback loop comprising the T cell-secreted cytokines IFN-γ and TNF, which prime STING signaling within cancer cells, thereby potentiating the outcomes of cancer cell-intrinsic STING activation in inducing ameliorated CAR-T cell states. Ultimately, we could demonstrate that combination of <em>STING</em><sup>KO</sup> CAR-T cells and diABZI was able to provide enhanced tumor control in both xenograft and syngeneic mouse models. This was accompanied by increased intratumoral CAR-T cell numbers and reprogramming of the tumor microenvironment <em>in vivo</em>.<h3>Conclusion</h3>Our findings suggest that <em>STING</em><sup>KO</sup> CAR-T cells stand to benefit from STING agonists to improve CAR-T cell therapy for immune-deprived cancers such as pancreatic cancer.","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"36 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146184272","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 : 2026-02-13DOI: 10.1053/j.gastro.2026.01.033
Elizabeth Barba, Alberto Ezquerra-Durán, Dan Livovsky, Anna Accarino, Fernando Azpiroz
No Abstract
没有抽象的
{"title":"BIOFEEDBACK GUIDED BY THORACOABDOMINAL WALL MOTION FOR THE TREATMENT OF RUMINATION: A RANDOMIZED PLACEBO-CONTROLLED TRIAL","authors":"Elizabeth Barba, Alberto Ezquerra-Durán, Dan Livovsky, Anna Accarino, Fernando Azpiroz","doi":"10.1053/j.gastro.2026.01.033","DOIUrl":"https://doi.org/10.1053/j.gastro.2026.01.033","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"331 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146184273","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 : 2026-02-13DOI: 10.1053/j.gastro.2025.10.022
Asena Pinar Sefer, Baran Erman, Safa Baris, Elif Karakoc-Aydiner, Bernice Lo, Ahmet Ozen
{"title":"Genomic Dissection of Pediatric Protein-Losing Enteropathy and Related Disorders: Clinical, Immunologic, and Therapeutic Insights.","authors":"Asena Pinar Sefer, Baran Erman, Safa Baris, Elif Karakoc-Aydiner, Bernice Lo, Ahmet Ozen","doi":"10.1053/j.gastro.2025.10.022","DOIUrl":"https://doi.org/10.1053/j.gastro.2025.10.022","url":null,"abstract":"","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":" ","pages":""},"PeriodicalIF":25.1,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146179101","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 : 2026-02-12DOI: 10.1053/j.gastro.2026.01.014
Remo Panaccione, Geert R D'haens, Bruce E Sands, John W D Mcdonald, Reena Khanna, Vipul Jairath, Joel G Fletcher, David Bruining, Mark E Baker, Christopher Ma, Florian Rieder, William J Sandborn
{"title":"In Memoriam: Brian G. Feagan, MD, FRCPC (1954-2025).","authors":"Remo Panaccione, Geert R D'haens, Bruce E Sands, John W D Mcdonald, Reena Khanna, Vipul Jairath, Joel G Fletcher, David Bruining, Mark E Baker, Christopher Ma, Florian Rieder, William J Sandborn","doi":"10.1053/j.gastro.2026.01.014","DOIUrl":"https://doi.org/10.1053/j.gastro.2026.01.014","url":null,"abstract":"","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":" ","pages":""},"PeriodicalIF":25.1,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146179029","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 : 2026-02-11DOI: 10.1053/j.gastro.2026.02.002
Scott Silvey, Patrick S. Kamath, Jasmohan S. Bajaj
No Abstract
没有抽象的
{"title":"Reply to Takefuji and Luo","authors":"Scott Silvey, Patrick S. Kamath, Jasmohan S. Bajaj","doi":"10.1053/j.gastro.2026.02.002","DOIUrl":"https://doi.org/10.1053/j.gastro.2026.02.002","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"32 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146153573","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 : 2026-02-11DOI: 10.1053/j.gastro.2025.10.021
Karen Routhiaux, Lukas Michaja Balsiger, Matthias Ceulemans, Tim Vanuytsel, Jan Tack, Karen Van Den Houte
{"title":"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.","authors":"Karen Routhiaux, Lukas Michaja Balsiger, Matthias Ceulemans, Tim Vanuytsel, Jan Tack, Karen Van Den Houte","doi":"10.1053/j.gastro.2025.10.021","DOIUrl":"https://doi.org/10.1053/j.gastro.2025.10.021","url":null,"abstract":"","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":" ","pages":""},"PeriodicalIF":25.1,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156894","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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