{"title":"Advancing liver health in a shifting global landscape","authors":"","doi":"10.1038/s41575-026-01228-2","DOIUrl":"10.1038/s41575-026-01228-2","url":null,"abstract":"Global liver health is at a pivotal moment, marked by a rising steatotic liver disease burden alongside stalled progress in viral hepatitis elimination. Strengthening prevention and access to care is essential to reduce inequities, morbidity and mortality worldwide.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 8","pages":"603-603"},"PeriodicalIF":57.5,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41575-026-01228-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The mesenteric model of abdominal anatomy","authors":"J. Calvin Coffey, Dara Walsh, Peter Dockery","doi":"10.1038/s41575-026-01227-3","DOIUrl":"10.1038/s41575-026-01227-3","url":null,"abstract":"The mesenteric model is a new anatomy of the abdomen that defines a mesentery-based organ system unifying structure, development and function, reveals system-level mechanisms of disease, enables targeted therapies, and provides a coherent scientific foundation for integrating biological research with clinical practice across both abdominal and systematic medicine.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 9","pages":"669-670"},"PeriodicalIF":57.5,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148393727","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}
Rachel K. Zwick, Mark Sharpley, Jérémie Rispal, Shervin Rabizadeh, Dario Boffelli, Ophir D. Klein
{"title":"Regional organization of nutrient absorption across the small intestine","authors":"Rachel K. Zwick, Mark Sharpley, Jérémie Rispal, Shervin Rabizadeh, Dario Boffelli, Ophir D. Klein","doi":"10.1038/s41575-026-01225-5","DOIUrl":"10.1038/s41575-026-01225-5","url":null,"abstract":"The small-intestinal epithelium must simultaneously enable functions that are spatially compartmentalized along the length of the organ: nutrient absorption and protection against environmental insults. Although regional differences within the intestine have been recognized for centuries, only now has a comprehensive framework emerged to define this organization at molecular, cellular and functional levels. In this Review, we highlight the epigenetic and transcriptional features of small-intestinal zonation across longitudinal and apical–basal axes, and we examine the molecular mechanisms that establish regional gene expression profiles in epithelial cells during development and that maintain these distinctions into adulthood. We integrate these molecular insights with physiological data to present a refined model of the functional landscape of nutrient absorption. Finally, we discuss gastrointestinal diseases that target specific intestinal regions, underscoring the importance of understanding local tissue environments within this highly regionalized organ. The mammalian small intestine is spatially segregated across its length according to distinct processes and functions, including nutrient absorption and protection against environmental insults such as pathogens. This Review examines the regional organization of the small-intestinal epithelium, highlighting molecular, cellular and functional features during development and disease.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 10","pages":"741-759"},"PeriodicalIF":57.5,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148372541","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}
Markus F. Neurath, Raja Atreya, Jean-Frederic Colombel, Saurabh Mehandru
{"title":"Engineering immune cell therapies for inflammatory bowel disease: from stem cells to CAR T cells","authors":"Markus F. Neurath, Raja Atreya, Jean-Frederic Colombel, Saurabh Mehandru","doi":"10.1038/s41575-026-01226-4","DOIUrl":"10.1038/s41575-026-01226-4","url":null,"abstract":"Despite the development of novel small molecules and antibody-based therapies targeting pro-inflammatory immune pathways, the clinical management of inflammatory bowel disease (IBD) remains challenging. In this Perspective, we highlight emerging treatment strategies with a focus on engineered cellular immunotherapies, including stem cell-based approaches, regulatory T cell and type 1 regulatory T cell therapies, as well as chimeric antigen receptor (CAR) T cell platforms (CAR T cells, CAR Treg cells). Early-stage studies using haematopoietic and mesenchymal stem cells have yielded promising clinical results, although the safety and efficacy of such therapies require further careful validation. Moreover, efforts in immune cell engineering are now directed towards the expansion and adoptive transfer of allogeneic IL-10-producing type 1 regulatory T cells and autologous transforming growth factor-β-secreting regulatory T cells, which are currently being evaluated in early-stage clinical trials. Notably, a recent case report demonstrated that CD19-targeted CAR T cell therapy can induce long-term remission of intestinal inflammation in ulcerative colitis, highlighting a potential pathogenic role of mucosal B cells and plasmablasts in ulcerative colitis and underscoring the transformative therapeutic potential of CAR T cell strategies in IBD. Although these approaches offer exciting therapeutic prospects in IBD, rigorous prospective and controlled clinical trials are essential to fully assess their safety and efficacy. In this Perspective, Neurath and colleagues discuss immune cell therapies for inflammatory bowel disease, including stem cell-based approaches, regulatory T cell therapies and chimeric antigen receptor T cell therapies. They also discuss future directions for research.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 10","pages":"791-801"},"PeriodicalIF":57.5,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148361547","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}
{"title":"Actin cytoskeletal dynamics in hepatic myofibroblasts and fibrosis","authors":"Zengdun Shi, Don C. Rockey","doi":"10.1038/s41575-026-01223-7","DOIUrl":"10.1038/s41575-026-01223-7","url":null,"abstract":"Fibrosis represents a pathological wound-healing response that occurs after nearly any type of organ injury and has been estimated to lead to half of all deaths in the industrialized world. Current evidence indicates that the extracellular matrix in the fibrotic lesion is primarily produced by activated fibroblasts and/or myofibroblasts. In the liver, the key fibrosis effector cell is the hepatic stellate cell (HSC), which undergoes phenotypic switching from a quiescent (normal) state to a hepatic myofibroblast (activated state). The classic signature for the activated HSC is not only upregulation of various extracellular matrix mRNAs and proteins, particularly type 1 collagen, but also the de novo expression of multiple smooth muscle mRNAs and proteins, including the smooth muscle isoform of actin (smooth muscle α-actin), which supports a robust actin cytoskeleton. Growing evidence indicates that the actin cytoskeleton has a critical role in multiple essential HSC activities during the wound-healing response, including cell migration, contraction, signal transduction and matrix gene expression. In this Review, we focus on the role of the actin cytoskeleton and the molecular processes linking this critically important cellular structure to the cell biology of fibrosis. Liver fibrosis drives chronic liver disease and liver cancer. This Review dissects how actin cytoskeleton dynamics and related pathways govern hepatic stellate activation and fibrogenesis with implications for targeted therapy.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 10","pages":"760-775"},"PeriodicalIF":57.5,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148349229","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}
Panagiota Gatoula, Dimitris K. Iakovidis, Dimitrios E. Diamantis, Vajira Thambawita, Thomas de Lange, Anastasios Koulaouzidis
{"title":"Synthetic data generation: challenges and perspectives for gastrointestinal medicine","authors":"Panagiota Gatoula, Dimitris K. Iakovidis, Dimitrios E. Diamantis, Vajira Thambawita, Thomas de Lange, Anastasios Koulaouzidis","doi":"10.1038/s41575-026-01216-6","DOIUrl":"10.1038/s41575-026-01216-6","url":null,"abstract":"In the era of artificial intelligence, machines are demonstrating an unprecedented capacity to learn from massive amounts of real-world data to perform human-like cognitive processes, enabling them to recognize environments, objects, and conditions and make critical decisions more accurately than ever. In the medical field, the potential to generate realistic, privacy-preserving, unbiased synthetic data can be the key to unlocking the potential of artificial intelligence in medicine and overcoming the current barriers such as data privacy concerns and high data curation costs. Advanced data-driven solutions could lead towards more robust clinical decision support systems and enhanced clinical training. This Perspective critically examines current and emerging advances in synthetic data generation, and highlights its anticipated transformational effect for early and efficient prevention, diagnosis and treatment of gastrointestinal diseases. Research challenges and directions are identified for leveraging the benefits of synthetic data as well as translating and adopting them in clinical workflows. The advent of artificial intelligence modalities signifies new advances in medical practice. This Perspective discusses synthetic data generation in the context of gastrointestinal medicine and provides insights into challenges and limitations.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 10","pages":"776-790"},"PeriodicalIF":57.5,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148272299","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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