Pub Date : 2025-11-17DOI: 10.1038/s41575-025-01138-9
Akwi W. Asombang, Samuel O. Antwi, Abidemi Omonisi, Matthew A. Cooley, Yvonne A. Nartey, Caitlin J. VanLith, Hailemichael Desalegn, Edith Okeke, Fidel Rubagumya, Africa HepatoPancreatoBiliary Cancer Consortium (AHPBCC), Albert T. Yonli, Mohamed El-Kassas, Jackson Chipaila, Bolni Marius Nagalo, Ashraf Omar, Lewis R. Roberts
Hepatopancreatobiliary (HPB) cancers are a major cause of morbidity and mortality worldwide, particularly in Africa, where the risk factors, tumour characteristics, treatment-related factors and survival outcomes are poorly characterized. Despite the high incidence and mortality rates of HPB cancers in Africans, there is a dearth of data on the genetic and non-genetic risk factors for HPB cancers in Africa. The incidence and mortality rates of HPB cancers in Africans can only be substantially reduced by increasing our understanding of the population-specific risk factors and potentially unique underlying tumour biology. Pursuing this goal requires the establishment of robust clinical and population-based registries across the African continent for risk assessment, which will enable the development of strategies for HPB cancer prevention and implementation of surveillance programmes for early cancer detection in individuals at high risk. This goal was the premise for establishing the Africa HepatoPancreatoBiliary Cancer Consortium (AHPBCC). In this Roadmap article, we discuss the AHPBCC’s collaborative efforts to increase knowledge about HPB cancers in Africans and to promote Africa-focused research on HPB cancers. We also provide in-depth discussions on the establishment of cancer registries in Africa, including the challenges, best practices and areas for growth, to improve HPB cancer outcomes in Africa. Despite the high incidence and mortality rates of hepatopancreatobiliary cancers in the African continent, epidemiological and clinical data are scarce. This Roadmap article describes the efforts of the Africa HepatoPancreatoBiliary Cancer Consortium to establish cancer registries in the region.
{"title":"Establishing cancer registries in Africa — focus on hepatopancreatobiliary cancers","authors":"Akwi W. Asombang, Samuel O. Antwi, Abidemi Omonisi, Matthew A. Cooley, Yvonne A. Nartey, Caitlin J. VanLith, Hailemichael Desalegn, Edith Okeke, Fidel Rubagumya, Africa HepatoPancreatoBiliary Cancer Consortium (AHPBCC), Albert T. Yonli, Mohamed El-Kassas, Jackson Chipaila, Bolni Marius Nagalo, Ashraf Omar, Lewis R. Roberts","doi":"10.1038/s41575-025-01138-9","DOIUrl":"10.1038/s41575-025-01138-9","url":null,"abstract":"Hepatopancreatobiliary (HPB) cancers are a major cause of morbidity and mortality worldwide, particularly in Africa, where the risk factors, tumour characteristics, treatment-related factors and survival outcomes are poorly characterized. Despite the high incidence and mortality rates of HPB cancers in Africans, there is a dearth of data on the genetic and non-genetic risk factors for HPB cancers in Africa. The incidence and mortality rates of HPB cancers in Africans can only be substantially reduced by increasing our understanding of the population-specific risk factors and potentially unique underlying tumour biology. Pursuing this goal requires the establishment of robust clinical and population-based registries across the African continent for risk assessment, which will enable the development of strategies for HPB cancer prevention and implementation of surveillance programmes for early cancer detection in individuals at high risk. This goal was the premise for establishing the Africa HepatoPancreatoBiliary Cancer Consortium (AHPBCC). In this Roadmap article, we discuss the AHPBCC’s collaborative efforts to increase knowledge about HPB cancers in Africans and to promote Africa-focused research on HPB cancers. We also provide in-depth discussions on the establishment of cancer registries in Africa, including the challenges, best practices and areas for growth, to improve HPB cancer outcomes in Africa. Despite the high incidence and mortality rates of hepatopancreatobiliary cancers in the African continent, epidemiological and clinical data are scarce. This Roadmap article describes the efforts of the Africa HepatoPancreatoBiliary Cancer Consortium to establish cancer registries in the region.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 2","pages":"189-200"},"PeriodicalIF":51.0,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145541336","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 : 2025-11-14DOI: 10.1038/s41575-025-01154-9
Tommaso L. Parigi, Silvio Danese
A new case report of successful treatment of refractory ulcerative colitis with CD19-directed chimeric antigen receptor T cell therapy sheds light on the role of B lineage cells in disease pathogenesis and the possibility of an ‘immune reset’. This approach could reshape therapeutic strategies, although its long-term efficacy, safety and positioning remain open questions.
{"title":"Rethinking B cells in ulcerative colitis: a CAR T cell opportunity","authors":"Tommaso L. Parigi, Silvio Danese","doi":"10.1038/s41575-025-01154-9","DOIUrl":"10.1038/s41575-025-01154-9","url":null,"abstract":"A new case report of successful treatment of refractory ulcerative colitis with CD19-directed chimeric antigen receptor T cell therapy sheds light on the role of B lineage cells in disease pathogenesis and the possibility of an ‘immune reset’. This approach could reshape therapeutic strategies, although its long-term efficacy, safety and positioning remain open questions.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 1","pages":"4-5"},"PeriodicalIF":51.0,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145515921","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 : 2025-11-12DOI: 10.1038/s41575-025-01150-z
J.-Matthias Löhr, Miroslav Vujasinovic
Patients with pancreatic exocrine insufficiency are treated with pancreatic enzyme replacement therapy. However, there are several challenges facing the future of this treatment, including infectious agents and the presence of microplastics and nanoplastics.
{"title":"The future of treating pancreatic exocrine insufficiency","authors":"J.-Matthias Löhr, Miroslav Vujasinovic","doi":"10.1038/s41575-025-01150-z","DOIUrl":"10.1038/s41575-025-01150-z","url":null,"abstract":"Patients with pancreatic exocrine insufficiency are treated with pancreatic enzyme replacement therapy. However, there are several challenges facing the future of this treatment, including infectious agents and the presence of microplastics and nanoplastics.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 1","pages":"1-2"},"PeriodicalIF":51.0,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145492577","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 : 2025-11-10DOI: 10.1038/s41575-025-01141-0
Julian Schwärzler, Paola Menghini, Charles Dinarello, Fabio Cominelli, Herbert Tilg
Inflammation has a fundamental role in many disorders of the gastrointestinal tract and the liver. Why these organs are particularly prone to acute, but especially chronic, immune-mediated disorders remains unclear; however, the complex exposure to environmental triggers, including the gut microbiota, might be particularly relevant. Cytokines are considered key regulators of inflammatory processes, with IL-1β being one of the first cytokines discovered, more than four decades ago. A whole family of IL-1-related cytokines has been discovered, and their crucial role in many gastrointestinal and liver diseases has been studied in detail. Today, the IL-1 family comprises 22 members, including 11 cytokines and 11 receptors. IL-1 signalling cascades share similarities with Toll-like receptors, initiating acute-phase reactions to environmental and endogenous threats, and are particularly involved in orchestrating innate immune responses, which are the basis of many gastrointestinal and liver disorders. In this article, we discuss the role of the main IL-1 family members in gastrointestinal and liver diseases, focusing on preclinical and clinical research, and we contemplate opportunities for clinical applications. In this Review, the authors discuss the role of the main IL-1 family members in gastrointestinal and liver diseases, focusing on preclinical and clinical research. Opportunities for therapeutic interventions are also outlined.
{"title":"IL-1 family of cytokines in gastrointestinal and liver disorders","authors":"Julian Schwärzler, Paola Menghini, Charles Dinarello, Fabio Cominelli, Herbert Tilg","doi":"10.1038/s41575-025-01141-0","DOIUrl":"10.1038/s41575-025-01141-0","url":null,"abstract":"Inflammation has a fundamental role in many disorders of the gastrointestinal tract and the liver. Why these organs are particularly prone to acute, but especially chronic, immune-mediated disorders remains unclear; however, the complex exposure to environmental triggers, including the gut microbiota, might be particularly relevant. Cytokines are considered key regulators of inflammatory processes, with IL-1β being one of the first cytokines discovered, more than four decades ago. A whole family of IL-1-related cytokines has been discovered, and their crucial role in many gastrointestinal and liver diseases has been studied in detail. Today, the IL-1 family comprises 22 members, including 11 cytokines and 11 receptors. IL-1 signalling cascades share similarities with Toll-like receptors, initiating acute-phase reactions to environmental and endogenous threats, and are particularly involved in orchestrating innate immune responses, which are the basis of many gastrointestinal and liver disorders. In this article, we discuss the role of the main IL-1 family members in gastrointestinal and liver diseases, focusing on preclinical and clinical research, and we contemplate opportunities for clinical applications. In this Review, the authors discuss the role of the main IL-1 family members in gastrointestinal and liver diseases, focusing on preclinical and clinical research. Opportunities for therapeutic interventions are also outlined.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 1","pages":"29-43"},"PeriodicalIF":51.0,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477973","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 : 2025-11-10DOI: 10.1038/s41575-025-01142-z
Matthew Siddle, Rocío Gallego Durán, Deepika Goel, Benjamin J. Renquist, Marie K. Holt, Anna Hadjihambi
The liver is a metabolically flexible tissue, adapting its functions to changes in nutrient availability and physiological states. This adaptability is crucial for maintaining metabolic homeostasis and likely involves communication with the central nervous system through the liver–brain axis. The liver also receives a constant influx of nutrients, hormones and microbial metabolites from the gastrointestinal tract in a multifaceted communication network, the gut–liver–brain axis. Dysregulation of this communication can lead to hepatic encephalopathy and cognitive impairments in early-stage chronic liver disease, such as metabolic dysfunction-associated steatotic liver disease, substantially affecting patient quality of life. This Review examines key signalling pathways along the liver–brain axis: humoral signalling, including metabolites, hepatokines, toxins and inflammation, and neural pathways, focusing on afferent signalling through the common hepatic branch of the vagus nerve. We discuss how each pathway might contribute to behavioural and mood changes in chronic liver disease and the development of hepatic encephalopathy. Although the humoral effects have been studied more extensively, we propose that the afferent vagus nerve is central to liver disease-associated cognitive and behavioural complications. Finally, we highlight how new techniques and tools could advance our understanding of the gut–liver–brain communication that affects behaviour. The liver is a key metabolic organ that influences metabolic homeostasis by communicating with the central nervous system. This Review discusses the role of gut–liver–brain communication in chronic liver disease, highlighting underlying mechanisms and signalling pathways.
{"title":"Mechanistic insights into the liver–brain axis during chronic liver disease","authors":"Matthew Siddle, Rocío Gallego Durán, Deepika Goel, Benjamin J. Renquist, Marie K. Holt, Anna Hadjihambi","doi":"10.1038/s41575-025-01142-z","DOIUrl":"10.1038/s41575-025-01142-z","url":null,"abstract":"The liver is a metabolically flexible tissue, adapting its functions to changes in nutrient availability and physiological states. This adaptability is crucial for maintaining metabolic homeostasis and likely involves communication with the central nervous system through the liver–brain axis. The liver also receives a constant influx of nutrients, hormones and microbial metabolites from the gastrointestinal tract in a multifaceted communication network, the gut–liver–brain axis. Dysregulation of this communication can lead to hepatic encephalopathy and cognitive impairments in early-stage chronic liver disease, such as metabolic dysfunction-associated steatotic liver disease, substantially affecting patient quality of life. This Review examines key signalling pathways along the liver–brain axis: humoral signalling, including metabolites, hepatokines, toxins and inflammation, and neural pathways, focusing on afferent signalling through the common hepatic branch of the vagus nerve. We discuss how each pathway might contribute to behavioural and mood changes in chronic liver disease and the development of hepatic encephalopathy. Although the humoral effects have been studied more extensively, we propose that the afferent vagus nerve is central to liver disease-associated cognitive and behavioural complications. Finally, we highlight how new techniques and tools could advance our understanding of the gut–liver–brain communication that affects behaviour. The liver is a key metabolic organ that influences metabolic homeostasis by communicating with the central nervous system. This Review discusses the role of gut–liver–brain communication in chronic liver disease, highlighting underlying mechanisms and signalling pathways.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 2","pages":"166-188"},"PeriodicalIF":51.0,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477974","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 : 2025-11-05DOI: 10.1038/s41575-025-01134-z
Luis A. Chica Cardenas, Maureen M. Leonard, Megan T. Baldridge, Scott A. Handley
The gut virome is a complex ecosystem characterized by the interplay of diverse viral entities, predominantly bacteriophages and eukaryotic viruses. The gut virome has a critical role in human health by shaping microbial community profiles, modulating host immunity and influencing metabolic processes. Different viral metagenomics approaches have revealed the remarkable diversity of the gut virome, showing individual-specific patterns that evolve over time and adapt dynamically to environmental factors. Perturbations in this community are increasingly associated with chronic immune and inflammatory conditions, metabolic disorders and neurological conditions, highlighting its potential as a diagnostic biomarker and therapeutic target. The early-life gut virome is particularly influential in establishing lifelong health trajectories through its interactions with diet, immune pathways and others, thereby contributing to inflammatory and metabolic regulation. This Review synthesizes current knowledge of gut virome composition, dynamics and functional relevance, critically evaluating evidence distinguishing causal from correlative roles in disease pathogenesis. The interactions of the virome with other microbiome components and host immunity are examined, and emerging translational applications, including phage therapy and biomarker development, are discussed. Integrating these insights while acknowledging methodological challenges provides a comprehensive framework for understanding the complex roles of the gut virome in health and disease. The gut virome is a complex ecosystem and has a critical role in human health. This Review outlines gut virome composition and functional relevance, and its role in human health and disease. Methodological challenges in advancing our knowledge of the gut virome are also discussed.
{"title":"Gut virome dynamics: from commensal to critical player in health and disease","authors":"Luis A. Chica Cardenas, Maureen M. Leonard, Megan T. Baldridge, Scott A. Handley","doi":"10.1038/s41575-025-01134-z","DOIUrl":"10.1038/s41575-025-01134-z","url":null,"abstract":"The gut virome is a complex ecosystem characterized by the interplay of diverse viral entities, predominantly bacteriophages and eukaryotic viruses. The gut virome has a critical role in human health by shaping microbial community profiles, modulating host immunity and influencing metabolic processes. Different viral metagenomics approaches have revealed the remarkable diversity of the gut virome, showing individual-specific patterns that evolve over time and adapt dynamically to environmental factors. Perturbations in this community are increasingly associated with chronic immune and inflammatory conditions, metabolic disorders and neurological conditions, highlighting its potential as a diagnostic biomarker and therapeutic target. The early-life gut virome is particularly influential in establishing lifelong health trajectories through its interactions with diet, immune pathways and others, thereby contributing to inflammatory and metabolic regulation. This Review synthesizes current knowledge of gut virome composition, dynamics and functional relevance, critically evaluating evidence distinguishing causal from correlative roles in disease pathogenesis. The interactions of the virome with other microbiome components and host immunity are examined, and emerging translational applications, including phage therapy and biomarker development, are discussed. Integrating these insights while acknowledging methodological challenges provides a comprehensive framework for understanding the complex roles of the gut virome in health and disease. The gut virome is a complex ecosystem and has a critical role in human health. This Review outlines gut virome composition and functional relevance, and its role in human health and disease. Methodological challenges in advancing our knowledge of the gut virome are also discussed.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 2","pages":"126-144"},"PeriodicalIF":51.0,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145440871","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 : 2025-11-03DOI: 10.1038/s41575-025-01144-x
Xiao-Dong Zhou (, ), Ming-Hua Zheng (, )
The year 2025 has seen substantial advances in the understanding and management of metabolic dysfunction-associated steatotic liver disease, providing new insights into its systemic effects. Emerging evidence in 2025 supports integrated heart–liver co-management, translating the concept into actionable clinical strategies.
{"title":"Heart–liver co-management in MASLD: from concept to clinical practice","authors":"Xiao-Dong Zhou \u0000 (, ), Ming-Hua Zheng \u0000 (, )","doi":"10.1038/s41575-025-01144-x","DOIUrl":"10.1038/s41575-025-01144-x","url":null,"abstract":"The year 2025 has seen substantial advances in the understanding and management of metabolic dysfunction-associated steatotic liver disease, providing new insights into its systemic effects. Emerging evidence in 2025 supports integrated heart–liver co-management, translating the concept into actionable clinical strategies.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 2","pages":"117-118"},"PeriodicalIF":51.0,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145427472","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 : 2025-11-03DOI: 10.1038/s41575-025-01140-1
Tao Zuo (, )
The gut microbiome presents in a multi-kingdom form and tunes host health in various ways. Studies published in 2025 have further pushed this frontier by unveiling the enigmatic roles of the gut fungi and bacteria in cross-organ regulations of host homeostasis through metabolite and immune cell-mediated pathways.
{"title":"Pushing the frontier of gut microbiome health cross-kingdom and cross-organ","authors":"Tao Zuo \u0000 (, )","doi":"10.1038/s41575-025-01140-1","DOIUrl":"10.1038/s41575-025-01140-1","url":null,"abstract":"The gut microbiome presents in a multi-kingdom form and tunes host health in various ways. Studies published in 2025 have further pushed this frontier by unveiling the enigmatic roles of the gut fungi and bacteria in cross-organ regulations of host homeostasis through metabolite and immune cell-mediated pathways.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 2","pages":"112-114"},"PeriodicalIF":51.0,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145427469","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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