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}
Pub Date : 2025-10-28DOI: 10.1038/s41575-025-01132-1
Nick J. Spencer, Timothy J. Hibberd, Hongzhen Hu
Understanding the locations of extrinsic sensory nerve endings in the gastrointestinal tract and their mechanisms of activation is essential to advancing our understanding of how communication along the gut–brain axis affects health and disease. The gastrointestinal tract detects diverse stimuli (chemical, mechanical and thermal signals) via two major types of primary afferent (sensory) nerves: vagal and spinal afferents. Viscerofugal neurons represent a third pathway that has been indirectly implicated in gut–brain signalling. These spinal and vagal afferents transmit sensory signals to the brain through distinct pathways, and although the origins of their nerve cell bodies are known, their nerve endings remain poorly understood. New evidence indicates that single dorsal root ganglia neurons can give rise to multiple different morphological types of endings within different gut layers, and that Piezo2 channels have a major role in detecting mechanosensory stimuli by gut-projecting spinal afferents. Morphological studies suggest that substances released from enteroendocrine cells can activate the terminals of vagal and spinal afferent endings within the mucosa through a paracrine mechanism. Here, we review the distinct spinal and vagal afferent types alongside viscerofugal pathways revealed by advances in neurogenetic techniques and high-resolution anterograde tracing, linking them to their physiological role in gut–brain communication. This Review explores the different types of sensory nerves involved in gut–brain communication, detailing the locations of these nerve endings in the gut and their mechanisms of activation. Insights and new information regarding spinal and vagal afferents alongside viscerofugal neurons are detailed.
{"title":"Gut–brain communication: types of sensory nerves and mechanisms of activation","authors":"Nick J. Spencer, Timothy J. Hibberd, Hongzhen Hu","doi":"10.1038/s41575-025-01132-1","DOIUrl":"10.1038/s41575-025-01132-1","url":null,"abstract":"Understanding the locations of extrinsic sensory nerve endings in the gastrointestinal tract and their mechanisms of activation is essential to advancing our understanding of how communication along the gut–brain axis affects health and disease. The gastrointestinal tract detects diverse stimuli (chemical, mechanical and thermal signals) via two major types of primary afferent (sensory) nerves: vagal and spinal afferents. Viscerofugal neurons represent a third pathway that has been indirectly implicated in gut–brain signalling. These spinal and vagal afferents transmit sensory signals to the brain through distinct pathways, and although the origins of their nerve cell bodies are known, their nerve endings remain poorly understood. New evidence indicates that single dorsal root ganglia neurons can give rise to multiple different morphological types of endings within different gut layers, and that Piezo2 channels have a major role in detecting mechanosensory stimuli by gut-projecting spinal afferents. Morphological studies suggest that substances released from enteroendocrine cells can activate the terminals of vagal and spinal afferent endings within the mucosa through a paracrine mechanism. Here, we review the distinct spinal and vagal afferent types alongside viscerofugal pathways revealed by advances in neurogenetic techniques and high-resolution anterograde tracing, linking them to their physiological role in gut–brain communication. This Review explores the different types of sensory nerves involved in gut–brain communication, detailing the locations of these nerve endings in the gut and their mechanisms of activation. Insights and new information regarding spinal and vagal afferents alongside viscerofugal neurons are detailed.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 2","pages":"145-165"},"PeriodicalIF":51.0,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145381210","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 : 2025-10-27DOI: 10.1038/s41575-025-01133-0
A new Series on ‘Nutrition’ is launched exploring how dietary components influence physiological processes and the complex links between dietary patterns and health determinants.
一个关于“营养”的新系列开始探索饮食成分如何影响生理过程以及饮食模式与健康决定因素之间的复杂联系。
{"title":"Advancing nutrition science for global health","authors":"","doi":"10.1038/s41575-025-01133-0","DOIUrl":"10.1038/s41575-025-01133-0","url":null,"abstract":"A new Series on ‘Nutrition’ is launched exploring how dietary components influence physiological processes and the complex links between dietary patterns and health determinants.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"22 11","pages":"735-735"},"PeriodicalIF":51.0,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41575-025-01133-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145371939","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}
Pub Date : 2025-10-23DOI: 10.1038/s41575-025-01145-w
Sarah A. Taylor, Gary D. Bader, Sonya MacParland, Alan C. Mullen, Tallulah Andrews, Alex G. Cuenca, Ramanuj DasGupta, Adam J. Gehring, Dominic Grün, Martin Guilliams, Aliya Gulamhusein, Neil C. Henderson, Gideon Hirschfield, Stacey S. Huppert, Shalev Itzkovitz, Z. Gordon Jiang, Georg M. Lauer, Ian McGilvray, Krupa R. Mysore, Carlos J. Pirola, Gerald Quon, Mohammad Rahbari, Aviv Regev, Amanda Ricciuto, Charlotte L. Scott, Ankur Sharma, Silvia Sookoian, Michele M. Tana, Sarah A. Teichmann, Ludovic Vallier, Ioannis S. Vlachos, Bruce Wang, Mei Zhen
{"title":"Author Correction: Towards a reference cell atlas of liver diversity over the human lifespan","authors":"Sarah A. Taylor, Gary D. Bader, Sonya MacParland, Alan C. Mullen, Tallulah Andrews, Alex G. Cuenca, Ramanuj DasGupta, Adam J. Gehring, Dominic Grün, Martin Guilliams, Aliya Gulamhusein, Neil C. Henderson, Gideon Hirschfield, Stacey S. Huppert, Shalev Itzkovitz, Z. Gordon Jiang, Georg M. Lauer, Ian McGilvray, Krupa R. Mysore, Carlos J. Pirola, Gerald Quon, Mohammad Rahbari, Aviv Regev, Amanda Ricciuto, Charlotte L. Scott, Ankur Sharma, Silvia Sookoian, Michele M. Tana, Sarah A. Teichmann, Ludovic Vallier, Ioannis S. Vlachos, Bruce Wang, Mei Zhen","doi":"10.1038/s41575-025-01145-w","DOIUrl":"10.1038/s41575-025-01145-w","url":null,"abstract":"","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 1","pages":"110-110"},"PeriodicalIF":51.0,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41575-025-01145-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145351512","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}
Pub Date : 2025-10-20DOI: 10.1038/s41575-025-01129-w
Celine Deraison, Nathalie Vergnolle
Extracellular proteases, originating from the host or the microbiota, are key signalling molecules involved in cellular communication with the environment. They signal through a wide array of mechanisms, ranging from receptor activation to protein transformation and even degradation. Protease signals are irreversible, as it involves the cleavage of proteins. Therefore, proteases are tightly controlled, and must be understood within the context of the complex networks in which they operate — their activity is tightly regulated by access to specific substrates and the presence of inhibitors. The intestine is particularly exposed to extracellular proteases, which have major roles in gut physiology: digestion, food antigen processing, barrier function, epithelial renewal and microbiome homeostasis. Dysregulated proteolytic balance is associated with intestinal pathologies including inflammatory bowel disease, irritable bowel syndrome, coeliac disease and colorectal cancer. Extracellular proteases are major contributors to a number of gut dysfunctions, including microbiota dysbiosis, barrier dysfunction, matrix remodelling, activation of mucosal immunity and nociceptive or motility abnormalities. Consequently, proteolytic homeostasis at the intestinal mucosa surface has become a goal for intestinal health, and new therapeutic options targeting the interplay among proteases, their inhibitors and their substrates have been explored. In this Review, Deraison and Vergnolle describe the role of extracellular proteases and protease inhibitors in gastrointestinal physiology and in diseases including inflammatory bowel disease, irritable bowel syndrome and colorectal cancer. They also explore emerging therapeutic options for restoring proteolytic balance.
{"title":"Proteases in intestinal health and disease","authors":"Celine Deraison, Nathalie Vergnolle","doi":"10.1038/s41575-025-01129-w","DOIUrl":"10.1038/s41575-025-01129-w","url":null,"abstract":"Extracellular proteases, originating from the host or the microbiota, are key signalling molecules involved in cellular communication with the environment. They signal through a wide array of mechanisms, ranging from receptor activation to protein transformation and even degradation. Protease signals are irreversible, as it involves the cleavage of proteins. Therefore, proteases are tightly controlled, and must be understood within the context of the complex networks in which they operate — their activity is tightly regulated by access to specific substrates and the presence of inhibitors. The intestine is particularly exposed to extracellular proteases, which have major roles in gut physiology: digestion, food antigen processing, barrier function, epithelial renewal and microbiome homeostasis. Dysregulated proteolytic balance is associated with intestinal pathologies including inflammatory bowel disease, irritable bowel syndrome, coeliac disease and colorectal cancer. Extracellular proteases are major contributors to a number of gut dysfunctions, including microbiota dysbiosis, barrier dysfunction, matrix remodelling, activation of mucosal immunity and nociceptive or motility abnormalities. Consequently, proteolytic homeostasis at the intestinal mucosa surface has become a goal for intestinal health, and new therapeutic options targeting the interplay among proteases, their inhibitors and their substrates have been explored. In this Review, Deraison and Vergnolle describe the role of extracellular proteases and protease inhibitors in gastrointestinal physiology and in diseases including inflammatory bowel disease, irritable bowel syndrome and colorectal cancer. They also explore emerging therapeutic options for restoring proteolytic balance.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 1","pages":"6-28"},"PeriodicalIF":51.0,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145331919","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 : 2025-10-13DOI: 10.1038/s41575-025-01114-3
Sarah A. Taylor, Gary D. Bader, Sonya MacParland, Alan C. Mullen, Tallulah Andrews, Alex G. Cuenca, Ramanuj DasGupta, Adam J. Gehring, Dominic Grün, Martin Guilliams, Aliya Gulamhusein, Neil C. Henderson, Gideon Hirschfield, Stacey S. Huppert, Shalev Itzkovitz, Z. Gordon Jiang, Georg M. Lauer, Ian McGilvray, Krupa R. Mysore, Carlos J. Pirola, Gerald Quon, Mohammad Rahbari, Aviv Regev, Amanda Ricciuto, Charlotte L. Scott, Ankur Sharma, Silvia Sookoian, Michele M. Tana, Sarah A. Teichmann, Ludovic Vallier, Ioannis S. Vlachos, Bruce Wang, Mei Zhen
The goal of the Human Liver Cell Atlas (HLiCA) is to create a comprehensive map that defines the normal functions of diverse liver cell types and their spatial relationships over the human lifespan. This project fits within the goals of the Human Cell Atlas to create comprehensive reference maps of all human cells as a basis for both understanding human health and diagnosing, monitoring and treating disease. Through collection of samples from diverse individuals, data integration across technologies and overcoming liver-specific challenges for experimental methods, the HLiCA will map as many cell types and states as possible in healthy human livers from individuals across all ages and many ancestries. Establishing this HLiCA of healthy livers is a critical step to begin to understand perturbations in disease. The HLiCA will be available on an open-access platform to facilitate data sharing and dissemination. We expect that creation of the HLiCA will help to lay the foundation for new research initiatives to advance our understanding of liver disease, improve methods of tissue engineering, and identify novel prognostic biomarkers and therapies to improve patient outcomes. We describe key experimental and computational challenges to overcome in building the atlas and the potential impact of the atlas on disease research. This Roadmap presents and outlines the creation of the Human Liver Cell Atlas as a reference map and resource for the liver community, providing an overview of the steps needed to build the atlas, as well as outlining the major challenges and potential of this venture.
{"title":"Towards a reference cell atlas of liver diversity over the human lifespan","authors":"Sarah A. Taylor, Gary D. Bader, Sonya MacParland, Alan C. Mullen, Tallulah Andrews, Alex G. Cuenca, Ramanuj DasGupta, Adam J. Gehring, Dominic Grün, Martin Guilliams, Aliya Gulamhusein, Neil C. Henderson, Gideon Hirschfield, Stacey S. Huppert, Shalev Itzkovitz, Z. Gordon Jiang, Georg M. Lauer, Ian McGilvray, Krupa R. Mysore, Carlos J. Pirola, Gerald Quon, Mohammad Rahbari, Aviv Regev, Amanda Ricciuto, Charlotte L. Scott, Ankur Sharma, Silvia Sookoian, Michele M. Tana, Sarah A. Teichmann, Ludovic Vallier, Ioannis S. Vlachos, Bruce Wang, Mei Zhen","doi":"10.1038/s41575-025-01114-3","DOIUrl":"10.1038/s41575-025-01114-3","url":null,"abstract":"The goal of the Human Liver Cell Atlas (HLiCA) is to create a comprehensive map that defines the normal functions of diverse liver cell types and their spatial relationships over the human lifespan. This project fits within the goals of the Human Cell Atlas to create comprehensive reference maps of all human cells as a basis for both understanding human health and diagnosing, monitoring and treating disease. Through collection of samples from diverse individuals, data integration across technologies and overcoming liver-specific challenges for experimental methods, the HLiCA will map as many cell types and states as possible in healthy human livers from individuals across all ages and many ancestries. Establishing this HLiCA of healthy livers is a critical step to begin to understand perturbations in disease. The HLiCA will be available on an open-access platform to facilitate data sharing and dissemination. We expect that creation of the HLiCA will help to lay the foundation for new research initiatives to advance our understanding of liver disease, improve methods of tissue engineering, and identify novel prognostic biomarkers and therapies to improve patient outcomes. We describe key experimental and computational challenges to overcome in building the atlas and the potential impact of the atlas on disease research. This Roadmap presents and outlines the creation of the Human Liver Cell Atlas as a reference map and resource for the liver community, providing an overview of the steps needed to build the atlas, as well as outlining the major challenges and potential of this venture.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 1","pages":"97-109"},"PeriodicalIF":51.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283451","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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