Pub Date : 2025-09-18DOI: 10.1038/s41575-025-01117-0
Fiona C. Malcomson, Mihir M. Shah, Urvi A. Shah
Diet modulates not only gastrointestinal cancer risk but also survivorship, providing an opportunity to improve cancer-related outcomes and quality of life through suitable dietary and lifestyle interventions in survivors of cancer. This Comment summarizes the evidence and ongoing trials investigating diet in gastrointestinal cancer survival, including potential underlying mechanisms and future research directions.
{"title":"Food as medicine in gastrointestinal cancer therapy","authors":"Fiona C. Malcomson, Mihir M. Shah, Urvi A. Shah","doi":"10.1038/s41575-025-01117-0","DOIUrl":"10.1038/s41575-025-01117-0","url":null,"abstract":"Diet modulates not only gastrointestinal cancer risk but also survivorship, providing an opportunity to improve cancer-related outcomes and quality of life through suitable dietary and lifestyle interventions in survivors of cancer. This Comment summarizes the evidence and ongoing trials investigating diet in gastrointestinal cancer survival, including potential underlying mechanisms and future research directions.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"22 11","pages":"736-738"},"PeriodicalIF":51.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083623","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 : 2025-09-11DOI: 10.1038/s41575-025-01113-4
Frances J. England, Manqiang Lin, Michael Sigal, Simon J. Leedham
The crypt–villus architecture of the intestinal mucosa is underpinned by dynamic interactions between distinct populations of epithelial, stromal and immune cells. Although the epithelial compartment has attracted substantial attention, there is a growing appreciation for the critical role of mesenchymal cells in shaping epithelial stem cell function and dictating lineage specification. In this Review, we outline how the epithelial and mesenchymal compartments of the developing gut evolve in a mutually dependent manner to establish dynamic reciprocal signalling gradients that maintain adult tissue homeostasis. We discuss how perturbations to this delicate ecosystem result in rapid adaptive cellular responses that act to restore tissue function. Furthermore, we explore how the intricate nature of cell fate interdependence also renders the mucosa susceptible to pathological disruption. Drawing on the latest studies, we highlight the crosstalk networks between the epithelial and stromal compartments that underlie these processes and consider how these insights are informing future research directions and therapeutic strategies. In doing so, we advocate for a shift away from the conventional epithelial-centric paradigm toward a more integrated framework that considers the full spectrum of intercellular interactions maintaining intestinal tissue integrity and shaping disease progression. This Review focuses on epithelial–mesenchymal crosstalk and how these interactions shape development, health and disease in the intestinal mucosa. The dynamic nature of this ecosystem is highlighted, offering insights into cell fate, cellular reprogramming after tissue damage and the pathways co-opted in neoplasia.
{"title":"Defining the mucosal ecosystem: epithelial–mesenchymal interdependence in gastrointestinal health and disease","authors":"Frances J. England, Manqiang Lin, Michael Sigal, Simon J. Leedham","doi":"10.1038/s41575-025-01113-4","DOIUrl":"10.1038/s41575-025-01113-4","url":null,"abstract":"The crypt–villus architecture of the intestinal mucosa is underpinned by dynamic interactions between distinct populations of epithelial, stromal and immune cells. Although the epithelial compartment has attracted substantial attention, there is a growing appreciation for the critical role of mesenchymal cells in shaping epithelial stem cell function and dictating lineage specification. In this Review, we outline how the epithelial and mesenchymal compartments of the developing gut evolve in a mutually dependent manner to establish dynamic reciprocal signalling gradients that maintain adult tissue homeostasis. We discuss how perturbations to this delicate ecosystem result in rapid adaptive cellular responses that act to restore tissue function. Furthermore, we explore how the intricate nature of cell fate interdependence also renders the mucosa susceptible to pathological disruption. Drawing on the latest studies, we highlight the crosstalk networks between the epithelial and stromal compartments that underlie these processes and consider how these insights are informing future research directions and therapeutic strategies. In doing so, we advocate for a shift away from the conventional epithelial-centric paradigm toward a more integrated framework that considers the full spectrum of intercellular interactions maintaining intestinal tissue integrity and shaping disease progression. This Review focuses on epithelial–mesenchymal crosstalk and how these interactions shape development, health and disease in the intestinal mucosa. The dynamic nature of this ecosystem is highlighted, offering insights into cell fate, cellular reprogramming after tissue damage and the pathways co-opted in neoplasia.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"22 11","pages":"741-754"},"PeriodicalIF":51.0,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031828","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 : 2025-09-08DOI: 10.1038/s41575-025-01112-5
Trisha S. Pasricha, Subhash Kulkarni
Enteric dopaminergic signalling has a critical role in gastrointestinal motility, maintaining mucosal integrity and modulating the gut microbiome. In this Review, we provide an overview of dopamine metabolism and signalling pathways in the central nervous system and periphery and their effects on gastrointestinal health and disease. We describe the physiological role of enteric dopamine, including a discussion of therapeutic opportunities and future research needs. With rising interest in the gut-first hypothesis of Parkinson disease, an area of great interest is how dopaminergic depletion in the gut could indicate future neurological dysfunction. In addition, dopamine signalling has been found to influence microbiome colonization resistance against enteric pathogens and immunoregulation. Emerging data on the effect of dopamine replacement therapy on gastrointestinal symptoms, across a range of conditions from neurodegenerative disease to inflammatory bowel disease, are also explored. In this Review, Pasricha and Kulkarni describe the role of dopaminergic signalling pathways in the central nervous system and periphery, and their role in gastrointestinal health and disease. In addition, they discuss emerging evidence and future directions.
{"title":"Dopaminergic signalling in gastrointestinal health and disease","authors":"Trisha S. Pasricha, Subhash Kulkarni","doi":"10.1038/s41575-025-01112-5","DOIUrl":"10.1038/s41575-025-01112-5","url":null,"abstract":"Enteric dopaminergic signalling has a critical role in gastrointestinal motility, maintaining mucosal integrity and modulating the gut microbiome. In this Review, we provide an overview of dopamine metabolism and signalling pathways in the central nervous system and periphery and their effects on gastrointestinal health and disease. We describe the physiological role of enteric dopamine, including a discussion of therapeutic opportunities and future research needs. With rising interest in the gut-first hypothesis of Parkinson disease, an area of great interest is how dopaminergic depletion in the gut could indicate future neurological dysfunction. In addition, dopamine signalling has been found to influence microbiome colonization resistance against enteric pathogens and immunoregulation. Emerging data on the effect of dopamine replacement therapy on gastrointestinal symptoms, across a range of conditions from neurodegenerative disease to inflammatory bowel disease, are also explored. In this Review, Pasricha and Kulkarni describe the role of dopaminergic signalling pathways in the central nervous system and periphery, and their role in gastrointestinal health and disease. In addition, they discuss emerging evidence and future directions.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"22 10","pages":"696-707"},"PeriodicalIF":51.0,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017617","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 : 2025-09-03DOI: 10.1038/s41575-025-01106-3
Chaoran Yang, Matthew Snelson, Assam El-Osta, Francine Z. Marques
The effects of diet and nutrition extend beyond individual health: food intake before conception or during pregnancy and lactation can affect the health of offspring. Diet is one of the most powerful modulators of the gut microbiome, influencing gene–environment interactions, with several emerging mechanisms pointing to the microbiome–metabolite–epigenome axis. In this Review, we discuss the effect of dietary changes on the gametes (‘gut–germline axis’) or in utero (‘gut–neonatal axis’) that may change the predisposition of offspring to several non-communicable diseases. Examples of diets discussed are those that detrimentally modulate the parental microbiota and lead to epigenetic changes in the progeny, including Western diets characterized by high saturated fat and low protein or fibre intake. We summarize studies using animal models, which suggest that these diets can have long-lasting effects on the offspring microbiome, epigenome and phenotype, particularly across the cardiometabolic and immune systems, and discuss the limitations of current studies as well as future directions for the field. Translational research investigating the benefits of parental dietary interventions before and during pregnancy, mainly using personalized approaches, is needed. This would, in turn, reduce rates of non-communicable diseases in generations to come. In this Review, Marques and colleagues discuss the evidence regarding the effects of parental diet on the health of offspring, with a focus on how changes to the gut microbiome alter epigenomic responses in the offspring.
{"title":"Parental diet and offspring health: a role for the gut microbiome via epigenetics","authors":"Chaoran Yang, Matthew Snelson, Assam El-Osta, Francine Z. Marques","doi":"10.1038/s41575-025-01106-3","DOIUrl":"10.1038/s41575-025-01106-3","url":null,"abstract":"The effects of diet and nutrition extend beyond individual health: food intake before conception or during pregnancy and lactation can affect the health of offspring. Diet is one of the most powerful modulators of the gut microbiome, influencing gene–environment interactions, with several emerging mechanisms pointing to the microbiome–metabolite–epigenome axis. In this Review, we discuss the effect of dietary changes on the gametes (‘gut–germline axis’) or in utero (‘gut–neonatal axis’) that may change the predisposition of offspring to several non-communicable diseases. Examples of diets discussed are those that detrimentally modulate the parental microbiota and lead to epigenetic changes in the progeny, including Western diets characterized by high saturated fat and low protein or fibre intake. We summarize studies using animal models, which suggest that these diets can have long-lasting effects on the offspring microbiome, epigenome and phenotype, particularly across the cardiometabolic and immune systems, and discuss the limitations of current studies as well as future directions for the field. Translational research investigating the benefits of parental dietary interventions before and during pregnancy, mainly using personalized approaches, is needed. This would, in turn, reduce rates of non-communicable diseases in generations to come. In this Review, Marques and colleagues discuss the evidence regarding the effects of parental diet on the health of offspring, with a focus on how changes to the gut microbiome alter epigenomic responses in the offspring.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"22 11","pages":"755-772"},"PeriodicalIF":51.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960109","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 : 2025-09-03DOI: 10.1038/s41575-025-01111-6
Florian Huwyler, Jonas Binz, Leslie Cunningham, Matthias Pfister, Martin J. Schuler, Mark W. Tibbitt, Pierre-Alain Clavien
Machine perfusion is an emerging and transformative technology for dynamic organ preservation, assessment and repair. Whereas allografts continuously degrade during static cold storage, short-term perfusion can preserve high-quality organs for hours, enabling assessment, regional transport and improved logistics. Long-term perfusion for multiple days might extend the potential of clinical machine perfusion in the future, allowing for the assessment, reconditioning and repair of marginal or injured grafts for which more time is needed. In addition, it might convert transplantation, which is now semi-elective thanks to short-term perfusion, to a fully elective procedure via customized machines and associated protocols that maintain organs ex situ for up to 2 weeks. The advent of long-term organ perfusion provides tremendous potential to improve organ evaluation and selection, to recondition or repair marginal grafts and, ultimately, to expand the pool of grafts available for transplantation. In this Perspective, we discuss design considerations, guidelines for use, and future perspectives of machine perfusion in the context of organ assessment and repair, with a focus on the liver. In this Perspective article, Huwyler, Binz and colleagues discuss the future of long-term normothermic machine perfusion for livers and propose a staged assessment approach for ex situ perfused organs.
{"title":"Beyond preservation: future machine perfusion for liver assessment and repair","authors":"Florian Huwyler, Jonas Binz, Leslie Cunningham, Matthias Pfister, Martin J. Schuler, Mark W. Tibbitt, Pierre-Alain Clavien","doi":"10.1038/s41575-025-01111-6","DOIUrl":"10.1038/s41575-025-01111-6","url":null,"abstract":"Machine perfusion is an emerging and transformative technology for dynamic organ preservation, assessment and repair. Whereas allografts continuously degrade during static cold storage, short-term perfusion can preserve high-quality organs for hours, enabling assessment, regional transport and improved logistics. Long-term perfusion for multiple days might extend the potential of clinical machine perfusion in the future, allowing for the assessment, reconditioning and repair of marginal or injured grafts for which more time is needed. In addition, it might convert transplantation, which is now semi-elective thanks to short-term perfusion, to a fully elective procedure via customized machines and associated protocols that maintain organs ex situ for up to 2 weeks. The advent of long-term organ perfusion provides tremendous potential to improve organ evaluation and selection, to recondition or repair marginal grafts and, ultimately, to expand the pool of grafts available for transplantation. In this Perspective, we discuss design considerations, guidelines for use, and future perspectives of machine perfusion in the context of organ assessment and repair, with a focus on the liver. In this Perspective article, Huwyler, Binz and colleagues discuss the future of long-term normothermic machine perfusion for livers and propose a staged assessment approach for ex situ perfused organs.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"22 10","pages":"721-733"},"PeriodicalIF":51.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930667","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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