Pub Date : 2026-01-22DOI: 10.1038/s41575-025-01171-8
Eirini Dimidi,Kevin Whelan,S Mark Scott
{"title":"Dietary guidelines for gastrointestinal disorders: key to optimizing practice but more work needed.","authors":"Eirini Dimidi,Kevin Whelan,S Mark Scott","doi":"10.1038/s41575-025-01171-8","DOIUrl":"https://doi.org/10.1038/s41575-025-01171-8","url":null,"abstract":"","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"103 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021685","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 : 2026-01-22DOI: 10.1038/s41575-026-01173-0
Rachel H Davis,Robert V Bryant,Peter R Gibson,Alice S Day
Protein is an essential nutrient in the human diet. Global Westernization and modern dietary trends have seen protein become a more substantial contributor to the Western diet, with dietary sources expanding beyond traditional wholefoods to a myriad of processed protein-enriched food products. Although dietary protein is critical for human health, it has also been implicated in colonic health and disease both directly via the microbial fermentation of protein entering the colonic environment and indirectly by affecting the intake of other nutrients in the diet such as fibre. Although protein digestion in the small intestine is highly efficient, there are numerous factors that can influence the capacity for protein digestion and absorption, particularly dietary factors representative of modern-day protein intakes such as high protein diets and food manufacturing. The subsequent fermentation of protein and production of microbial metabolites in the colon is in turn affected by the source of protein entering the colon and the presence of fibre. In this Review, we examine factors that influence human digestion and absorption of protein in the small intestine and protein fermentation in the colon, describing implications for colonic health and disease.
{"title":"The fate of dietary protein in the gastrointestinal tract and implications for colonic disease.","authors":"Rachel H Davis,Robert V Bryant,Peter R Gibson,Alice S Day","doi":"10.1038/s41575-026-01173-0","DOIUrl":"https://doi.org/10.1038/s41575-026-01173-0","url":null,"abstract":"Protein is an essential nutrient in the human diet. Global Westernization and modern dietary trends have seen protein become a more substantial contributor to the Western diet, with dietary sources expanding beyond traditional wholefoods to a myriad of processed protein-enriched food products. Although dietary protein is critical for human health, it has also been implicated in colonic health and disease both directly via the microbial fermentation of protein entering the colonic environment and indirectly by affecting the intake of other nutrients in the diet such as fibre. Although protein digestion in the small intestine is highly efficient, there are numerous factors that can influence the capacity for protein digestion and absorption, particularly dietary factors representative of modern-day protein intakes such as high protein diets and food manufacturing. The subsequent fermentation of protein and production of microbial metabolites in the colon is in turn affected by the source of protein entering the colon and the presence of fibre. In this Review, we examine factors that influence human digestion and absorption of protein in the small intestine and protein fermentation in the colon, describing implications for colonic health and disease.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"29 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021684","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 : 2026-01-09DOI: 10.1038/s41575-025-01170-9
Eileen M. O’Reilly
Some of the highlights in the pancreatic cancer field in 2025 include long-term data on personalized neoantigen vaccine approaches in resected pancreatic adenocarcinoma, detailed clinico-genomic analyses of large clinical trial datasets, and therapeutic strategies for early-stage disease.
{"title":"Pancreatic cancer: advances in immunology, translational analyses and therapeutic paradigms","authors":"Eileen M. O’Reilly","doi":"10.1038/s41575-025-01170-9","DOIUrl":"10.1038/s41575-025-01170-9","url":null,"abstract":"Some of the highlights in the pancreatic cancer field in 2025 include long-term data on personalized neoantigen vaccine approaches in resected pancreatic adenocarcinoma, detailed clinico-genomic analyses of large clinical trial datasets, and therapeutic strategies for early-stage disease.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 2","pages":"115-116"},"PeriodicalIF":51.0,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145937616","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 : 2026-01-09DOI: 10.1038/s41575-026-01172-1
Eleni Kotsiliti
{"title":"Drug approvals in 2025 in gastroenterology and hepatology","authors":"Eleni Kotsiliti","doi":"10.1038/s41575-026-01172-1","DOIUrl":"10.1038/s41575-026-01172-1","url":null,"abstract":"","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"23 2","pages":"111-111"},"PeriodicalIF":51.0,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145937617","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 : 2026-01-09DOI: 10.1038/s41575-025-01168-3
Yoshio Yamauchi,Laura J Sharpe,Andrew J Brown
Increasingly, cholesterol is implicated in diseases beyond the cardiovascular system. Major diseases of the gastrointestinal tract and liver are a case in point and are a focus of this Review. Particularly active in whole-body cholesterol metabolism, the gut and liver are the major organs that produce and secrete plasma lipoproteins, specifically chylomicrons, very-low-density lipoprotein and high-density lipoprotein. In addition, the liver is the only organ in which cholesterol is converted into bile acids. In this Review, we summarize how the liver and gut handle cholesterol to achieve homeostasis. A multitude of diverse and elaborate mechanisms strictly regulate whole-body cholesterol homeostasis by maintaining crucial liver and gut functions, notably cholesterol biosynthesis, absorption, metabolism, transport and excretion. Perturbation of cholesterol homeostasis is associated with liver and gut diseases, including metabolic dysfunction-associated steatotic liver disease, hepatocellular carcinoma and colorectal cancer. Therefore, the molecular machinery involved in cholesterol regulation is of great therapeutic interest. We provide an overview of how cholesterol balance is normally maintained, how its dysregulation can contribute to liver and gut diseases, and how cholesterol homeostasis is targetable to combat these diseases.
{"title":"Balancing cholesterol metabolism in the liver and gut: perspectives in health and disease.","authors":"Yoshio Yamauchi,Laura J Sharpe,Andrew J Brown","doi":"10.1038/s41575-025-01168-3","DOIUrl":"https://doi.org/10.1038/s41575-025-01168-3","url":null,"abstract":"Increasingly, cholesterol is implicated in diseases beyond the cardiovascular system. Major diseases of the gastrointestinal tract and liver are a case in point and are a focus of this Review. Particularly active in whole-body cholesterol metabolism, the gut and liver are the major organs that produce and secrete plasma lipoproteins, specifically chylomicrons, very-low-density lipoprotein and high-density lipoprotein. In addition, the liver is the only organ in which cholesterol is converted into bile acids. In this Review, we summarize how the liver and gut handle cholesterol to achieve homeostasis. A multitude of diverse and elaborate mechanisms strictly regulate whole-body cholesterol homeostasis by maintaining crucial liver and gut functions, notably cholesterol biosynthesis, absorption, metabolism, transport and excretion. Perturbation of cholesterol homeostasis is associated with liver and gut diseases, including metabolic dysfunction-associated steatotic liver disease, hepatocellular carcinoma and colorectal cancer. Therefore, the molecular machinery involved in cholesterol regulation is of great therapeutic interest. We provide an overview of how cholesterol balance is normally maintained, how its dysregulation can contribute to liver and gut diseases, and how cholesterol homeostasis is targetable to combat these diseases.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"57 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145937615","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 : 2026-01-08DOI: 10.1038/s41575-025-01167-4
Mohamed El-Kassas, Zobair M Younossi
{"title":"Preventive hepatology for MASLD in the MENA region: reframing care from late-stage treatment to early intervention.","authors":"Mohamed El-Kassas, Zobair M Younossi","doi":"10.1038/s41575-025-01167-4","DOIUrl":"https://doi.org/10.1038/s41575-025-01167-4","url":null,"abstract":"","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":" ","pages":""},"PeriodicalIF":51.0,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145934304","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 : 2026-01-05DOI: 10.1038/s41575-025-01159-4
S K Sarin,Ashok Choudhury,Anupam Kumar,Nadim Mahmud,G H Lee,Qin Ning,Soek-Siam Tan,Kessarin Thanapirom,Vinod Arora,Nobuaki Nakayama,Jun Li,Constantine J Karvellas
Acute-on-chronic liver failure (ACLF) is a complex syndrome characterized by acute hepatic decompensation superimposed on pre-existing chronic liver disease or cirrhosis that is associated with acute worsening of portal hypertension, increased risk of infection, organ dysfunction and high short-term mortality. This Review provides a comprehensive update on definitions, pathophysiological mechanisms, clinical presentation and management of ACLF. The severe hepatic injury in ACLF triggers systemic inflammation, which is driven by damage-associated molecular patterns, gut-derived microbial products, and immunometabolic and functional dysregulation. Immune dysfunction can range from hyperinflammation and hypercytokinaemia to immune paresis, which in turn predisposes patients to infection and organ failure. The principles of ACLF management prioritize ameliorating the acute hepatic insult, managing portal hypertension, preventing organ failure and optimizing patients who are eligible for liver transplantation. Emerging options include novel therapies targeting immune modulation and liver regeneration, therapeutic plasma exchange and artificial liver support systems. Well-defined criteria for prompt interventions and selection of patients for transplantation within the first week after diagnosis - the 'golden window' - have improved outcomes of liver transplantation in patients with ACLF. The Kyoto ACLF Consensus reflects global efforts on unifying definitions, simplifying treatment end points, refining prediction tools, and filling the void of targeted non-transplantation interventions to improve outcomes in patients with ACLF; however, large knowledge gaps remain and further research is needed.
{"title":"Acute-on-chronic liver failure: pathophysiological mechanisms and clinical management.","authors":"S K Sarin,Ashok Choudhury,Anupam Kumar,Nadim Mahmud,G H Lee,Qin Ning,Soek-Siam Tan,Kessarin Thanapirom,Vinod Arora,Nobuaki Nakayama,Jun Li,Constantine J Karvellas","doi":"10.1038/s41575-025-01159-4","DOIUrl":"https://doi.org/10.1038/s41575-025-01159-4","url":null,"abstract":"Acute-on-chronic liver failure (ACLF) is a complex syndrome characterized by acute hepatic decompensation superimposed on pre-existing chronic liver disease or cirrhosis that is associated with acute worsening of portal hypertension, increased risk of infection, organ dysfunction and high short-term mortality. This Review provides a comprehensive update on definitions, pathophysiological mechanisms, clinical presentation and management of ACLF. The severe hepatic injury in ACLF triggers systemic inflammation, which is driven by damage-associated molecular patterns, gut-derived microbial products, and immunometabolic and functional dysregulation. Immune dysfunction can range from hyperinflammation and hypercytokinaemia to immune paresis, which in turn predisposes patients to infection and organ failure. The principles of ACLF management prioritize ameliorating the acute hepatic insult, managing portal hypertension, preventing organ failure and optimizing patients who are eligible for liver transplantation. Emerging options include novel therapies targeting immune modulation and liver regeneration, therapeutic plasma exchange and artificial liver support systems. Well-defined criteria for prompt interventions and selection of patients for transplantation within the first week after diagnosis - the 'golden window' - have improved outcomes of liver transplantation in patients with ACLF. The Kyoto ACLF Consensus reflects global efforts on unifying definitions, simplifying treatment end points, refining prediction tools, and filling the void of targeted non-transplantation interventions to improve outcomes in patients with ACLF; however, large knowledge gaps remain and further research is needed.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"18 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145897512","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 : 2026-01-02DOI: 10.1038/s41575-025-01164-7
Salomé S Pinho, Joana Torres, Jean-Frederic Colombel
Glycans are essential components of homeostatic networks, acting as fine tuners of immunological responses, and are therefore promising targets for manipulating immune tolerance. Glycans shield the entire gut mucosa surface, contributing to epithelial barrier integrity. Moreover, most microorganisms expose glycoconjugates on their surfaces, making glycans essential molecules in the crosstalk between host immune response and the gut microbiota. The vast amount of biological information encoded by mucosal glycans is deciphered by a variety of glycan-binding proteins that translate glycan recognition into either pro-inflammatory or anti-inflammatory responses. Current evidence from inflammatory bowel disease (IBD) has highlighted the prominent role of glycans in establishing and regulating key cellular and molecular pathways underlying the transition from health to intestinal inflammation, with implications for understanding IBD immunopathogenesis and for IBD prediction and prevention. In this Review, we discuss current advances, emerging challenges and future prospects in exploiting the power of the mucosal glycocalyx and the glycome as master coordinators of the immunoregulatory networks in IBD from the preclinical phase to established diagnosis. We discuss the clinical utility of the glycome as a serological biomarker with diagnostic, prognostic and predictive value, and as a potential new target for preventive intervention strategies in IBD.
{"title":"Mucosal glycans: key drivers of the development of inflammatory bowel disease and a potential new therapeutic target.","authors":"Salomé S Pinho, Joana Torres, Jean-Frederic Colombel","doi":"10.1038/s41575-025-01164-7","DOIUrl":"https://doi.org/10.1038/s41575-025-01164-7","url":null,"abstract":"<p><p>Glycans are essential components of homeostatic networks, acting as fine tuners of immunological responses, and are therefore promising targets for manipulating immune tolerance. Glycans shield the entire gut mucosa surface, contributing to epithelial barrier integrity. Moreover, most microorganisms expose glycoconjugates on their surfaces, making glycans essential molecules in the crosstalk between host immune response and the gut microbiota. The vast amount of biological information encoded by mucosal glycans is deciphered by a variety of glycan-binding proteins that translate glycan recognition into either pro-inflammatory or anti-inflammatory responses. Current evidence from inflammatory bowel disease (IBD) has highlighted the prominent role of glycans in establishing and regulating key cellular and molecular pathways underlying the transition from health to intestinal inflammation, with implications for understanding IBD immunopathogenesis and for IBD prediction and prevention. In this Review, we discuss current advances, emerging challenges and future prospects in exploiting the power of the mucosal glycocalyx and the glycome as master coordinators of the immunoregulatory networks in IBD from the preclinical phase to established diagnosis. We discuss the clinical utility of the glycome as a serological biomarker with diagnostic, prognostic and predictive value, and as a potential new target for preventive intervention strategies in IBD.</p>","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":" ","pages":""},"PeriodicalIF":51.0,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889634","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 : 2025-12-22DOI: 10.1038/s41575-025-01166-5
Pierfrancesco Visaggi,Edoardo V Savarino
{"title":"Potassium-competitive acid blockers for the management of gastroesophageal reflux disease.","authors":"Pierfrancesco Visaggi,Edoardo V Savarino","doi":"10.1038/s41575-025-01166-5","DOIUrl":"https://doi.org/10.1038/s41575-025-01166-5","url":null,"abstract":"","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"29 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145807886","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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