Pub Date : 2025-07-28DOI: 10.1038/s41575-025-01099-z
David G. Le Couteur, Meng C. Ngu, Nicholas J. Hunt, Amanda E. Brandon, Stephen J. Simpson, Victoria C. Cogger
As the global population ages, research on the biology of ageing and its role in chronic disease is expanding, alongside a growing clinical focus on the unique needs of older adults. In the past, the liver was not thought to undergo substantial age-related changes, nor was there thought to be any liver disease characteristic of older adults. Current studies challenge this perspective, revealing that ageing substantially influences liver pathophysiology at the organ level and within each of the liver cell types. These observations have implications for understanding the pathogenesis of liver diseases common in older adults, including hepatocellular carcinoma, hypoxic hepatitis and metabolic dysfunction-associated steatotic liver disease. Previously, managing older patients with liver disease mostly addressed age-related changes in drug metabolism and liver function tests. However, current clinical practice increasingly emphasizes age-specific issues such as frailty, sarcopenia, multimorbidity and polypharmacy. Given the liver’s pivotal role in systemic metabolism, immunity and detoxification, ageing of the liver can contribute to systemic diseases. In the future, interventions that target ageing biology might offer new treatment options for liver diseases. Here, we review those age-related changes in the liver that have substantial biological and clinical consequences for older adults. Older adults can be affected by multiple chronic medical conditions, including liver disease. This Review provides a comprehensive overview of age-related pathophysiological changes in the liver and discusses interventions and treatment options for older patients.
{"title":"Liver, ageing and disease","authors":"David G. Le Couteur, Meng C. Ngu, Nicholas J. Hunt, Amanda E. Brandon, Stephen J. Simpson, Victoria C. Cogger","doi":"10.1038/s41575-025-01099-z","DOIUrl":"10.1038/s41575-025-01099-z","url":null,"abstract":"As the global population ages, research on the biology of ageing and its role in chronic disease is expanding, alongside a growing clinical focus on the unique needs of older adults. In the past, the liver was not thought to undergo substantial age-related changes, nor was there thought to be any liver disease characteristic of older adults. Current studies challenge this perspective, revealing that ageing substantially influences liver pathophysiology at the organ level and within each of the liver cell types. These observations have implications for understanding the pathogenesis of liver diseases common in older adults, including hepatocellular carcinoma, hypoxic hepatitis and metabolic dysfunction-associated steatotic liver disease. Previously, managing older patients with liver disease mostly addressed age-related changes in drug metabolism and liver function tests. However, current clinical practice increasingly emphasizes age-specific issues such as frailty, sarcopenia, multimorbidity and polypharmacy. Given the liver’s pivotal role in systemic metabolism, immunity and detoxification, ageing of the liver can contribute to systemic diseases. In the future, interventions that target ageing biology might offer new treatment options for liver diseases. Here, we review those age-related changes in the liver that have substantial biological and clinical consequences for older adults. Older adults can be affected by multiple chronic medical conditions, including liver disease. This Review provides a comprehensive overview of age-related pathophysiological changes in the liver and discusses interventions and treatment options for older patients.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"22 10","pages":"680-695"},"PeriodicalIF":51.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144715321","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 : 2025-07-25DOI: 10.1038/s41575-025-01101-8
With just 5 years to go until the WHO’s goal to eliminate viral hepatitis as a public health threat by 2030, focus must turn to the inequitable access to testing and treatment across the world, and to breaking down the barriers that prevent viral hepatitis elimination.
{"title":"Viral hepatitis: breaking down barriers","authors":"","doi":"10.1038/s41575-025-01101-8","DOIUrl":"10.1038/s41575-025-01101-8","url":null,"abstract":"With just 5 years to go until the WHO’s goal to eliminate viral hepatitis as a public health threat by 2030, focus must turn to the inequitable access to testing and treatment across the world, and to breaking down the barriers that prevent viral hepatitis elimination.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"22 9","pages":"597-597"},"PeriodicalIF":51.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41575-025-01101-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144701541","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 : 2025-07-21DOI: 10.1038/s41575-025-01098-0
Chul S. Hyun, Sarah Soyeon Oh, Lawrence Wu, Ryan H. Moy, Jae Il Shin
Gastric cancer is often overlooked in the United States, yet East Asian and other immigrant communities face a markedly increased burden. A community-based, migration-informed approach is needed to strengthen prevention and reduce disparities.
{"title":"Rethinking gastric cancer prevention through an immigrant health lens","authors":"Chul S. Hyun, Sarah Soyeon Oh, Lawrence Wu, Ryan H. Moy, Jae Il Shin","doi":"10.1038/s41575-025-01098-0","DOIUrl":"10.1038/s41575-025-01098-0","url":null,"abstract":"Gastric cancer is often overlooked in the United States, yet East Asian and other immigrant communities face a markedly increased burden. A community-based, migration-informed approach is needed to strengthen prevention and reduce disparities.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"22 9","pages":"600-601"},"PeriodicalIF":51.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677460","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 : 2025-07-21DOI: 10.1038/s41575-025-01087-3
Folasade P. May, Winta T. Mehtsun, Ahmedin Jemal, Samir Gupta
Colorectal cancer (CRC) remains a substantial public health challenge globally and is the second leading cause of cancer-related death in the USA. Despite advances in screening and treatment, disparities in CRC outcomes persist, especially among Black individuals in the USA, who face higher CRC incidence and mortality and lower survival compared with White individuals. Inequities are largely attributed to social determinants of health (SDOH), such as access to health care, socioeconomic conditions and systemic inequities. In this Review, we examine Black–White disparities in CRC outcomes across the CRC care continuum in the USA, highlighting contributing modifiable (non-biological) and non-modifiable (biological) risk factors. We also discuss successful interventions that have reduced or eliminated disparities. Existing evidence suggests that Black–White differences in CRC screening participation, CRC incidence and CRC mortality can be resolved. Future efforts must emphasize improving access to screening and guideline-concordant treatment to achieve progress in the near term while addressing the underlying and historical SDOH that drive inequities to eliminate disparities in the long term. The Review underscores the need for sustained investment in addressing both immediate and systemic barriers to CRC screening and care in Black communities to eliminate disparities in CRC outcomes and improve the overall health of the nation. In the USA, colorectal cancer (CRC) is a leading cause of death and a public health challenge due to persisting disparities between Black and White individuals. This Review examines Black–White disparities in CRC outcomes, bringing health-care and systemic inequities into focus.
{"title":"Black–White disparities across the colorectal cancer care continuum in the USA","authors":"Folasade P. May, Winta T. Mehtsun, Ahmedin Jemal, Samir Gupta","doi":"10.1038/s41575-025-01087-3","DOIUrl":"10.1038/s41575-025-01087-3","url":null,"abstract":"Colorectal cancer (CRC) remains a substantial public health challenge globally and is the second leading cause of cancer-related death in the USA. Despite advances in screening and treatment, disparities in CRC outcomes persist, especially among Black individuals in the USA, who face higher CRC incidence and mortality and lower survival compared with White individuals. Inequities are largely attributed to social determinants of health (SDOH), such as access to health care, socioeconomic conditions and systemic inequities. In this Review, we examine Black–White disparities in CRC outcomes across the CRC care continuum in the USA, highlighting contributing modifiable (non-biological) and non-modifiable (biological) risk factors. We also discuss successful interventions that have reduced or eliminated disparities. Existing evidence suggests that Black–White differences in CRC screening participation, CRC incidence and CRC mortality can be resolved. Future efforts must emphasize improving access to screening and guideline-concordant treatment to achieve progress in the near term while addressing the underlying and historical SDOH that drive inequities to eliminate disparities in the long term. The Review underscores the need for sustained investment in addressing both immediate and systemic barriers to CRC screening and care in Black communities to eliminate disparities in CRC outcomes and improve the overall health of the nation. In the USA, colorectal cancer (CRC) is a leading cause of death and a public health challenge due to persisting disparities between Black and White individuals. This Review examines Black–White disparities in CRC outcomes, bringing health-care and systemic inequities into focus.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"22 9","pages":"603-618"},"PeriodicalIF":51.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677539","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 : 2025-07-18DOI: 10.1038/s41575-025-01097-1
Gilaad G. Kaplan
Inflammatory bowel disease (IBD) is a global condition that progresses through four epidemiologic stages: emergence, acceleration in incidence, compounding prevalence and prevalence equilibrium. Early industrialized countries are currently in the compounding prevalence stage before transitioning to the prevalence equilibrium stage, with >1% of their populations expected to live with IBD within the next decade. Prevalence equilibrium can be modelled using a health–illness–death compartment framework and partial differential equations to predict prevalence to 2045. Meanwhile, newly industrialized countries are projected to shift from accelerated incidence with low prevalence to compounding prevalence over the next two decades. This Perspective explores the global evolution of IBD through these epidemiologic stages, presenting a framework for disease prevention and innovative health-care strategies to address the critical challenges the global IBD community will face over the next 20 years. The global burden of inflammatory bowel disease (IBD) is shifting as countries transition through four epidemiologic stages. This Perspective explores the global evolution of IBD over the next 20 years and proposes strategies for prevention and health-care innovation.
{"title":"The global burden of inflammatory bowel disease: from 2025 to 2045","authors":"Gilaad G. Kaplan","doi":"10.1038/s41575-025-01097-1","DOIUrl":"10.1038/s41575-025-01097-1","url":null,"abstract":"Inflammatory bowel disease (IBD) is a global condition that progresses through four epidemiologic stages: emergence, acceleration in incidence, compounding prevalence and prevalence equilibrium. Early industrialized countries are currently in the compounding prevalence stage before transitioning to the prevalence equilibrium stage, with >1% of their populations expected to live with IBD within the next decade. Prevalence equilibrium can be modelled using a health–illness–death compartment framework and partial differential equations to predict prevalence to 2045. Meanwhile, newly industrialized countries are projected to shift from accelerated incidence with low prevalence to compounding prevalence over the next two decades. This Perspective explores the global evolution of IBD through these epidemiologic stages, presenting a framework for disease prevention and innovative health-care strategies to address the critical challenges the global IBD community will face over the next 20 years. The global burden of inflammatory bowel disease (IBD) is shifting as countries transition through four epidemiologic stages. This Perspective explores the global evolution of IBD over the next 20 years and proposes strategies for prevention and health-care innovation.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"22 10","pages":"708-720"},"PeriodicalIF":51.0,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41575-025-01097-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144652507","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 : 2025-07-07DOI: 10.1038/s41575-025-01089-1
Harry Cheuk-Hay Lau, Xiang Zhang, Jun Yu
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, affecting billions of the global population. It can gradually progress to more severe diseases, including steatohepatitis, cirrhosis and hepatocellular carcinoma. Studies have highlighted the importance of the gut microbiome in the pathogenesis and progression of MASLD. On the other hand, increasing evidence has revealed the clinical potential of targeting the gut microbiome to treat MASLD. In this Review, we summarize gut microbial alterations in MASLD, metabolic dysfunction-associated steatohepatitis and hepatocellular carcinoma. The mechanisms by which a dysregulated gut–liver axis contributes to disease progression are also described, including intestinal barrier dysfunction, chronic inflammation, and altered metabolic pathways (for example, bile acids) and microbial-derived metabolites (for example, short-chain fatty acids, tryptophan derivatives and endogenous ethanol). In addition, we discuss the clinical implications of utilizing the gut microbiome as a diagnostic biomarker and the therapeutic approaches to treat MASLD and related diseases such as faecal microbiota transplantation, probiotics and engineered bacteria, prebiotics and postbiotics, microbial-derived metabolites, antimicrobials and bacteriophages. Finally, we discuss current challenges in basic and translational research on the microbiome in MASLD and propose future directions to drive progress in this field. In this Review, Yu and colleagues describe the role of the gut microbiome and the gut–liver axis in metabolic dysfunction-associated steatotic liver disease (MASLD) and MASLD-related hepatocellular carcinoma (HCC). They discuss clinical implications for the diagnosis and treatment of MASLD and MASLD-related HCC.
{"title":"Gut microbiome in metabolic dysfunction-associated steatotic liver disease and associated hepatocellular carcinoma","authors":"Harry Cheuk-Hay Lau, Xiang Zhang, Jun Yu","doi":"10.1038/s41575-025-01089-1","DOIUrl":"10.1038/s41575-025-01089-1","url":null,"abstract":"Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, affecting billions of the global population. It can gradually progress to more severe diseases, including steatohepatitis, cirrhosis and hepatocellular carcinoma. Studies have highlighted the importance of the gut microbiome in the pathogenesis and progression of MASLD. On the other hand, increasing evidence has revealed the clinical potential of targeting the gut microbiome to treat MASLD. In this Review, we summarize gut microbial alterations in MASLD, metabolic dysfunction-associated steatohepatitis and hepatocellular carcinoma. The mechanisms by which a dysregulated gut–liver axis contributes to disease progression are also described, including intestinal barrier dysfunction, chronic inflammation, and altered metabolic pathways (for example, bile acids) and microbial-derived metabolites (for example, short-chain fatty acids, tryptophan derivatives and endogenous ethanol). In addition, we discuss the clinical implications of utilizing the gut microbiome as a diagnostic biomarker and the therapeutic approaches to treat MASLD and related diseases such as faecal microbiota transplantation, probiotics and engineered bacteria, prebiotics and postbiotics, microbial-derived metabolites, antimicrobials and bacteriophages. Finally, we discuss current challenges in basic and translational research on the microbiome in MASLD and propose future directions to drive progress in this field. In this Review, Yu and colleagues describe the role of the gut microbiome and the gut–liver axis in metabolic dysfunction-associated steatotic liver disease (MASLD) and MASLD-related hepatocellular carcinoma (HCC). They discuss clinical implications for the diagnosis and treatment of MASLD and MASLD-related HCC.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"22 9","pages":"619-638"},"PeriodicalIF":51.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568814","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 : 2025-07-02DOI: 10.1038/s41575-025-01092-6
Julius E. Brinck, Anurag K. Sinha, Martin F. Laursen, Lars O. Dragsted, Jeroen Raes, Ruben Vazquez Uribe, Jens Walter, Henrik M. Roager, Tine R. Licht
In the human gastrointestinal tract, pH is a key factor in shaping gut microbial composition and activity, while also being influenced by microbial metabolism. pH varies substantially along the gastrointestinal tract within an individual and between different individuals due to a combination of host, diet, microbial and external factors. The importance of pH on microbiota composition and metabolic response has been widely explored over the past century. Here, we review the literature to explore the major physiological and dietary factors that influence pH along the gastrointestinal tract. From a microbial ecology perspective, we discuss how gastrointestinal pH affects microbiota composition and metabolism. We explore mechanisms by which pH can influence bacterial acid response systems, gene expression and the production of microbial metabolites important for health. Finally, we review the literature regarding the potential role of gastrointestinal pH in human diseases. We propose that we can advance our understanding of the gut microbiota in health and disease by considering gastrointestinal pH. We argue that pH-mediated gut microbial metabolic variation is highly important for predicting and manipulating metabolic output relevant to human health. In humans, pH varies across the gastrointestinal tract. This Review provides an overview of gastrointestinal pH and its role in shaping the gut microbiota, highlighting major physiological and dietary factors that influence gastrointestinal pH and how in turn pH affects microbiota composition and metabolism in health and, potentially, disease.
{"title":"Intestinal pH: a major driver of human gut microbiota composition and metabolism","authors":"Julius E. Brinck, Anurag K. Sinha, Martin F. Laursen, Lars O. Dragsted, Jeroen Raes, Ruben Vazquez Uribe, Jens Walter, Henrik M. Roager, Tine R. Licht","doi":"10.1038/s41575-025-01092-6","DOIUrl":"10.1038/s41575-025-01092-6","url":null,"abstract":"In the human gastrointestinal tract, pH is a key factor in shaping gut microbial composition and activity, while also being influenced by microbial metabolism. pH varies substantially along the gastrointestinal tract within an individual and between different individuals due to a combination of host, diet, microbial and external factors. The importance of pH on microbiota composition and metabolic response has been widely explored over the past century. Here, we review the literature to explore the major physiological and dietary factors that influence pH along the gastrointestinal tract. From a microbial ecology perspective, we discuss how gastrointestinal pH affects microbiota composition and metabolism. We explore mechanisms by which pH can influence bacterial acid response systems, gene expression and the production of microbial metabolites important for health. Finally, we review the literature regarding the potential role of gastrointestinal pH in human diseases. We propose that we can advance our understanding of the gut microbiota in health and disease by considering gastrointestinal pH. We argue that pH-mediated gut microbial metabolic variation is highly important for predicting and manipulating metabolic output relevant to human health. In humans, pH varies across the gastrointestinal tract. This Review provides an overview of gastrointestinal pH and its role in shaping the gut microbiota, highlighting major physiological and dietary factors that influence gastrointestinal pH and how in turn pH affects microbiota composition and metabolism in health and, potentially, disease.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"22 9","pages":"639-656"},"PeriodicalIF":51.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546903","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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