{"title":"Viral hepatitis: breaking down barriers","authors":"","doi":"10.1038/s41575-025-01101-8","DOIUrl":"https://doi.org/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":"20 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nutrient sensing and small intestinal enteric neurons","authors":"Katrina Ray","doi":"10.1038/s41575-025-01105-4","DOIUrl":"https://doi.org/10.1038/s41575-025-01105-4","url":null,"abstract":"<p>Different nutrients activate a distinct combination of enteric neurons in the small intestine, according to new research published in <i>Nature</i>. The findings add to our understanding of how the luminal environment in the gut can induce physiological responses.</p><p>The researchers used calcium imaging to identify and trace specific pathways of enteric neurons that are activated in response to different luminal nutrients applied to the mouse jejunum. Enteric nervous system activity was recorded in response to mucosal stimuli ex vivo and in vivo in mice. Crucially, different nutrients (glucose, acetate, <span>l</span>-phenylalanine as a model sugar, short-chain fatty acid and amino acid, respectively) activated distinct ensembles of myenteric and submucosal neurons. The nutrients (that is, chemically distinct signals) were detected by epithelial cells, which then, via a serotonin-mediated signalling process, led to enteric neuron activation. Interestingly, there was a spatial distribution of this luminal information relay along the radial axis of the intestine, such that some signals that originated from the intestinal villi are transmitted first to neurons in the outer myenteric plexus and then back to the inner submucosal plexus. Further work is needed to decipher the full extent of neuronal activation to downstream neurons (enteric interneurons and motor neurons) and extrinsic nerves beyond the initial stimulation site.</p>","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"19 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694050","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}
Chul S. Hyun, Sarah Soyeon Oh, Lawrence Wu, Ryan H. Moy, Jae Il Shin
{"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":"https://doi.org/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":"115 1","pages":""},"PeriodicalIF":65.1,"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}
Folasade P. May, Winta T. Mehtsun, Ahmedin Jemal, Samir Gupta
{"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":"https://doi.org/10.1038/s41575-025-01087-3","url":null,"abstract":"<p>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.</p>","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"675 1","pages":""},"PeriodicalIF":65.1,"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}
{"title":"The global burden of inflammatory bowel disease: from 2025 to 2045","authors":"Gilaad G. Kaplan","doi":"10.1038/s41575-025-01097-1","DOIUrl":"https://doi.org/10.1038/s41575-025-01097-1","url":null,"abstract":"<p>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.</p>","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"206 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"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":"https://doi.org/10.1038/s41575-025-01089-1","url":null,"abstract":"<p>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.</p>","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"108 1","pages":""},"PeriodicalIF":65.1,"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}
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
{"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":"https://doi.org/10.1038/s41575-025-01092-6","url":null,"abstract":"<p>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.</p>","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"28 1","pages":""},"PeriodicalIF":65.1,"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}
{"title":"Lessons from incretin-based therapy in MASH and obesity","authors":"Herbert Tilg, Giovanni Targher","doi":"10.1038/s41575-025-01096-2","DOIUrl":"https://doi.org/10.1038/s41575-025-01096-2","url":null,"abstract":"Glucagon-like peptide 1 receptor agonists are effective pharmacotherapies for the treatment of obesity and related disorders. In metabolic dysfunction-associated steatohepatitis with moderate to advanced fibrosis, semaglutide improved liver histology over 72 weeks. In another new study, tirzepatide was superior to semaglutide in reducing body weight in individuals with obesity.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"57 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500725","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}
{"title":"Pregnancy and liver health: delivering new collaborations to advance the MASLD and MASH field","authors":"Luiza Borges Manna, Caroline Ovadia","doi":"10.1038/s41575-025-01094-4","DOIUrl":"https://doi.org/10.1038/s41575-025-01094-4","url":null,"abstract":"<p>We read with great interest the article by Allen et al. (Envisioning how to advance the MASH field. <i>Nat. Rev. Gastroenterol. Hepatol</i>. <b>21</b>, 726–738 (2024))<sup>1</sup>, and particularly welcomed the acknowledgement of the intrauterine environment’s contribution to metabolic dysfunction-associated steatotic liver disease (MASLD; formerly known as nonalcoholic fatty liver disease) development in the offspring. The concept of the Developmental Origins of Health and Disease, pioneered by David Barker in 1986 (ref. <sup>2</sup>), highlights pregnancy as a valuable period to influence public health by addressing the intergenerational effect of non-communicable diseases, and it is highly fitting that MASLD is now recognized in this paradigm. But perhaps it is time to shine a brighter spotlight on pregnancy as a tool to advance the MASLD public health agenda.</p><p>In addition to offering insights into future offspring disease, pregnancy events can be used to predict long-term maternal outcomes. The International Federation of Gynecology and Obstetrics has emphasized the value of using pregnancy as a screening tool for a range of conditions<sup>3</sup>, highlighting the immediate postpartum period as an important window for early preventive interventions<sup>4</sup>. The antenatal period, often the first regular point of contact with healthcare professionals, also offers a unique triad of opportunity composed of engagement, motivation and receptivity to healthcare advice. Although this concept has mostly been applied to subsequent cardiovascular disease and type 2 diabetes<sup>5</sup>, evidence suggests that it is equally relevant to the field of MASLD. For instance, literature demonstrates that women affected by gestational diabetes are 50% more likely to develop MASLD within 16 months to 25 years of pregnancy than those without<sup>6</sup>. Although a causal relationship has not been confirmed, it is important to consider whether the metabolic challenges of pregnancy and associated dyslipidaemia, exacerbated by certain gestational disorders, could trigger or accelerate the pathway towards MASLD and metabolic dysfunction-associated steatohepatitis (MASH; formerly known as nonalcoholic steatohepatitis).</p>","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"46 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500726","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}
{"title":"Reply to ‘Pregnancy and liver health: delivering new collaborations to advance the MASLD and MASH field’","authors":"Alina M. Allen, Jeffrey V. Lazarus","doi":"10.1038/s41575-025-01095-3","DOIUrl":"https://doi.org/10.1038/s41575-025-01095-3","url":null,"abstract":"<p>We thank Borges Manna and Ovadia for their comments on our recent Perspective (Envisioning how to advance the MASH field. <i>Nat. Rev. Gastroenterol. Hepatol</i>. <b>21</b>, 726–738 (2024))<sup>1</sup> and for highlighting the importance of including pregnancy as a lens through which to further the MASLD public health agenda (Pregnancy and liver health: delivering new collaborations to advance the MASLD and MASH field. <i>Nat. Rev. Gastroenterol. Hepatol</i>. https://doi.org/10.1038/s41575-025-01094-4 (2025))<sup>2</sup>.</p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly known as nonalcoholic fatty liver disease)<sup>3</sup> is now the leading cause of end-stage liver disease requiring liver transplantation in women<sup>4</sup>. Owing to its slow progression, early identification — potentially decades before complications arise — presents a critical opportunity for timely intervention to prevent cirrhosis, adverse outcomes and mortality. Though rare, cirrhosis in pregnancy worsens fetal outcomes<sup>5</sup>. Antenatal and postpartum periods present ideal windows for early detection.</p>","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"80 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500724","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}