Pub Date : 2024-02-14DOI: 10.1038/s41575-023-00890-0
María R. Aburto, John F. Cryan
Crosstalk between gut and brain has long been appreciated in health and disease, and the gut microbiota is a key player in communication between these two distant organs. Yet, the mechanisms through which the microbiota influences development and function of the gut–brain axis remain largely unknown. Barriers present in the gut and brain are specialized cellular interfaces that maintain strict homeostasis of different compartments across this axis. These barriers include the gut epithelial barrier, the blood–brain barrier and the blood–cerebrospinal fluid barrier. Barriers are ideally positioned to receive and communicate gut microbial signals constituting a gateway for gut–microbiota–brain communication. In this Review, we focus on how modulation of these barriers by the gut microbiota can constitute an important channel of communication across the gut–brain axis. Moreover, barrier malfunction upon alterations in gut microbial composition could form the basis of various conditions, including often comorbid neurological and gastrointestinal disorders. Thus, we should focus on unravelling the molecular and cellular basis of this communication and move from simplistic framing as ‘leaky gut’. A mechanistic understanding of gut microbiota modulation of barriers, especially during critical windows of development, could be key to understanding the aetiology of gastrointestinal and neurological disorders. The gut microbiota is an important modulator of the gut–brain axis. This Review provides an overview of barrier function across this axis and examines the role of the gut microbiota in communication across and between these specialized gastrointestinal and brain barriers in health and disease.
{"title":"Gastrointestinal and brain barriers: unlocking gates of communication across the microbiota–gut–brain axis","authors":"María R. Aburto, John F. Cryan","doi":"10.1038/s41575-023-00890-0","DOIUrl":"10.1038/s41575-023-00890-0","url":null,"abstract":"Crosstalk between gut and brain has long been appreciated in health and disease, and the gut microbiota is a key player in communication between these two distant organs. Yet, the mechanisms through which the microbiota influences development and function of the gut–brain axis remain largely unknown. Barriers present in the gut and brain are specialized cellular interfaces that maintain strict homeostasis of different compartments across this axis. These barriers include the gut epithelial barrier, the blood–brain barrier and the blood–cerebrospinal fluid barrier. Barriers are ideally positioned to receive and communicate gut microbial signals constituting a gateway for gut–microbiota–brain communication. In this Review, we focus on how modulation of these barriers by the gut microbiota can constitute an important channel of communication across the gut–brain axis. Moreover, barrier malfunction upon alterations in gut microbial composition could form the basis of various conditions, including often comorbid neurological and gastrointestinal disorders. Thus, we should focus on unravelling the molecular and cellular basis of this communication and move from simplistic framing as ‘leaky gut’. A mechanistic understanding of gut microbiota modulation of barriers, especially during critical windows of development, could be key to understanding the aetiology of gastrointestinal and neurological disorders. The gut microbiota is an important modulator of the gut–brain axis. This Review provides an overview of barrier function across this axis and examines the role of the gut microbiota in communication across and between these specialized gastrointestinal and brain barriers in health and disease.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":null,"pages":null},"PeriodicalIF":65.1,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41575-023-00890-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139735644","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 : 2024-02-12DOI: 10.1038/s41575-024-00904-5
Jordan Hindson
{"title":"Sintilimab as adjuvant therapy for patients with resected HCC at high risk of recurrence","authors":"Jordan Hindson","doi":"10.1038/s41575-024-00904-5","DOIUrl":"10.1038/s41575-024-00904-5","url":null,"abstract":"","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":null,"pages":null},"PeriodicalIF":65.1,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139720249","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 : 2024-02-12DOI: 10.1038/s41575-024-00905-4
Jordan Hindson
{"title":"HCV direct-acting antiviral therapy adherence in people who inject drugs","authors":"Jordan Hindson","doi":"10.1038/s41575-024-00905-4","DOIUrl":"10.1038/s41575-024-00905-4","url":null,"abstract":"","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":null,"pages":null},"PeriodicalIF":65.1,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139720216","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 : 2024-02-12DOI: 10.1038/s41575-024-00903-6
Jordan Hindson
{"title":"Linaclotide for functional constipation in paediatric patients: phase III results","authors":"Jordan Hindson","doi":"10.1038/s41575-024-00903-6","DOIUrl":"10.1038/s41575-024-00903-6","url":null,"abstract":"","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":null,"pages":null},"PeriodicalIF":65.1,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139720218","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 : 2024-02-09DOI: 10.1038/s41575-024-00898-0
William Gilmore, Ian Gilmore
A new study by Díaz and colleagues links strong alcohol policy with improved health and societal outcomes. The evidence for what works to reduce the enormous burden from alcohol is clear. The question is why are governments still not acting?
{"title":"Evidence-based alcohol policies are the answer","authors":"William Gilmore, Ian Gilmore","doi":"10.1038/s41575-024-00898-0","DOIUrl":"10.1038/s41575-024-00898-0","url":null,"abstract":"A new study by Díaz and colleagues links strong alcohol policy with improved health and societal outcomes. The evidence for what works to reduce the enormous burden from alcohol is clear. The question is why are governments still not acting?","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":null,"pages":null},"PeriodicalIF":65.1,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139710813","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 : 2024-02-09DOI: 10.1038/s41575-024-00895-3
Ludvig M. Sollid
Coeliac disease is an autoinflammatory condition caused by immune reactions to cereal gluten proteins. Currently, the only available treatment for the condition is a lifelong avoidance of gluten proteins in the diet. There is an unmet need for alternative therapies. Coeliac disease has a strong association with certain HLA−DQ allotypes (DQ2.5, DQ2.2 and DQ8), and these disease-associated HLA-DQ molecules present deamidated gluten peptides to gluten-specific CD4+ T cells. The gluten-specific CD4+ T cells are the drivers of the immune reactions leading to coeliac disease. Once established, the clonotypes of gluten-specific CD4+ T cells persist for decades, explaining why patients must adhere to a gluten-free diet for life. Given the key pathogenic role of gluten-specific CD4+ T cells, tolerance-inducing therapies that target these T cells are attractive for treatment of the disorder. Lessons learned from coeliac disease might provide clues for treatment of other HLA-associated diseases for which the disease-driving antigens are unknown. Thus, intensive efforts have been and are currently implemented to bring an effective tolerance-inducing therapy for coeliac disease. This Review discusses mechanisms of the various approaches taken, summarizing the progress made, and highlights future directions in this field. Coeliac disease is an autoinflammatory disease, with the only available treatment being a lifelong gluten-free diet. Alternative therapeutic approaches are needed. This Review explores the concept of tolerance-inducing therapies for coeliac disease, highlighting the underlying mechanisms, progress, challenges and future directions.
乳糜泻是一种由谷类麸质蛋白引起的免疫反应导致的自身炎症。目前，治疗这种疾病的唯一方法是终生避免在饮食中摄入麸质蛋白。替代疗法的需求尚未得到满足。乳糜泻与某些 HLA-DQ 异型（DQ2.5、DQ2.2 和 DQ8）密切相关，这些与疾病相关的 HLA-DQ 分子会向麸质特异性 CD4+ T 细胞展示脱氨麸质肽。麸质特异性 CD4+ T 细胞是导致乳糜泻的免疫反应的驱动力。麸质特异性 CD4+ T 细胞的克隆型一旦形成，就会持续数十年，这也解释了为什么患者必须终生坚持无麸质饮食。鉴于麸质特异性 CD4+ T 细胞的关键致病作用，针对这些 T 细胞的耐受诱导疗法对治疗这种疾病很有吸引力。从乳糜泻中汲取的经验教训可能会为治疗其他 HLA 相关疾病提供线索，因为这些疾病的致病抗原尚不清楚。因此，人们一直在努力为乳糜泻提供有效的耐受诱导疗法。本综述讨论了所采取的各种方法的机制，总结了所取得的进展，并强调了该领域未来的发展方向。
{"title":"Tolerance-inducing therapies in coeliac disease — mechanisms, progress and future directions","authors":"Ludvig M. Sollid","doi":"10.1038/s41575-024-00895-3","DOIUrl":"10.1038/s41575-024-00895-3","url":null,"abstract":"Coeliac disease is an autoinflammatory condition caused by immune reactions to cereal gluten proteins. Currently, the only available treatment for the condition is a lifelong avoidance of gluten proteins in the diet. There is an unmet need for alternative therapies. Coeliac disease has a strong association with certain HLA−DQ allotypes (DQ2.5, DQ2.2 and DQ8), and these disease-associated HLA-DQ molecules present deamidated gluten peptides to gluten-specific CD4+ T cells. The gluten-specific CD4+ T cells are the drivers of the immune reactions leading to coeliac disease. Once established, the clonotypes of gluten-specific CD4+ T cells persist for decades, explaining why patients must adhere to a gluten-free diet for life. Given the key pathogenic role of gluten-specific CD4+ T cells, tolerance-inducing therapies that target these T cells are attractive for treatment of the disorder. Lessons learned from coeliac disease might provide clues for treatment of other HLA-associated diseases for which the disease-driving antigens are unknown. Thus, intensive efforts have been and are currently implemented to bring an effective tolerance-inducing therapy for coeliac disease. This Review discusses mechanisms of the various approaches taken, summarizing the progress made, and highlights future directions in this field. Coeliac disease is an autoinflammatory disease, with the only available treatment being a lifelong gluten-free diet. Alternative therapeutic approaches are needed. This Review explores the concept of tolerance-inducing therapies for coeliac disease, highlighting the underlying mechanisms, progress, challenges and future directions.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":null,"pages":null},"PeriodicalIF":65.1,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139710792","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 : 2024-02-07DOI: 10.1038/s41575-023-00891-z
Edward C. Deehan, Valentin Mocanu, Karen L. Madsen
Obesity and metabolic syndrome represent a growing epidemic worldwide. Body weight is regulated through complex interactions between hormonal, neural and metabolic pathways and is influenced by numerous environmental factors. Imbalances between energy intake and expenditure can occur due to several factors, including alterations in eating behaviours, abnormal satiation and satiety, and low energy expenditure. The gut microbiota profoundly affects all aspects of energy homeostasis through diverse mechanisms involving effects on mucosal and systemic immune, hormonal and neural systems. The benefits of dietary fibre on metabolism and obesity have been demonstrated through mechanistic studies and clinical trials, but many questions remain as to how different fibres are best utilized in managing obesity. In this Review, we discuss the physiochemical properties of different fibres, current findings on how fibre and the gut microbiota interact to regulate body weight homeostasis, and knowledge gaps related to using dietary fibres as a complementary strategy. Precision medicine approaches that utilize baseline microbiota and clinical characteristics to predict individual responses to fibre supplementation represent a new paradigm with great potential to enhance weight management efficacy, but many challenges remain before these approaches can be fully implemented. Obesity and metabolic syndrome are two complex and multifactorial conditions. This Review provides a comprehensive overview of dietary fibres, discussing physiochemical properties, microbiota interactions and therapeutic interventions for body weight and insulin resistance regulation.
{"title":"Effects of dietary fibre on metabolic health and obesity","authors":"Edward C. Deehan, Valentin Mocanu, Karen L. Madsen","doi":"10.1038/s41575-023-00891-z","DOIUrl":"10.1038/s41575-023-00891-z","url":null,"abstract":"Obesity and metabolic syndrome represent a growing epidemic worldwide. Body weight is regulated through complex interactions between hormonal, neural and metabolic pathways and is influenced by numerous environmental factors. Imbalances between energy intake and expenditure can occur due to several factors, including alterations in eating behaviours, abnormal satiation and satiety, and low energy expenditure. The gut microbiota profoundly affects all aspects of energy homeostasis through diverse mechanisms involving effects on mucosal and systemic immune, hormonal and neural systems. The benefits of dietary fibre on metabolism and obesity have been demonstrated through mechanistic studies and clinical trials, but many questions remain as to how different fibres are best utilized in managing obesity. In this Review, we discuss the physiochemical properties of different fibres, current findings on how fibre and the gut microbiota interact to regulate body weight homeostasis, and knowledge gaps related to using dietary fibres as a complementary strategy. Precision medicine approaches that utilize baseline microbiota and clinical characteristics to predict individual responses to fibre supplementation represent a new paradigm with great potential to enhance weight management efficacy, but many challenges remain before these approaches can be fully implemented. Obesity and metabolic syndrome are two complex and multifactorial conditions. This Review provides a comprehensive overview of dietary fibres, discussing physiochemical properties, microbiota interactions and therapeutic interventions for body weight and insulin resistance regulation.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":null,"pages":null},"PeriodicalIF":65.1,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139702978","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 : 2024-02-07DOI: 10.1038/s41575-024-00902-7
The Editors of Nature Reviews Gastroenterology & Hepatology travel regularly to conferences to meet with the research community and keep up to date on the latest research and key trends in the field. Come and say hello!
{"title":"Connecting with the community","authors":"","doi":"10.1038/s41575-024-00902-7","DOIUrl":"10.1038/s41575-024-00902-7","url":null,"abstract":"The Editors of Nature Reviews Gastroenterology & Hepatology travel regularly to conferences to meet with the research community and keep up to date on the latest research and key trends in the field. Come and say hello!","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":null,"pages":null},"PeriodicalIF":65.1,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41575-024-00902-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139702977","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}
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