Pub Date : 2024-10-23DOI: 10.1038/s41575-024-01000-4
Bahtiyar Yilmaz, Andrew J. Macpherson
The small intestinal microbiota has a crucial role in gastrointestinal health, affecting digestion, immune function, bile acid homeostasis and nutrient metabolism. The challenges of accessibility at this site mean that our knowledge of the small intestinal microbiota is less developed than of the colonic or faecal microbiota. Here, we summarize the features and fluctuations of the microbiota along the small intestinal tract, focusing on humans, and discuss physicochemical factors and assessment methods, including the technical challenges of investigating the low microbial biomass of the proximal small bowel. We highlight the essential protective mechanisms of the small intestine, including motility, the paracellular barrier and mucus, and secretory immunity, to show their roles in limiting excessive exposure of host tissues to microbial metabolites. We address current knowledge gaps, particularly the variability among individuals, the effects of dysbiosis of the small intestinal microbiota on health and how different taxa in small intestinal microbiota could compensate for each other functionally. The small intestinal microbiota has a key influence on digestion, immunity and nutrient metabolism but is poorly understood in comparison with the faecal and colonic microbiota. This Perspective discusses the features of the small intestinal microbiota, highlighting technical challenges, knowledge gaps and implications for health.
{"title":"Delving the depths of ‘terra incognita’ in the human intestine — the small intestinal microbiota","authors":"Bahtiyar Yilmaz, Andrew J. Macpherson","doi":"10.1038/s41575-024-01000-4","DOIUrl":"10.1038/s41575-024-01000-4","url":null,"abstract":"The small intestinal microbiota has a crucial role in gastrointestinal health, affecting digestion, immune function, bile acid homeostasis and nutrient metabolism. The challenges of accessibility at this site mean that our knowledge of the small intestinal microbiota is less developed than of the colonic or faecal microbiota. Here, we summarize the features and fluctuations of the microbiota along the small intestinal tract, focusing on humans, and discuss physicochemical factors and assessment methods, including the technical challenges of investigating the low microbial biomass of the proximal small bowel. We highlight the essential protective mechanisms of the small intestine, including motility, the paracellular barrier and mucus, and secretory immunity, to show their roles in limiting excessive exposure of host tissues to microbial metabolites. We address current knowledge gaps, particularly the variability among individuals, the effects of dysbiosis of the small intestinal microbiota on health and how different taxa in small intestinal microbiota could compensate for each other functionally. The small intestinal microbiota has a key influence on digestion, immunity and nutrient metabolism but is poorly understood in comparison with the faecal and colonic microbiota. This Perspective discusses the features of the small intestinal microbiota, highlighting technical challenges, knowledge gaps and implications for health.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"22 1","pages":"71-81"},"PeriodicalIF":45.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487841","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 : 2024-10-17DOI: 10.1038/s41575-024-00991-4
Rohit A. Sinha, Eveline Bruinstroop, Paul M. Yen
Thyroid hormones (triiodothyronine and thyroxine) are pivotal for metabolic balance in the liver and entire body. Dysregulation of the hypothalamus–pituitary–thyroid axis can contribute to hepatic metabolic disturbances, affecting lipid metabolism, glucose regulation and protein synthesis. In addition, reductions in circulating and intrahepatic thyroid hormone concentrations increase the risk of metabolic dysfunction-associated steatotic liver disease by inducing lipotoxicity, inflammation and fibrosis. Amelioration of hepatic metabolic disease by thyroid hormones in preclinical and clinical studies has spurred the development of thyromimetics that target THRB (the predominant thyroid hormone receptor isoform in the liver) and/or the liver itself to provide more selective activation of hepatic thyroid hormone-regulated metabolic pathways while reducing thyrotoxic side effects in tissues that predominantly express THRA such as the heart and bone. Resmetirom, a liver and THRB-selective thyromimetic, recently became the first FDA-approved drug for metabolic dysfunction-associated steatohepatitis (MASH). Thus, a better understanding of the metabolic actions of thyroid hormones and thyromimetics in the liver is timely and clinically relevant. Here, we describe the roles of thyroid hormones in normal liver function and pathogenesis of MASH, as well as some potential clinical issues that might arise when treating patients with MASH with thyroid hormone supplementation or thyromimetics. Thyroid hormones, triiodothyronine and thyroxine, are vital for metabolic homeostasis, and regulate essential hepatic functions. This Review summarizes the current knowledge of the role of thyroid hormones in the liver and examines the development of thyromimetics for liver disease.
{"title":"Actions of thyroid hormones and thyromimetics on the liver","authors":"Rohit A. Sinha, Eveline Bruinstroop, Paul M. Yen","doi":"10.1038/s41575-024-00991-4","DOIUrl":"10.1038/s41575-024-00991-4","url":null,"abstract":"Thyroid hormones (triiodothyronine and thyroxine) are pivotal for metabolic balance in the liver and entire body. Dysregulation of the hypothalamus–pituitary–thyroid axis can contribute to hepatic metabolic disturbances, affecting lipid metabolism, glucose regulation and protein synthesis. In addition, reductions in circulating and intrahepatic thyroid hormone concentrations increase the risk of metabolic dysfunction-associated steatotic liver disease by inducing lipotoxicity, inflammation and fibrosis. Amelioration of hepatic metabolic disease by thyroid hormones in preclinical and clinical studies has spurred the development of thyromimetics that target THRB (the predominant thyroid hormone receptor isoform in the liver) and/or the liver itself to provide more selective activation of hepatic thyroid hormone-regulated metabolic pathways while reducing thyrotoxic side effects in tissues that predominantly express THRA such as the heart and bone. Resmetirom, a liver and THRB-selective thyromimetic, recently became the first FDA-approved drug for metabolic dysfunction-associated steatohepatitis (MASH). Thus, a better understanding of the metabolic actions of thyroid hormones and thyromimetics in the liver is timely and clinically relevant. Here, we describe the roles of thyroid hormones in normal liver function and pathogenesis of MASH, as well as some potential clinical issues that might arise when treating patients with MASH with thyroid hormone supplementation or thyromimetics. Thyroid hormones, triiodothyronine and thyroxine, are vital for metabolic homeostasis, and regulate essential hepatic functions. This Review summarizes the current knowledge of the role of thyroid hormones in the liver and examines the development of thyromimetics for liver disease.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"22 1","pages":"9-22"},"PeriodicalIF":45.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448256","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 : 2024-10-15DOI: 10.1038/s41575-024-01010-2
Eleni Kotsiliti
{"title":"Liraglutide treatment in children with obesity","authors":"Eleni Kotsiliti","doi":"10.1038/s41575-024-01010-2","DOIUrl":"10.1038/s41575-024-01010-2","url":null,"abstract":"","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 12","pages":"829-829"},"PeriodicalIF":45.9,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435977","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 : 2024-10-14DOI: 10.1038/s41575-024-00995-0
Katie Witkiewitz, Jessica L. Mellinger, Brian P. Lee, Srinivasan Dasarathy, Laura E. Nagy, Mack C. Mitchell
{"title":"Reply to ‘An expert panel Consensus Statement on ALD without experts by experience’","authors":"Katie Witkiewitz, Jessica L. Mellinger, Brian P. Lee, Srinivasan Dasarathy, Laura E. Nagy, Mack C. Mitchell","doi":"10.1038/s41575-024-00995-0","DOIUrl":"10.1038/s41575-024-00995-0","url":null,"abstract":"","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 12","pages":"886-886"},"PeriodicalIF":45.9,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41575-024-00995-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431131","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 : 2024-10-11DOI: 10.1038/s41575-024-00998-x
Elena Campello, Luca Fabris, Paolo Simioni
Management of anticoagulation in cirrhosis is challenging because of the concomitant risk of both thromboembolism and bleeding complications. Randomized controlled studies are lacking. Direct oral anticoagulants seem to be the most manageable option. However, for patients with Child C cirrhosis, the only safer anticoagulant strategy, currently, is low-molecular-weight heparin.
肝硬化患者的抗凝管理具有挑战性，因为同时存在血栓栓塞和出血并发症的风险。目前尚缺乏随机对照研究。直接口服抗凝剂似乎是最易控制的选择。然而，对于 Child C 肝硬化患者来说，目前唯一比较安全的抗凝策略是低分子量肝素。
{"title":"Anticoagulants in cirrhosis: main concerns","authors":"Elena Campello, Luca Fabris, Paolo Simioni","doi":"10.1038/s41575-024-00998-x","DOIUrl":"10.1038/s41575-024-00998-x","url":null,"abstract":"Management of anticoagulation in cirrhosis is challenging because of the concomitant risk of both thromboembolism and bleeding complications. Randomized controlled studies are lacking. Direct oral anticoagulants seem to be the most manageable option. However, for patients with Child C cirrhosis, the only safer anticoagulant strategy, currently, is low-molecular-weight heparin.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 12","pages":"827-828"},"PeriodicalIF":45.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142404907","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 : 2024-10-09DOI: 10.1038/s41575-024-00992-3
Brian Johnson, Kit Curtius
Digital twins provide a framework to advance the field of personalized medicine by generating clinically actionable strategies that leverage individualized data as well as current and emerging research. Strong interdisciplinary teamwork, specific funding mechanisms and integration of key biological details such as somatic evolution are necessary for the effective adoption of digital twins in medicine.
{"title":"Digital twins are integral to personalizing medicine and improving public health","authors":"Brian Johnson, Kit Curtius","doi":"10.1038/s41575-024-00992-3","DOIUrl":"10.1038/s41575-024-00992-3","url":null,"abstract":"Digital twins provide a framework to advance the field of personalized medicine by generating clinically actionable strategies that leverage individualized data as well as current and emerging research. Strong interdisciplinary teamwork, specific funding mechanisms and integration of key biological details such as somatic evolution are necessary for the effective adoption of digital twins in medicine.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 11","pages":"740-741"},"PeriodicalIF":45.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385079","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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