Pub Date : 2024-05-13DOI: 10.1038/s41575-024-00931-2
Parsa S. Haque, Neeraj Kapur, Terrence A. Barrett, Arianne L. Theiss
Mitochondria are dynamic organelles that function in cellular energy metabolism, intracellular and extracellular signalling, cellular fate and stress responses. Mitochondria of the intestinal epithelium, the cellular interface between self and enteric microbiota, have emerged as crucial in intestinal health. Mitochondrial dysfunction occurs in gastrointestinal diseases, including inflammatory bowel diseases and colorectal cancer. In this Review, we provide an overview of the current understanding of intestinal epithelial cell mitochondrial metabolism, function and signalling to affect tissue homeostasis, including gut microbiota composition. We also discuss mitochondrial-targeted therapeutics for inflammatory bowel diseases and colorectal cancer and the evolving concept of mitochondrial impairment as a consequence versus initiator of the disease. Mitochondria of the intestinal epithelium are vital in intestinal health and disease. This Review provides a comprehensive overview of intestinal epithelial cell mitochondrial dysfunction in inflammatory bowel diseases and colorectal cancer and discusses mitochondrial-targeted therapeutics for these diseases.
{"title":"Mitochondrial function and gastrointestinal diseases","authors":"Parsa S. Haque, Neeraj Kapur, Terrence A. Barrett, Arianne L. Theiss","doi":"10.1038/s41575-024-00931-2","DOIUrl":"10.1038/s41575-024-00931-2","url":null,"abstract":"Mitochondria are dynamic organelles that function in cellular energy metabolism, intracellular and extracellular signalling, cellular fate and stress responses. Mitochondria of the intestinal epithelium, the cellular interface between self and enteric microbiota, have emerged as crucial in intestinal health. Mitochondrial dysfunction occurs in gastrointestinal diseases, including inflammatory bowel diseases and colorectal cancer. In this Review, we provide an overview of the current understanding of intestinal epithelial cell mitochondrial metabolism, function and signalling to affect tissue homeostasis, including gut microbiota composition. We also discuss mitochondrial-targeted therapeutics for inflammatory bowel diseases and colorectal cancer and the evolving concept of mitochondrial impairment as a consequence versus initiator of the disease. Mitochondria of the intestinal epithelium are vital in intestinal health and disease. This Review provides a comprehensive overview of intestinal epithelial cell mitochondrial dysfunction in inflammatory bowel diseases and colorectal cancer and discusses mitochondrial-targeted therapeutics for these diseases.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":null,"pages":null},"PeriodicalIF":45.9,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140915142","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 : 2024-05-01DOI: 10.1038/s41575-024-00933-0
Sarah Singh, Nikki Duong, Laura Targownik, Sonali Paul, Christopher Vélez, Lauren D. Feld
Transgender and gender-diverse patients in the United States can have difficulty finding providers who are knowledgeable about their unique health-care needs. In many states, legislation limits the ability of physicians to provide gender-affirming and supportive care. Further awareness, advocacy and research is needed to help mitigate the discrimination and stigma endured by the transgender community.
{"title":"Transgender health care in the United States: legal, ethical and practical concerns for gastroenterologists in a changing landscape","authors":"Sarah Singh, Nikki Duong, Laura Targownik, Sonali Paul, Christopher Vélez, Lauren D. Feld","doi":"10.1038/s41575-024-00933-0","DOIUrl":"10.1038/s41575-024-00933-0","url":null,"abstract":"Transgender and gender-diverse patients in the United States can have difficulty finding providers who are knowledgeable about their unique health-care needs. In many states, legislation limits the ability of physicians to provide gender-affirming and supportive care. Further awareness, advocacy and research is needed to help mitigate the discrimination and stigma endured by the transgender community.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":null,"pages":null},"PeriodicalIF":65.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140817792","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 : 2024-04-25DOI: 10.1038/s41575-024-00920-5
Bo Shen
Pouchitis is an acute or chronic inflammatory disease of the ileal reservoir. It is common after restorative proctocolectomy with ileal pouch–anal anastomosis, and treatment of chronic antibiotic-refractory pouchitis has proven challenging. Most cases of acute pouchitis evolve into chronic pouchitis. The aetiology of acute pouchitis is likely to be partly related to the gut microbiota, whereas the pathophysiology of chronic pouchitis involves abnormal interactions between genetic disposition, faecal stasis, the gut microbiota, dysregulated host immunity, surgical techniques, ischaemia and mesentery-related factors. Pouchoscopy with biopsy is the most valuable modality for diagnosis, disease monitoring, assessment of treatment response, dysplasia surveillance and delivery of endoscopic therapy. Triggering or risk factors, such as Clostridioides difficile infection and use of non-steroidal anti-inflammatory drugs, should be modified or eradicated. In terms of treatment, acute pouchitis usually responds to oral antibiotics, whereas chronic antibiotic-refractory pouchitis often requires induction and maintenance therapy with integrin, interleukin or tumour necrosis factor inhibitors. Chronic pouchitis with ischaemic features, fistulae or abscesses can be treated with hyperbaric oxygen therapy. Pouchitis is a common condition that can occur after intestinal surgery. In this Review, Shen discusses our current understanding of the multifactorial pathophysiology, diagnosis and management of pouchitis, primarily in patients with underlying ulcerative colitis.
{"title":"Pouchitis: pathophysiology and management","authors":"Bo Shen","doi":"10.1038/s41575-024-00920-5","DOIUrl":"10.1038/s41575-024-00920-5","url":null,"abstract":"Pouchitis is an acute or chronic inflammatory disease of the ileal reservoir. It is common after restorative proctocolectomy with ileal pouch–anal anastomosis, and treatment of chronic antibiotic-refractory pouchitis has proven challenging. Most cases of acute pouchitis evolve into chronic pouchitis. The aetiology of acute pouchitis is likely to be partly related to the gut microbiota, whereas the pathophysiology of chronic pouchitis involves abnormal interactions between genetic disposition, faecal stasis, the gut microbiota, dysregulated host immunity, surgical techniques, ischaemia and mesentery-related factors. Pouchoscopy with biopsy is the most valuable modality for diagnosis, disease monitoring, assessment of treatment response, dysplasia surveillance and delivery of endoscopic therapy. Triggering or risk factors, such as Clostridioides difficile infection and use of non-steroidal anti-inflammatory drugs, should be modified or eradicated. In terms of treatment, acute pouchitis usually responds to oral antibiotics, whereas chronic antibiotic-refractory pouchitis often requires induction and maintenance therapy with integrin, interleukin or tumour necrosis factor inhibitors. Chronic pouchitis with ischaemic features, fistulae or abscesses can be treated with hyperbaric oxygen therapy. Pouchitis is a common condition that can occur after intestinal surgery. In this Review, Shen discusses our current understanding of the multifactorial pathophysiology, diagnosis and management of pouchitis, primarily in patients with underlying ulcerative colitis.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":null,"pages":null},"PeriodicalIF":45.9,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140648825","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 : 2024-04-23DOI: 10.1038/s41575-024-00915-2
Kylie P. Matchett, Jasmin Paris, Sarah A. Teichmann, Neil C. Henderson
Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly known as non-alcoholic fatty liver disease) is a leading cause of chronic liver disease worldwide. MASLD can progress to metabolic dysfunction-associated steatohepatitis (MASH, formerly known as non-alcoholic steatohepatitis) with subsequent liver cirrhosis and hepatocellular carcinoma formation. The advent of current technologies such as single-cell and single-nuclei RNA sequencing have transformed our understanding of the liver in homeostasis and disease. The next frontier is contextualizing this single-cell information in its native spatial orientation. This understanding will markedly accelerate discovery science in hepatology, resulting in a further step-change in our knowledge of liver biology and pathobiology. In this Review, we discuss up-to-date knowledge of MASLD development and progression and how the burgeoning field of spatial genomics is driving exciting new developments in our understanding of human liver disease pathogenesis and therapeutic target identification. This Perspective discusses single-cell and single-nuclei RNA sequencing in metabolic dysfunction-associated steatotic liver disease and explains how our understanding of the pathology of the disease will accelerate following the advances in spatial transcriptomics.
{"title":"Spatial genomics: mapping human steatotic liver disease","authors":"Kylie P. Matchett, Jasmin Paris, Sarah A. Teichmann, Neil C. Henderson","doi":"10.1038/s41575-024-00915-2","DOIUrl":"10.1038/s41575-024-00915-2","url":null,"abstract":"Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly known as non-alcoholic fatty liver disease) is a leading cause of chronic liver disease worldwide. MASLD can progress to metabolic dysfunction-associated steatohepatitis (MASH, formerly known as non-alcoholic steatohepatitis) with subsequent liver cirrhosis and hepatocellular carcinoma formation. The advent of current technologies such as single-cell and single-nuclei RNA sequencing have transformed our understanding of the liver in homeostasis and disease. The next frontier is contextualizing this single-cell information in its native spatial orientation. This understanding will markedly accelerate discovery science in hepatology, resulting in a further step-change in our knowledge of liver biology and pathobiology. In this Review, we discuss up-to-date knowledge of MASLD development and progression and how the burgeoning field of spatial genomics is driving exciting new developments in our understanding of human liver disease pathogenesis and therapeutic target identification. This Perspective discusses single-cell and single-nuclei RNA sequencing in metabolic dysfunction-associated steatotic liver disease and explains how our understanding of the pathology of the disease will accelerate following the advances in spatial transcriptomics.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":null,"pages":null},"PeriodicalIF":45.9,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140636445","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 : 2024-04-16DOI: 10.1038/s41575-024-00919-y
Julien Calderaro, Laura Žigutytė, Daniel Truhn, Ariel Jaffe, Jakob Nikolas Kather
Liver cancer has high incidence and mortality globally. Artificial intelligence (AI) has advanced rapidly, influencing cancer care. AI systems are already approved for clinical use in some tumour types (for example, colorectal cancer screening). Crucially, research demonstrates that AI can analyse histopathology, radiology and natural language in liver cancer, and can replace manual tasks and access hidden information in routinely available clinical data. However, for liver cancer, few of these applications have translated into large-scale clinical trials or clinically approved products. Here, we advocate for the incorporation of AI in all stages of liver cancer management. We present a taxonomy of AI approaches in liver cancer, highlighting areas with academic and commercial potential, and outline a policy for AI-based liver cancer management, including interdisciplinary training of researchers, clinicians and patients. The potential of AI in liver cancer is immense, but effort is required to ensure that AI can fulfil expectations. Artificial intelligence (AI) is advancing rapidly and is already starting to transform cancer research and care. Here, the authors outline how AI could be incorporated into liver cancer management, highlighting areas with academic, commercial and clinical potential, as well as ongoing progress and pitfalls.
{"title":"Artificial intelligence in liver cancer — new tools for research and patient management","authors":"Julien Calderaro, Laura Žigutytė, Daniel Truhn, Ariel Jaffe, Jakob Nikolas Kather","doi":"10.1038/s41575-024-00919-y","DOIUrl":"10.1038/s41575-024-00919-y","url":null,"abstract":"Liver cancer has high incidence and mortality globally. Artificial intelligence (AI) has advanced rapidly, influencing cancer care. AI systems are already approved for clinical use in some tumour types (for example, colorectal cancer screening). Crucially, research demonstrates that AI can analyse histopathology, radiology and natural language in liver cancer, and can replace manual tasks and access hidden information in routinely available clinical data. However, for liver cancer, few of these applications have translated into large-scale clinical trials or clinically approved products. Here, we advocate for the incorporation of AI in all stages of liver cancer management. We present a taxonomy of AI approaches in liver cancer, highlighting areas with academic and commercial potential, and outline a policy for AI-based liver cancer management, including interdisciplinary training of researchers, clinicians and patients. The potential of AI in liver cancer is immense, but effort is required to ensure that AI can fulfil expectations. Artificial intelligence (AI) is advancing rapidly and is already starting to transform cancer research and care. Here, the authors outline how AI could be incorporated into liver cancer management, highlighting areas with academic, commercial and clinical potential, as well as ongoing progress and pitfalls.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":null,"pages":null},"PeriodicalIF":45.9,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41575-024-00919-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140556825","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 : 2024-04-05DOI: 10.1038/s41575-024-00928-x
Daniel J. Huynh, Sonali Paul, Nikki Duong
The lesbian, gay, bisexual, transgender, queer, intersex and asexual (LGBTQIA+) community navigates a complex social landscape marked by strides in acceptance alongside enduring discrimination. Allies — individuals outside of the LGBTQIA+ spectrum who support and advocate for this community — are paramount, with allyship playing a critical part in influencing the health and well-being of LGBTQIA+ individuals.
{"title":"Promoting allyship to support and uplift the LGBTQIA+ community","authors":"Daniel J. Huynh, Sonali Paul, Nikki Duong","doi":"10.1038/s41575-024-00928-x","DOIUrl":"10.1038/s41575-024-00928-x","url":null,"abstract":"The lesbian, gay, bisexual, transgender, queer, intersex and asexual (LGBTQIA+) community navigates a complex social landscape marked by strides in acceptance alongside enduring discrimination. Allies — individuals outside of the LGBTQIA+ spectrum who support and advocate for this community — are paramount, with allyship playing a critical part in influencing the health and well-being of LGBTQIA+ individuals.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":null,"pages":null},"PeriodicalIF":65.1,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140349607","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 : 2024-04-04DOI: 10.1038/s41575-024-00914-3
Ipsita Mohanty, Celeste Allaband, Helena Mannochio-Russo, Yasin El Abiead, Lee R. Hagey, Rob Knight, Pieter C. Dorrestein
Bile acids regulate nutrient absorption and mitochondrial function, they establish and maintain gut microbial community composition and mediate inflammation, and they serve as signalling molecules that regulate appetite and energy homeostasis. The observation that there are hundreds of bile acids, especially many amidated bile acids, necessitates a revision of many of the classical descriptions of bile acids and bile acid enzyme functions. For example, bile salt hydrolases also have transferase activity. There are now hundreds of known modifications to bile acids and thousands of bile acid-associated genes, especially when including the microbiome, distributed throughout the human body (for example, there are >2,400 bile salt hydrolases alone). The fact that so much of our genetic and small-molecule repertoire, in both amount and diversity, is dedicated to bile acid function highlights the centrality of bile acids as key regulators of metabolism and immune homeostasis, which is, in large part, communicated via the gut microbiome. Bile acids have important roles in human metabolism and immune regulation. In this Perspective, Dorrestein and colleagues discuss the technologies and data science-related approaches that are improving our understanding of the diversity of bile acids and their multifaceted roles.
{"title":"The changing metabolic landscape of bile acids – keys to metabolism and immune regulation","authors":"Ipsita Mohanty, Celeste Allaband, Helena Mannochio-Russo, Yasin El Abiead, Lee R. Hagey, Rob Knight, Pieter C. Dorrestein","doi":"10.1038/s41575-024-00914-3","DOIUrl":"10.1038/s41575-024-00914-3","url":null,"abstract":"Bile acids regulate nutrient absorption and mitochondrial function, they establish and maintain gut microbial community composition and mediate inflammation, and they serve as signalling molecules that regulate appetite and energy homeostasis. The observation that there are hundreds of bile acids, especially many amidated bile acids, necessitates a revision of many of the classical descriptions of bile acids and bile acid enzyme functions. For example, bile salt hydrolases also have transferase activity. There are now hundreds of known modifications to bile acids and thousands of bile acid-associated genes, especially when including the microbiome, distributed throughout the human body (for example, there are >2,400 bile salt hydrolases alone). The fact that so much of our genetic and small-molecule repertoire, in both amount and diversity, is dedicated to bile acid function highlights the centrality of bile acids as key regulators of metabolism and immune homeostasis, which is, in large part, communicated via the gut microbiome. Bile acids have important roles in human metabolism and immune regulation. In this Perspective, Dorrestein and colleagues discuss the technologies and data science-related approaches that are improving our understanding of the diversity of bile acids and their multifaceted roles.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":null,"pages":null},"PeriodicalIF":45.9,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140346182","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 : 2024-04-04DOI: 10.1038/s41575-024-00929-w
María R. Aburto, John F. Cryan
{"title":"Publisher Correction: Gastrointestinal and brain barriers: unlocking gates of communication across the microbiota–gut–brain axis","authors":"María R. Aburto, John F. Cryan","doi":"10.1038/s41575-024-00929-w","DOIUrl":"10.1038/s41575-024-00929-w","url":null,"abstract":"","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":null,"pages":null},"PeriodicalIF":65.1,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41575-024-00929-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140814314","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 : 2024-04-02DOI: 10.1038/s41575-024-00927-y
Newsha Nikzad, Nikki Duong, Sonali Paul
Cultural safety seeks to remediate health inequities through empowering marginalized and minoritized patient populations, minimizing implicit bias and incorporating social determinants of health into practice. Here, we propose a cultural safety framework to guide communication with patients from sexual and gender minorities.
{"title":"Improving culturally safe engagement with sexual and gender minority populations","authors":"Newsha Nikzad, Nikki Duong, Sonali Paul","doi":"10.1038/s41575-024-00927-y","DOIUrl":"10.1038/s41575-024-00927-y","url":null,"abstract":"Cultural safety seeks to remediate health inequities through empowering marginalized and minoritized patient populations, minimizing implicit bias and incorporating social determinants of health into practice. Here, we propose a cultural safety framework to guide communication with patients from sexual and gender minorities.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":null,"pages":null},"PeriodicalIF":65.1,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140340781","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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