Interorgan and Transcellular Communication in Metabolic Disease: Insights From Recent CMGH Studies

The emergence of interorgan and transcellular signaling as a defining hallmark of metabolic disease has catalyzed a paradigm shift in gastroenterology and hepatology. Increasingly, the gut, liver, adipose tissue, immune system, and the nervous system are being understood as nodes in an integrated me...

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Main Authors: Tien S. Dong, Emeran Mayer
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Cellular and Molecular Gastroenterology and Hepatology
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Online Access:http://www.sciencedirect.com/science/article/pii/S2352345X25000712
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author Tien S. Dong
Emeran Mayer
author_facet Tien S. Dong
Emeran Mayer
author_sort Tien S. Dong
collection DOAJ
description The emergence of interorgan and transcellular signaling as a defining hallmark of metabolic disease has catalyzed a paradigm shift in gastroenterology and hepatology. Increasingly, the gut, liver, adipose tissue, immune system, and the nervous system are being understood as nodes in an integrated metabolic network rather than isolated organs. The gut microbiome and its metabolites, enteroendocrine signaling, bile acid regulation, and epithelial barrier functions now occupy center stage in dissecting the pathophysiology not only of gastroenterologic conditions, such as obesity, metabolic dysfunction-associated steatotic liver disease, and cirrhosis, but also of several disorders making up the chronic noncontagious disease epidemic.This paradigm shift is being driven by advances in molecular biology, systems biology, and computational modeling, which have enabled a holistic understanding of how communication between organs orchestrates metabolic homeostasis.1 Key to this understanding is the realization that local perturbations in 1 organ, such as gut microbial dysbiosis, can have systemic repercussions that affect distant organs, such as the liver or brain.2,3 This has redefined how researchers conceptualize disease progression and therapeutic interventions. Rather than focusing on a single tissue, there is increasing interest in identifying molecular messengers that mediate crosstalk between organ systems, such as microbial metabolites, enteroendocrine peptides, bile acids, and cytokines.In this review, we highlight 4 recent and impactful studies published in Cellular and Molecular Gastroenterology and Hepatology that exemplify these advances. Each study offers a unique window into the mechanisms by which gut-derived signals influence host metabolism and disease states. Together, they deepen the understanding of the complex dialogue between organs and open new avenues for therapeutic exploration. We conclude by discussing the implications of these findings and outlining emerging questions and future directions for the field.
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spelling doaj-art-7b6e0d1c9cfd49d2b4dc8a22ff8c77312025-08-20T03:31:06ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2025-01-0119810153010.1016/j.jcmgh.2025.101530Interorgan and Transcellular Communication in Metabolic Disease: Insights From Recent CMGH StudiesTien S. Dong0Emeran Mayer1Goodman-Luskin Microbiome Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; Oppenheimer Center for Neurobiology of Stress and Reslience, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; The Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CaliforniaGoodman-Luskin Microbiome Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; Oppenheimer Center for Neurobiology of Stress and Reslience, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; The Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; Address correspondence to: Emeran Mayer, MD, Medicine, 10833 Le Conte Ave, CHS 42-210, MC 737818, Los Angeles, California 90095.The emergence of interorgan and transcellular signaling as a defining hallmark of metabolic disease has catalyzed a paradigm shift in gastroenterology and hepatology. Increasingly, the gut, liver, adipose tissue, immune system, and the nervous system are being understood as nodes in an integrated metabolic network rather than isolated organs. The gut microbiome and its metabolites, enteroendocrine signaling, bile acid regulation, and epithelial barrier functions now occupy center stage in dissecting the pathophysiology not only of gastroenterologic conditions, such as obesity, metabolic dysfunction-associated steatotic liver disease, and cirrhosis, but also of several disorders making up the chronic noncontagious disease epidemic.This paradigm shift is being driven by advances in molecular biology, systems biology, and computational modeling, which have enabled a holistic understanding of how communication between organs orchestrates metabolic homeostasis.1 Key to this understanding is the realization that local perturbations in 1 organ, such as gut microbial dysbiosis, can have systemic repercussions that affect distant organs, such as the liver or brain.2,3 This has redefined how researchers conceptualize disease progression and therapeutic interventions. Rather than focusing on a single tissue, there is increasing interest in identifying molecular messengers that mediate crosstalk between organ systems, such as microbial metabolites, enteroendocrine peptides, bile acids, and cytokines.In this review, we highlight 4 recent and impactful studies published in Cellular and Molecular Gastroenterology and Hepatology that exemplify these advances. Each study offers a unique window into the mechanisms by which gut-derived signals influence host metabolism and disease states. Together, they deepen the understanding of the complex dialogue between organs and open new avenues for therapeutic exploration. We conclude by discussing the implications of these findings and outlining emerging questions and future directions for the field.http://www.sciencedirect.com/science/article/pii/S2352345X25000712Gut MicrobiomeInterorgan CommunicationMetabolic DiseaseMicrobial MetabolitesGut-Liver AxisSystems Biology
spellingShingle Tien S. Dong
Emeran Mayer
Interorgan and Transcellular Communication in Metabolic Disease: Insights From Recent CMGH Studies
Cellular and Molecular Gastroenterology and Hepatology
Gut Microbiome
Interorgan Communication
Metabolic Disease
Microbial Metabolites
Gut-Liver Axis
Systems Biology
title Interorgan and Transcellular Communication in Metabolic Disease: Insights From Recent CMGH Studies
title_full Interorgan and Transcellular Communication in Metabolic Disease: Insights From Recent CMGH Studies
title_fullStr Interorgan and Transcellular Communication in Metabolic Disease: Insights From Recent CMGH Studies
title_full_unstemmed Interorgan and Transcellular Communication in Metabolic Disease: Insights From Recent CMGH Studies
title_short Interorgan and Transcellular Communication in Metabolic Disease: Insights From Recent CMGH Studies
title_sort interorgan and transcellular communication in metabolic disease insights from recent cmgh studies
topic Gut Microbiome
Interorgan Communication
Metabolic Disease
Microbial Metabolites
Gut-Liver Axis
Systems Biology
url http://www.sciencedirect.com/science/article/pii/S2352345X25000712
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