The gut–organ axis: Clinical aspects and immune mechanisms

The gut-brain axis exemplifies the bidirectional connection between the intestines and the brain, as evidenced by the impact of severe stress on gastrointestinal symptoms including abdominal pain and diarrhea, and conversely, the influence of abdominal discomfort on mood. Clinical observations suppo...

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Main Authors: Naoto Fukasawa, Junya Tsunoda, Shogo Sunaga, Hiroki Kiyohara, Nobuhiro Nakamoto, Toshiaki Teratani, Yohei Mikami, Takanori Kanai
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:Allergology International
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Online Access:http://www.sciencedirect.com/science/article/pii/S1323893025000097
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author Naoto Fukasawa
Junya Tsunoda
Shogo Sunaga
Hiroki Kiyohara
Nobuhiro Nakamoto
Toshiaki Teratani
Yohei Mikami
Takanori Kanai
author_facet Naoto Fukasawa
Junya Tsunoda
Shogo Sunaga
Hiroki Kiyohara
Nobuhiro Nakamoto
Toshiaki Teratani
Yohei Mikami
Takanori Kanai
author_sort Naoto Fukasawa
collection DOAJ
description The gut-brain axis exemplifies the bidirectional connection between the intestines and the brain, as evidenced by the impact of severe stress on gastrointestinal symptoms including abdominal pain and diarrhea, and conversely, the influence of abdominal discomfort on mood. Clinical observations support the notion of the gut–brain connection, including an increased prevalence of inflammatory bowel disease (IBD) in patients with depression and anxiety, as well as the association of changes in the gut microbiota with neurological disorders such as multiple sclerosis, Parkinson's disease, stroke and Alzheimer's disease. The gut and brain communicate via complex mechanisms involving inflammatory cytokines, immune cells, autonomic nerves, and gut microbiota, which contribute to the pathogenesis in certain gut and brain diseases. Two primary pathways mediate the bidirectional information exchange between the intestinal tract and the brain: signal transduction through bloodstream factors, such as bacterial metabolites and inflammatory cytokines, and neural pathways, such as neurotransmitters and inflammatory cytokines within the autonomic nervous system through the interaction between the nerve cells and beyond. In recent years, the basic mechanisms of the pathophysiology of the gut-brain axis have been gradually elucidated. Beyond the gut-brain interaction, emerging evidence suggests the influence of the gut extends to other organs, such as the liver and lungs, through intricate inter-organ communication pathways. An increasing number of reports on this clinical and basic cross-organ interactions underscore the potential for better understanding and novel therapeutic strategies targeting inter-organs networks. Further clarification of interactions between multiorgans premises transformative insights into cross-organ therapeutic strategies.
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spelling doaj-art-9ce0859f10d240d8bfe66ecce9f9d2f72025-08-20T03:42:19ZengElsevierAllergology International1323-89302025-04-0174219720910.1016/j.alit.2025.01.004The gut–organ axis: Clinical aspects and immune mechanismsNaoto Fukasawa0Junya Tsunoda1Shogo Sunaga2Hiroki Kiyohara3Nobuhiro Nakamoto4Toshiaki Teratani5Yohei Mikami6Takanori Kanai7Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, JapanDepartment of Surgery, Keio University School of Medicine, Tokyo, JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan; Corresponding author. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan; AMED-CREST, Japan Agency for Medical Research and Development, Tokyo, Japan; Corresponding author. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.The gut-brain axis exemplifies the bidirectional connection between the intestines and the brain, as evidenced by the impact of severe stress on gastrointestinal symptoms including abdominal pain and diarrhea, and conversely, the influence of abdominal discomfort on mood. Clinical observations support the notion of the gut–brain connection, including an increased prevalence of inflammatory bowel disease (IBD) in patients with depression and anxiety, as well as the association of changes in the gut microbiota with neurological disorders such as multiple sclerosis, Parkinson's disease, stroke and Alzheimer's disease. The gut and brain communicate via complex mechanisms involving inflammatory cytokines, immune cells, autonomic nerves, and gut microbiota, which contribute to the pathogenesis in certain gut and brain diseases. Two primary pathways mediate the bidirectional information exchange between the intestinal tract and the brain: signal transduction through bloodstream factors, such as bacterial metabolites and inflammatory cytokines, and neural pathways, such as neurotransmitters and inflammatory cytokines within the autonomic nervous system through the interaction between the nerve cells and beyond. In recent years, the basic mechanisms of the pathophysiology of the gut-brain axis have been gradually elucidated. Beyond the gut-brain interaction, emerging evidence suggests the influence of the gut extends to other organs, such as the liver and lungs, through intricate inter-organ communication pathways. An increasing number of reports on this clinical and basic cross-organ interactions underscore the potential for better understanding and novel therapeutic strategies targeting inter-organs networks. Further clarification of interactions between multiorgans premises transformative insights into cross-organ therapeutic strategies.http://www.sciencedirect.com/science/article/pii/S1323893025000097CytokinesGastrointestinal microbiomeGut-brain axisInflammatory bowel diseaseNeuroimmune interactions
spellingShingle Naoto Fukasawa
Junya Tsunoda
Shogo Sunaga
Hiroki Kiyohara
Nobuhiro Nakamoto
Toshiaki Teratani
Yohei Mikami
Takanori Kanai
The gut–organ axis: Clinical aspects and immune mechanisms
Allergology International
Cytokines
Gastrointestinal microbiome
Gut-brain axis
Inflammatory bowel disease
Neuroimmune interactions
title The gut–organ axis: Clinical aspects and immune mechanisms
title_full The gut–organ axis: Clinical aspects and immune mechanisms
title_fullStr The gut–organ axis: Clinical aspects and immune mechanisms
title_full_unstemmed The gut–organ axis: Clinical aspects and immune mechanisms
title_short The gut–organ axis: Clinical aspects and immune mechanisms
title_sort gut organ axis clinical aspects and immune mechanisms
topic Cytokines
Gastrointestinal microbiome
Gut-brain axis
Inflammatory bowel disease
Neuroimmune interactions
url http://www.sciencedirect.com/science/article/pii/S1323893025000097
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