{"title":"Sympathetic Overactivation Drives Colonic Eosinophil Infiltration Linked to Visceral Hypersensitivity in Irritable Bowel Syndrome.","authors":"Shaoqi Duan, Hirosato Kanda, Feng Zhu, Masamichi Okubo, Taro Koike, Yoshiya Ohno, Toshiyuki Tanaka, Yukiko Harima, Kazunari Miyamichi, Hirokazu Fukui, Shinichiro Shinzaki, Yilong Cui, Koichi Noguchi, Yi Dai","doi":"10.1016/j.jcmgh.2025.101658","DOIUrl":null,"url":null,"abstract":"<p><strong>Background & aims: </strong>Mucosal immune alteration is a characteristic clinical manifestation of irritable bowel syndrome (IBS), and its symptoms are often triggered by psychological stress. The present study aimed to investigate the impact of early life stress-associated dysfunction of the sympathetic nervous system (SNS) on mucosal immune changes in the gastrointestinal tract (GI) and its contribution to visceral hypersensitivity of IBS.</p><p><strong>Methods: </strong>We utilized a traditional animal model of IBS with maternal separation (MS) and evaluated colorectal hypersensitivity, immune alteration, and SNS activity in adult rats with MS. We conducted a series of experiments to manipulate peripheral SNS activity pharmacologically and chemogenetically to explore the interaction between SNS activity and GI events.</p><p><strong>Results: </strong>The MS-induced IBS model exhibited visceral hypersensitivity and eosinophilic infiltration in the colonic mucosa, along with SNS overactivation. Degeneration of the SNS using 6-OHDA neurotoxin decreased eosinophil infiltration and visceral hypersensitivity in the MS model. Notably, specific chemogenetic activation of the peripheral SNS induced eosinophil infiltration in the intestinal mucosa through the noradrenergic signalling-mediated release of eotaxin-1 from mesenchymal cells.</p><p><strong>Conclusion: </strong>This study highlights the critical role of SNS overactivation in eotaxin-1-driven eosinophil infiltration in the colon, leading to the development of visceral hypersensitivity in IBS. The results provide important insights into the mechanistic links among increased sympathetic activity, mucosal immune alteration, and visceral hypersensitivity in individuals with IBS, suggesting potential therapeutic approaches.</p>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":" ","pages":"101658"},"PeriodicalIF":7.1000,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cellular and Molecular Gastroenterology and Hepatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jcmgh.2025.101658","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background & aims: Mucosal immune alteration is a characteristic clinical manifestation of irritable bowel syndrome (IBS), and its symptoms are often triggered by psychological stress. The present study aimed to investigate the impact of early life stress-associated dysfunction of the sympathetic nervous system (SNS) on mucosal immune changes in the gastrointestinal tract (GI) and its contribution to visceral hypersensitivity of IBS.
Methods: We utilized a traditional animal model of IBS with maternal separation (MS) and evaluated colorectal hypersensitivity, immune alteration, and SNS activity in adult rats with MS. We conducted a series of experiments to manipulate peripheral SNS activity pharmacologically and chemogenetically to explore the interaction between SNS activity and GI events.
Results: The MS-induced IBS model exhibited visceral hypersensitivity and eosinophilic infiltration in the colonic mucosa, along with SNS overactivation. Degeneration of the SNS using 6-OHDA neurotoxin decreased eosinophil infiltration and visceral hypersensitivity in the MS model. Notably, specific chemogenetic activation of the peripheral SNS induced eosinophil infiltration in the intestinal mucosa through the noradrenergic signalling-mediated release of eotaxin-1 from mesenchymal cells.
Conclusion: This study highlights the critical role of SNS overactivation in eotaxin-1-driven eosinophil infiltration in the colon, leading to the development of visceral hypersensitivity in IBS. The results provide important insights into the mechanistic links among increased sympathetic activity, mucosal immune alteration, and visceral hypersensitivity in individuals with IBS, suggesting potential therapeutic approaches.
期刊介绍：
"Cell and Molecular Gastroenterology and Hepatology (CMGH)" is a journal dedicated to advancing the understanding of digestive biology through impactful research that spans the spectrum of normal gastrointestinal, hepatic, and pancreatic functions, as well as their pathologies. The journal's mission is to publish high-quality, hypothesis-driven studies that offer mechanistic novelty and are methodologically robust, covering a wide range of themes in gastroenterology, hepatology, and pancreatology.
CMGH reports on the latest scientific advances in cell biology, immunology, physiology, microbiology, genetics, and neurobiology related to gastrointestinal, hepatobiliary, and pancreatic health and disease. The research published in CMGH is designed to address significant questions in the field, utilizing a variety of experimental approaches, including in vitro models, patient-derived tissues or cells, and animal models. This multifaceted approach enables the journal to contribute to both fundamental discoveries and their translation into clinical applications, ultimately aiming to improve patient care and treatment outcomes in digestive health.
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