Circadian rhythm perturbation causes IBS-like characteristics and altered fecal metabolome in mice

Abstract Background Circadian rhythm disturbance is associated with functional gastrointestinal disorders such as irritable bowel syndrome (IBS). This study aimed to explore the effects of dysregulated circadian rhythm on visceral sensitivity, colonic permeability, gut microbial composition, and met...

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Main Authors: Gaichao Hong, Yajuan Zhao, Jieru Zhou, Lilin Hu, Gangping Li, Yu Jin
Format: Article
Language:English
Published: BMC 2025-05-01
Series:BMC Microbiology
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Online Access:https://doi.org/10.1186/s12866-025-04009-0
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author Gaichao Hong
Yajuan Zhao
Jieru Zhou
Lilin Hu
Gangping Li
Yu Jin
author_facet Gaichao Hong
Yajuan Zhao
Jieru Zhou
Lilin Hu
Gangping Li
Yu Jin
author_sort Gaichao Hong
collection DOAJ
description Abstract Background Circadian rhythm disturbance is associated with functional gastrointestinal disorders such as irritable bowel syndrome (IBS). This study aimed to explore the effects of dysregulated circadian rhythm on visceral sensitivity, colonic permeability, gut microbial composition, and metabolism in mice. Methods A murine model of circadian rhythm disturbance was built by performing a 6-hour phase delay. Visceral sensitivity was assessed using the abdominal withdrawal reflex score through colorectal distention. Colonic permeability was determined by measuring transepithelial resistance (TEER) and the permeability of fluorescent dextran 4 kDa. To gain insight into gut microbial composition and metabolism, 16S rRNA sequencing and untargeted metabolomics were conducted, respectively. Results Circadian rhythm disturbance led to IBS-like characteristics in mice, including visceral hypersensitivity and colonic hyperpermeability. Disrupted circadian rhythm also resulted in a decrease in intestinal microbial diversity and alterations in microbial structure. Several microbial genera were influenced by circadian rhythm disturbance, such as Bacteroides, Bifidobacterium, Desulfovibrio, Dubosiella, and Erysipelatoclostridium. Moreover, disrupted circadian rhythm altered metabolic profiles of gut microbiota and affected the levels of various metabolites, including 1-methylhistamine, nitrosylhaem, 3-aminocaproic acid, boviquinone, and carboplatin. Finally, circadian rhythm disturbance altered the relationship between microbial genera and metabolites. Conclusion Circadian rhythm disturbance contributes to visceral hypersensitivity and colonic hyperpermeability, while also altering the composition and metabolism of gut microbiota.
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spelling doaj-art-5c47cac5d73147d2b2b5f25f5d9cfc9f2025-08-20T03:53:11ZengBMCBMC Microbiology1471-21802025-05-0125111310.1186/s12866-025-04009-0Circadian rhythm perturbation causes IBS-like characteristics and altered fecal metabolome in miceGaichao Hong0Yajuan Zhao1Jieru Zhou2Lilin Hu3Gangping Li4Yu Jin5Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Gastroenterology, The Second Affiliated Hospital of Guangzhou Medical UniversityDivision of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDivision of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDivision of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDivision of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Background Circadian rhythm disturbance is associated with functional gastrointestinal disorders such as irritable bowel syndrome (IBS). This study aimed to explore the effects of dysregulated circadian rhythm on visceral sensitivity, colonic permeability, gut microbial composition, and metabolism in mice. Methods A murine model of circadian rhythm disturbance was built by performing a 6-hour phase delay. Visceral sensitivity was assessed using the abdominal withdrawal reflex score through colorectal distention. Colonic permeability was determined by measuring transepithelial resistance (TEER) and the permeability of fluorescent dextran 4 kDa. To gain insight into gut microbial composition and metabolism, 16S rRNA sequencing and untargeted metabolomics were conducted, respectively. Results Circadian rhythm disturbance led to IBS-like characteristics in mice, including visceral hypersensitivity and colonic hyperpermeability. Disrupted circadian rhythm also resulted in a decrease in intestinal microbial diversity and alterations in microbial structure. Several microbial genera were influenced by circadian rhythm disturbance, such as Bacteroides, Bifidobacterium, Desulfovibrio, Dubosiella, and Erysipelatoclostridium. Moreover, disrupted circadian rhythm altered metabolic profiles of gut microbiota and affected the levels of various metabolites, including 1-methylhistamine, nitrosylhaem, 3-aminocaproic acid, boviquinone, and carboplatin. Finally, circadian rhythm disturbance altered the relationship between microbial genera and metabolites. Conclusion Circadian rhythm disturbance contributes to visceral hypersensitivity and colonic hyperpermeability, while also altering the composition and metabolism of gut microbiota.https://doi.org/10.1186/s12866-025-04009-0Circadian rhythm disturbancePhase shiftIBSGut microbiotaMetabolism
spellingShingle Gaichao Hong
Yajuan Zhao
Jieru Zhou
Lilin Hu
Gangping Li
Yu Jin
Circadian rhythm perturbation causes IBS-like characteristics and altered fecal metabolome in mice
BMC Microbiology
Circadian rhythm disturbance
Phase shift
IBS
Gut microbiota
Metabolism
title Circadian rhythm perturbation causes IBS-like characteristics and altered fecal metabolome in mice
title_full Circadian rhythm perturbation causes IBS-like characteristics and altered fecal metabolome in mice
title_fullStr Circadian rhythm perturbation causes IBS-like characteristics and altered fecal metabolome in mice
title_full_unstemmed Circadian rhythm perturbation causes IBS-like characteristics and altered fecal metabolome in mice
title_short Circadian rhythm perturbation causes IBS-like characteristics and altered fecal metabolome in mice
title_sort circadian rhythm perturbation causes ibs like characteristics and altered fecal metabolome in mice
topic Circadian rhythm disturbance
Phase shift
IBS
Gut microbiota
Metabolism
url https://doi.org/10.1186/s12866-025-04009-0
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AT lilinhu circadianrhythmperturbationcausesibslikecharacteristicsandalteredfecalmetabolomeinmice
AT gangpingli circadianrhythmperturbationcausesibslikecharacteristicsandalteredfecalmetabolomeinmice
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