Chronic stress in mice: how gut bacteria influence gene activity in key brain neurons
Abstract Major depressive disorder (MDD) is a serious mental disorder. Increasing evidence suggests that changes of gut microbiota are involved in pathogenesis of depression, yet the underlying mechanisms remains unknown. Here, chronic unpredictable mild stress (CUMS) mice model was constructed to m...
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Nature Publishing Group
2025-08-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-025-03479-0 |
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| author | Wenxia Jiang Yifan Li Jie Yang Xunmin Tan Ruimin Tian Guojing Ma Jing Wu Jianping Zhang Yu Huang Ping Liu Minghao Yuan Xiaodong Song Leyao Luo Xingyu Zhou Hongzhou Zuo Ma-Li Wong Julio Licino Peng Zheng |
| author_facet | Wenxia Jiang Yifan Li Jie Yang Xunmin Tan Ruimin Tian Guojing Ma Jing Wu Jianping Zhang Yu Huang Ping Liu Minghao Yuan Xiaodong Song Leyao Luo Xingyu Zhou Hongzhou Zuo Ma-Li Wong Julio Licino Peng Zheng |
| author_sort | Wenxia Jiang |
| collection | DOAJ |
| description | Abstract Major depressive disorder (MDD) is a serious mental disorder. Increasing evidence suggests that changes of gut microbiota are involved in pathogenesis of depression, yet the underlying mechanisms remains unknown. Here, chronic unpredictable mild stress (CUMS) mice model was constructed to mimic depression. We characterized the microbial composition and function of control, bedding exchange, and CUMS mice through 16S rRNA gene and metagenomic sequencing. Additionally, single-nucleus RNA sequencing (snRNA-seq) was used to compare the transcriptomic changes in the hypothalamus of these three groups. We found that replacing the bedding of CUMS mice with that of control mice could reverse the depressive-like behaviors. The microbial signatures of bedding exchange group trended towards the control group at the genus level. The abundance of g_norank_f_Muribaculaceae significantly increased in the bedding exchange group compared to CUMS group. Meanwhile, we found that the CUMS mice were characterized by cell-specific transcriptomic changes in hypothalamus. Notably, the transcriptomes of excitatory neurons in the hypothalamus were mainly affected, and these changes could be effectively reversed by bedding exchange treatment. The gene modules analysis revealed that the gut microbiota mainly modulated glyoxylate and dicarboxylate metabolism as well as arginine biosynthesis in hypothalamic excitatory neurons. Our findings provide new insights into the pathogenesis of depression. |
| format | Article |
| id | doaj-art-9859fd5619d64e52a4eecaf52e64bc93 |
| institution | Kabale University |
| issn | 2158-3188 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj-art-9859fd5619d64e52a4eecaf52e64bc932025-08-20T03:42:07ZengNature Publishing GroupTranslational Psychiatry2158-31882025-08-0115111410.1038/s41398-025-03479-0Chronic stress in mice: how gut bacteria influence gene activity in key brain neuronsWenxia Jiang0Yifan Li1Jie Yang2Xunmin Tan3Ruimin Tian4Guojing Ma5Jing Wu6Jianping Zhang7Yu Huang8Ping Liu9Minghao Yuan10Xiaodong Song11Leyao Luo12Xingyu Zhou13Hongzhou Zuo14Ma-Li Wong15Julio Licino16Peng Zheng17Department of Neurology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Psychiatry, College of Medicine, SUNY Upstate Medical UniversityDepartment of Psychiatry, Cornell UniversityDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical UniversityAbstract Major depressive disorder (MDD) is a serious mental disorder. Increasing evidence suggests that changes of gut microbiota are involved in pathogenesis of depression, yet the underlying mechanisms remains unknown. Here, chronic unpredictable mild stress (CUMS) mice model was constructed to mimic depression. We characterized the microbial composition and function of control, bedding exchange, and CUMS mice through 16S rRNA gene and metagenomic sequencing. Additionally, single-nucleus RNA sequencing (snRNA-seq) was used to compare the transcriptomic changes in the hypothalamus of these three groups. We found that replacing the bedding of CUMS mice with that of control mice could reverse the depressive-like behaviors. The microbial signatures of bedding exchange group trended towards the control group at the genus level. The abundance of g_norank_f_Muribaculaceae significantly increased in the bedding exchange group compared to CUMS group. Meanwhile, we found that the CUMS mice were characterized by cell-specific transcriptomic changes in hypothalamus. Notably, the transcriptomes of excitatory neurons in the hypothalamus were mainly affected, and these changes could be effectively reversed by bedding exchange treatment. The gene modules analysis revealed that the gut microbiota mainly modulated glyoxylate and dicarboxylate metabolism as well as arginine biosynthesis in hypothalamic excitatory neurons. Our findings provide new insights into the pathogenesis of depression.https://doi.org/10.1038/s41398-025-03479-0 |
| spellingShingle | Wenxia Jiang Yifan Li Jie Yang Xunmin Tan Ruimin Tian Guojing Ma Jing Wu Jianping Zhang Yu Huang Ping Liu Minghao Yuan Xiaodong Song Leyao Luo Xingyu Zhou Hongzhou Zuo Ma-Li Wong Julio Licino Peng Zheng Chronic stress in mice: how gut bacteria influence gene activity in key brain neurons Translational Psychiatry |
| title | Chronic stress in mice: how gut bacteria influence gene activity in key brain neurons |
| title_full | Chronic stress in mice: how gut bacteria influence gene activity in key brain neurons |
| title_fullStr | Chronic stress in mice: how gut bacteria influence gene activity in key brain neurons |
| title_full_unstemmed | Chronic stress in mice: how gut bacteria influence gene activity in key brain neurons |
| title_short | Chronic stress in mice: how gut bacteria influence gene activity in key brain neurons |
| title_sort | chronic stress in mice how gut bacteria influence gene activity in key brain neurons |
| url | https://doi.org/10.1038/s41398-025-03479-0 |
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