Perturbations in the microbiota-gut-brain axis shaped by social status loss
Abstract Social status is closely linked to physiological and psychological states. Loss of social dominance can lead to brain disorders such as depression, but the underlying mechanisms remain unclear. The gut microbiota can sense stress and contribute to brain disorders via the microbiota-gut-brai...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-03-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07850-1 |
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| author | Ruijing Yang Xin Wang Jie Yang Xingyu Zhou Yiyuan Wu Yifan Li Yu Huang Jianping Zhang Ping Liu Minghao Yuan Xunmin Tan Peng Zheng Jing Wu |
| author_facet | Ruijing Yang Xin Wang Jie Yang Xingyu Zhou Yiyuan Wu Yifan Li Yu Huang Jianping Zhang Ping Liu Minghao Yuan Xunmin Tan Peng Zheng Jing Wu |
| author_sort | Ruijing Yang |
| collection | DOAJ |
| description | Abstract Social status is closely linked to physiological and psychological states. Loss of social dominance can lead to brain disorders such as depression, but the underlying mechanisms remain unclear. The gut microbiota can sense stress and contribute to brain disorders via the microbiota-gut-brain axis (MGBA). Here, using a forced loss paradigm to demote dominant mice to subordinate ranks, we find that stress alters the composition and function of the gut microbiota, increasing Muribaculaceae abundance and enhancing butanoate metabolism, and gut microbial depletion resists forced loss-induced hierarchical demotion and behavioral alteration. Single-nucleus transcriptomic analysis of the prefrontal cortex (PFC) indicates that social status loss primarily affected interneurons, altering GABAergic synaptic transmission. Weighted gene co-expression network analysis (WGCNA) reveals modules linked to forced loss in the gut microbiota, colon, PFC, and PFC interneurons, suggesting changes in the PI3K-Akt signaling pathway and the glutamatergic synapse. Our findings provide evidence for MGBA perturbations induced by social status loss, offering potential intervention targets for related brain disorders. |
| format | Article |
| id | doaj-art-eccffb0dce174d8f953cb070417bfa7d |
| institution | OA Journals |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-eccffb0dce174d8f953cb070417bfa7d2025-08-20T01:57:45ZengNature PortfolioCommunications Biology2399-36422025-03-018111510.1038/s42003-025-07850-1Perturbations in the microbiota-gut-brain axis shaped by social status lossRuijing Yang0Xin Wang1Jie Yang2Xingyu Zhou3Yiyuan Wu4Yifan Li5Yu Huang6Jianping Zhang7Ping Liu8Minghao Yuan9Xunmin Tan10Peng Zheng11Jing Wu12Department 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 UniversityAbstract Social status is closely linked to physiological and psychological states. Loss of social dominance can lead to brain disorders such as depression, but the underlying mechanisms remain unclear. The gut microbiota can sense stress and contribute to brain disorders via the microbiota-gut-brain axis (MGBA). Here, using a forced loss paradigm to demote dominant mice to subordinate ranks, we find that stress alters the composition and function of the gut microbiota, increasing Muribaculaceae abundance and enhancing butanoate metabolism, and gut microbial depletion resists forced loss-induced hierarchical demotion and behavioral alteration. Single-nucleus transcriptomic analysis of the prefrontal cortex (PFC) indicates that social status loss primarily affected interneurons, altering GABAergic synaptic transmission. Weighted gene co-expression network analysis (WGCNA) reveals modules linked to forced loss in the gut microbiota, colon, PFC, and PFC interneurons, suggesting changes in the PI3K-Akt signaling pathway and the glutamatergic synapse. Our findings provide evidence for MGBA perturbations induced by social status loss, offering potential intervention targets for related brain disorders.https://doi.org/10.1038/s42003-025-07850-1 |
| spellingShingle | Ruijing Yang Xin Wang Jie Yang Xingyu Zhou Yiyuan Wu Yifan Li Yu Huang Jianping Zhang Ping Liu Minghao Yuan Xunmin Tan Peng Zheng Jing Wu Perturbations in the microbiota-gut-brain axis shaped by social status loss Communications Biology |
| title | Perturbations in the microbiota-gut-brain axis shaped by social status loss |
| title_full | Perturbations in the microbiota-gut-brain axis shaped by social status loss |
| title_fullStr | Perturbations in the microbiota-gut-brain axis shaped by social status loss |
| title_full_unstemmed | Perturbations in the microbiota-gut-brain axis shaped by social status loss |
| title_short | Perturbations in the microbiota-gut-brain axis shaped by social status loss |
| title_sort | perturbations in the microbiota gut brain axis shaped by social status loss |
| url | https://doi.org/10.1038/s42003-025-07850-1 |
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