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Integrated phosphoproteomic and metabolomic profiling reveals perturbed pathways in the hippocampus of gut microbiota dysbiosis mice
The dysbiosis of gut microbiota is an important environmental factor that can induce mental disorders, such as depression, through the microbiota–gut–brain axis. However, the underlying pathogenic mechanisms are complex and not completely understood. Here we utilized mass spectrometry to identify th...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553953/ https://www.ncbi.nlm.nih.gov/pubmed/33051451 http://dx.doi.org/10.1038/s41398-020-01024-9 |
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author | Wang, Haiyang Liu, Lanxiang Rao, Xuechen Zeng, Benhua Yu, Ying Zhou, Chanjuan Zeng, Li Zheng, Peng Pu, Juncai Xu, Shaohua Cheng, Ke Zhang, Hanping Ji, Ping Wei, Hong Xie, Peng |
author_facet | Wang, Haiyang Liu, Lanxiang Rao, Xuechen Zeng, Benhua Yu, Ying Zhou, Chanjuan Zeng, Li Zheng, Peng Pu, Juncai Xu, Shaohua Cheng, Ke Zhang, Hanping Ji, Ping Wei, Hong Xie, Peng |
author_sort | Wang, Haiyang |
collection | PubMed |
description | The dysbiosis of gut microbiota is an important environmental factor that can induce mental disorders, such as depression, through the microbiota–gut–brain axis. However, the underlying pathogenic mechanisms are complex and not completely understood. Here we utilized mass spectrometry to identify the global phosphorylation dynamics in hippocampus tissue in germ-free mice and specific pathogen-free mice (GF vs SPF), fecal microbiota transplantation (FMT) model (“depression microbiota” and the “healthy microbiota” recipient mice). As a result, 327 phosphosites of 237 proteins in GF vs SPF, and 478 phosphosites of 334 proteins in “depression microbiota” vs “healthy microbiota” recipient mice were identified as significant. These phosphorylation dysregulations were consistently associated with glutamatergic neurotransmitter system disturbances. The FMT mice exhibited disturbances in lipid metabolism and amino acid metabolism in both the periphery and brain through integrating phosphoproteomic and metabolomic analysis. Moreover, CAMKII-CREB signaling pathway, in response to these disturbances, was the primary common perturbed cellular process. In addition, we demonstrated that the spliceosome, never directly implicated in mental disorders previously, was a substantially neuronal function disrupted by gut microbiota dysbiosis, and the NCBP1 phosphorylation was identified as a novel pathogenic target. These results present a new perspective to study the pathologic mechanisms of gut microbiota dysbiosis related depression and highlight potential gut-mediated therapies for depression. |
format | Online Article Text |
id | pubmed-7553953 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-75539532020-10-19 Integrated phosphoproteomic and metabolomic profiling reveals perturbed pathways in the hippocampus of gut microbiota dysbiosis mice Wang, Haiyang Liu, Lanxiang Rao, Xuechen Zeng, Benhua Yu, Ying Zhou, Chanjuan Zeng, Li Zheng, Peng Pu, Juncai Xu, Shaohua Cheng, Ke Zhang, Hanping Ji, Ping Wei, Hong Xie, Peng Transl Psychiatry Article The dysbiosis of gut microbiota is an important environmental factor that can induce mental disorders, such as depression, through the microbiota–gut–brain axis. However, the underlying pathogenic mechanisms are complex and not completely understood. Here we utilized mass spectrometry to identify the global phosphorylation dynamics in hippocampus tissue in germ-free mice and specific pathogen-free mice (GF vs SPF), fecal microbiota transplantation (FMT) model (“depression microbiota” and the “healthy microbiota” recipient mice). As a result, 327 phosphosites of 237 proteins in GF vs SPF, and 478 phosphosites of 334 proteins in “depression microbiota” vs “healthy microbiota” recipient mice were identified as significant. These phosphorylation dysregulations were consistently associated with glutamatergic neurotransmitter system disturbances. The FMT mice exhibited disturbances in lipid metabolism and amino acid metabolism in both the periphery and brain through integrating phosphoproteomic and metabolomic analysis. Moreover, CAMKII-CREB signaling pathway, in response to these disturbances, was the primary common perturbed cellular process. In addition, we demonstrated that the spliceosome, never directly implicated in mental disorders previously, was a substantially neuronal function disrupted by gut microbiota dysbiosis, and the NCBP1 phosphorylation was identified as a novel pathogenic target. These results present a new perspective to study the pathologic mechanisms of gut microbiota dysbiosis related depression and highlight potential gut-mediated therapies for depression. Nature Publishing Group UK 2020-10-13 /pmc/articles/PMC7553953/ /pubmed/33051451 http://dx.doi.org/10.1038/s41398-020-01024-9 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Wang, Haiyang Liu, Lanxiang Rao, Xuechen Zeng, Benhua Yu, Ying Zhou, Chanjuan Zeng, Li Zheng, Peng Pu, Juncai Xu, Shaohua Cheng, Ke Zhang, Hanping Ji, Ping Wei, Hong Xie, Peng Integrated phosphoproteomic and metabolomic profiling reveals perturbed pathways in the hippocampus of gut microbiota dysbiosis mice |
title | Integrated phosphoproteomic and metabolomic profiling reveals perturbed pathways in the hippocampus of gut microbiota dysbiosis mice |
title_full | Integrated phosphoproteomic and metabolomic profiling reveals perturbed pathways in the hippocampus of gut microbiota dysbiosis mice |
title_fullStr | Integrated phosphoproteomic and metabolomic profiling reveals perturbed pathways in the hippocampus of gut microbiota dysbiosis mice |
title_full_unstemmed | Integrated phosphoproteomic and metabolomic profiling reveals perturbed pathways in the hippocampus of gut microbiota dysbiosis mice |
title_short | Integrated phosphoproteomic and metabolomic profiling reveals perturbed pathways in the hippocampus of gut microbiota dysbiosis mice |
title_sort | integrated phosphoproteomic and metabolomic profiling reveals perturbed pathways in the hippocampus of gut microbiota dysbiosis mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553953/ https://www.ncbi.nlm.nih.gov/pubmed/33051451 http://dx.doi.org/10.1038/s41398-020-01024-9 |
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