Proteomics analysis of the gut–brain axis in a gut microbiota-dysbiosis model of depression

Abstract Major depressive disorder (MDD) is a serious mental illness. Increasing evidence from both animal and human studies suggested that the gut microbiota might be involved in the onset of depression via the gut–brain axis. However, the mechanism in depression remains unclear. To explore the pro...

Full description

Bibliographic Details
Main Authors: Yiyun Liu, Haiyang Wang, Siwen Gui, Benhua Zeng, Juncai Pu, Peng Zheng, Li Zeng, Yuanyuan Luo, You Wu, Chanjuan Zhou, Jinlin Song, Ping Ji, Hong Wei, Peng Xie
Format: Article
Language:English
Published: Nature Publishing Group 2021-11-01
Series:Translational Psychiatry
Online Access:https://doi.org/10.1038/s41398-021-01689-w
_version_ 1818394444409339904
author Yiyun Liu
Haiyang Wang
Siwen Gui
Benhua Zeng
Juncai Pu
Peng Zheng
Li Zeng
Yuanyuan Luo
You Wu
Chanjuan Zhou
Jinlin Song
Ping Ji
Hong Wei
Peng Xie
author_facet Yiyun Liu
Haiyang Wang
Siwen Gui
Benhua Zeng
Juncai Pu
Peng Zheng
Li Zeng
Yuanyuan Luo
You Wu
Chanjuan Zhou
Jinlin Song
Ping Ji
Hong Wei
Peng Xie
author_sort Yiyun Liu
collection DOAJ
description Abstract Major depressive disorder (MDD) is a serious mental illness. Increasing evidence from both animal and human studies suggested that the gut microbiota might be involved in the onset of depression via the gut–brain axis. However, the mechanism in depression remains unclear. To explore the protein changes of the gut–brain axis modulated by gut microbiota, germ-free mice were transplanted with gut microbiota from MDD patients to induce depression-like behaviors. Behavioral tests were performed following fecal microbiota transplantation. A quantitative proteomics approach was used to examine changes in protein expression in the prefrontal cortex (PFC), liver, cecum, and serum. Then differential protein analysis and weighted gene coexpression network analysis were used to identify microbiota-related protein modules. Our results suggested that gut microbiota induced the alteration of protein expression levels in multiple tissues of the gut–brain axis in mice with depression-like phenotype, and these changes of the PFC and liver were model specific compared to chronic stress models. Gene ontology enrichment analysis revealed that the protein changes of the gut–brain axis were involved in a variety of biological functions, including metabolic process and inflammatory response, in which energy metabolism is the core change of the protein network. Our data provide clues for future studies in the gut–brain axis on protein level and deepen the understanding of how gut microbiota cause depression-like behaviors.
first_indexed 2024-12-14T06:01:18Z
format Article
id doaj.art-82d254e278474f6899126156665a0729
institution Directory Open Access Journal
issn 2158-3188
language English
last_indexed 2024-12-14T06:01:18Z
publishDate 2021-11-01
publisher Nature Publishing Group
record_format Article
series Translational Psychiatry
spelling doaj.art-82d254e278474f6899126156665a07292022-12-21T23:14:25ZengNature Publishing GroupTranslational Psychiatry2158-31882021-11-011111810.1038/s41398-021-01689-wProteomics analysis of the gut–brain axis in a gut microbiota-dysbiosis model of depressionYiyun Liu0Haiyang Wang1Siwen Gui2Benhua Zeng3Juncai Pu4Peng Zheng5Li Zeng6Yuanyuan Luo7You Wu8Chanjuan Zhou9Jinlin Song10Ping Ji11Hong Wei12Peng Xie13NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical UniversityNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical UniversityNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical UniversityNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical UniversityNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical UniversityNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical UniversityNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical UniversityNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical UniversityNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical UniversityCollege of Stomatology, Chongqing Medical UniversityCollege of Stomatology, Chongqing Medical UniversityDepartment of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical UniversityNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical UniversityAbstract Major depressive disorder (MDD) is a serious mental illness. Increasing evidence from both animal and human studies suggested that the gut microbiota might be involved in the onset of depression via the gut–brain axis. However, the mechanism in depression remains unclear. To explore the protein changes of the gut–brain axis modulated by gut microbiota, germ-free mice were transplanted with gut microbiota from MDD patients to induce depression-like behaviors. Behavioral tests were performed following fecal microbiota transplantation. A quantitative proteomics approach was used to examine changes in protein expression in the prefrontal cortex (PFC), liver, cecum, and serum. Then differential protein analysis and weighted gene coexpression network analysis were used to identify microbiota-related protein modules. Our results suggested that gut microbiota induced the alteration of protein expression levels in multiple tissues of the gut–brain axis in mice with depression-like phenotype, and these changes of the PFC and liver were model specific compared to chronic stress models. Gene ontology enrichment analysis revealed that the protein changes of the gut–brain axis were involved in a variety of biological functions, including metabolic process and inflammatory response, in which energy metabolism is the core change of the protein network. Our data provide clues for future studies in the gut–brain axis on protein level and deepen the understanding of how gut microbiota cause depression-like behaviors.https://doi.org/10.1038/s41398-021-01689-w
spellingShingle Yiyun Liu
Haiyang Wang
Siwen Gui
Benhua Zeng
Juncai Pu
Peng Zheng
Li Zeng
Yuanyuan Luo
You Wu
Chanjuan Zhou
Jinlin Song
Ping Ji
Hong Wei
Peng Xie
Proteomics analysis of the gut–brain axis in a gut microbiota-dysbiosis model of depression
Translational Psychiatry
title Proteomics analysis of the gut–brain axis in a gut microbiota-dysbiosis model of depression
title_full Proteomics analysis of the gut–brain axis in a gut microbiota-dysbiosis model of depression
title_fullStr Proteomics analysis of the gut–brain axis in a gut microbiota-dysbiosis model of depression
title_full_unstemmed Proteomics analysis of the gut–brain axis in a gut microbiota-dysbiosis model of depression
title_short Proteomics analysis of the gut–brain axis in a gut microbiota-dysbiosis model of depression
title_sort proteomics analysis of the gut brain axis in a gut microbiota dysbiosis model of depression
url https://doi.org/10.1038/s41398-021-01689-w
work_keys_str_mv AT yiyunliu proteomicsanalysisofthegutbrainaxisinagutmicrobiotadysbiosismodelofdepression
AT haiyangwang proteomicsanalysisofthegutbrainaxisinagutmicrobiotadysbiosismodelofdepression
AT siwengui proteomicsanalysisofthegutbrainaxisinagutmicrobiotadysbiosismodelofdepression
AT benhuazeng proteomicsanalysisofthegutbrainaxisinagutmicrobiotadysbiosismodelofdepression
AT juncaipu proteomicsanalysisofthegutbrainaxisinagutmicrobiotadysbiosismodelofdepression
AT pengzheng proteomicsanalysisofthegutbrainaxisinagutmicrobiotadysbiosismodelofdepression
AT lizeng proteomicsanalysisofthegutbrainaxisinagutmicrobiotadysbiosismodelofdepression
AT yuanyuanluo proteomicsanalysisofthegutbrainaxisinagutmicrobiotadysbiosismodelofdepression
AT youwu proteomicsanalysisofthegutbrainaxisinagutmicrobiotadysbiosismodelofdepression
AT chanjuanzhou proteomicsanalysisofthegutbrainaxisinagutmicrobiotadysbiosismodelofdepression
AT jinlinsong proteomicsanalysisofthegutbrainaxisinagutmicrobiotadysbiosismodelofdepression
AT pingji proteomicsanalysisofthegutbrainaxisinagutmicrobiotadysbiosismodelofdepression
AT hongwei proteomicsanalysisofthegutbrainaxisinagutmicrobiotadysbiosismodelofdepression
AT pengxie proteomicsanalysisofthegutbrainaxisinagutmicrobiotadysbiosismodelofdepression