Gut microbiota dysbiosis promotes cognitive impairment via bile acid metabolism in major depressive disorder

Abstract Evidence suggests that complex interactions among the gut microbiome, metabolic abnormalities, and brain have important etiological and therapeutic implications in major depressive disorder (MDD). However, the influence of microbiome-gut-brain cross-talk on cognitive impairment in MDD remai...

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Main Authors: Min Jia, Yajuan Fan, Qingyan Ma, Ding Yang, Yunpeng Wang, Xiaoyan He, Binbin Zhao, Xianyan Zhan, Zhiyang Qi, Yifan Ren, Ziqing Dong, Feng Zhu, Wei Wang, Yuan Gao, Xiancang Ma
Format: Article
Language:English
Published: Nature Publishing Group 2024-12-01
Series:Translational Psychiatry
Online Access:https://doi.org/10.1038/s41398-024-03211-4
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author Min Jia
Yajuan Fan
Qingyan Ma
Ding Yang
Yunpeng Wang
Xiaoyan He
Binbin Zhao
Xianyan Zhan
Zhiyang Qi
Yifan Ren
Ziqing Dong
Feng Zhu
Wei Wang
Yuan Gao
Xiancang Ma
author_facet Min Jia
Yajuan Fan
Qingyan Ma
Ding Yang
Yunpeng Wang
Xiaoyan He
Binbin Zhao
Xianyan Zhan
Zhiyang Qi
Yifan Ren
Ziqing Dong
Feng Zhu
Wei Wang
Yuan Gao
Xiancang Ma
author_sort Min Jia
collection DOAJ
description Abstract Evidence suggests that complex interactions among the gut microbiome, metabolic abnormalities, and brain have important etiological and therapeutic implications in major depressive disorder (MDD). However, the influence of microbiome-gut-brain cross-talk on cognitive impairment in MDD remains poorly characterized. We performed serum metabolomic profiling on 104 patients with MDD and 77 healthy controls (HCs), and also performed fecal metagenomic sequencing on a subset of these individuals, including 79 MDD patients and 60 HCs. The findings were validated in a separate cohort that included 40 patients with MDD and 40 HCs using serum-targeted metabolomics. Abnormal bile acid metabolism was observed in patients with MDD, which is related to cognitive dysfunction. The following gut microbiota corresponded to changes in bile acid metabolism and enzyme activities involved in the bile acid metabolic pathway, including Lachnospiraceae (Blautia_massiliensis, Anaerostipes_hadrus, Dorea_formicigenerans, and Fusicatenibacter_saccharivorans), Ruminococcaceae (Ruminococcus_bromii, Flavonifractor_plautii, and Ruthenibacterium_lactatiformans), and Escherichia_coli. Furthermore, a combinatorial marker classifier that robustly differentiated patients with MDD from HCs was identified. In conclusion, this study provides insights into the gut-brain interactions in the cognitive phenotype of MDD, indicating a potential therapeutic strategy for MDD-associated cognitive impairment by targeting the gut microbiota and bile acid metabolism.
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spelling doaj-art-a3e653a96aa44d3691f5b25029f189b22025-08-20T02:43:35ZengNature Publishing GroupTranslational Psychiatry2158-31882024-12-0114111510.1038/s41398-024-03211-4Gut microbiota dysbiosis promotes cognitive impairment via bile acid metabolism in major depressive disorderMin Jia0Yajuan Fan1Qingyan Ma2Ding Yang3Yunpeng Wang4Xiaoyan He5Binbin Zhao6Xianyan Zhan7Zhiyang Qi8Yifan Ren9Ziqing Dong10Feng Zhu11Wei Wang12Yuan Gao13Xiancang Ma14Department of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong UniversityShaanxi Belt and Road Joint Laboratory of Precision Medicine in Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong UniversityAbstract Evidence suggests that complex interactions among the gut microbiome, metabolic abnormalities, and brain have important etiological and therapeutic implications in major depressive disorder (MDD). However, the influence of microbiome-gut-brain cross-talk on cognitive impairment in MDD remains poorly characterized. We performed serum metabolomic profiling on 104 patients with MDD and 77 healthy controls (HCs), and also performed fecal metagenomic sequencing on a subset of these individuals, including 79 MDD patients and 60 HCs. The findings were validated in a separate cohort that included 40 patients with MDD and 40 HCs using serum-targeted metabolomics. Abnormal bile acid metabolism was observed in patients with MDD, which is related to cognitive dysfunction. The following gut microbiota corresponded to changes in bile acid metabolism and enzyme activities involved in the bile acid metabolic pathway, including Lachnospiraceae (Blautia_massiliensis, Anaerostipes_hadrus, Dorea_formicigenerans, and Fusicatenibacter_saccharivorans), Ruminococcaceae (Ruminococcus_bromii, Flavonifractor_plautii, and Ruthenibacterium_lactatiformans), and Escherichia_coli. Furthermore, a combinatorial marker classifier that robustly differentiated patients with MDD from HCs was identified. In conclusion, this study provides insights into the gut-brain interactions in the cognitive phenotype of MDD, indicating a potential therapeutic strategy for MDD-associated cognitive impairment by targeting the gut microbiota and bile acid metabolism.https://doi.org/10.1038/s41398-024-03211-4
spellingShingle Min Jia
Yajuan Fan
Qingyan Ma
Ding Yang
Yunpeng Wang
Xiaoyan He
Binbin Zhao
Xianyan Zhan
Zhiyang Qi
Yifan Ren
Ziqing Dong
Feng Zhu
Wei Wang
Yuan Gao
Xiancang Ma
Gut microbiota dysbiosis promotes cognitive impairment via bile acid metabolism in major depressive disorder
Translational Psychiatry
title Gut microbiota dysbiosis promotes cognitive impairment via bile acid metabolism in major depressive disorder
title_full Gut microbiota dysbiosis promotes cognitive impairment via bile acid metabolism in major depressive disorder
title_fullStr Gut microbiota dysbiosis promotes cognitive impairment via bile acid metabolism in major depressive disorder
title_full_unstemmed Gut microbiota dysbiosis promotes cognitive impairment via bile acid metabolism in major depressive disorder
title_short Gut microbiota dysbiosis promotes cognitive impairment via bile acid metabolism in major depressive disorder
title_sort gut microbiota dysbiosis promotes cognitive impairment via bile acid metabolism in major depressive disorder
url https://doi.org/10.1038/s41398-024-03211-4
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