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Gut bacteria-driven homovanillic acid alleviates depression by modulating synaptic integrity.
Zhao, Mingliang; Ren, Zhenxing; Zhao, Aihua; Tang, Yajun; Kuang, Junliang; Li, Mengci; Chen, Tianlu; Wang, Shouli; Wang, Jieyi; Zhang, Huiheng; Wang, Jijun; Zhang, Tianhong; Zeng, Jiahui; Liu, Xiaohua; Xie, Guoxiang; Liu, Penghong; Sun, Ning; Bao, Tianhao; Nie, Tongtong; Lin, Jingchao; Liu, Ping; Zheng, Yuanyi; Zheng, Xiaojiao; Liu, Tiemin; Jia, Wei.
Afiliação
  • Zhao M; Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
  • Ren Z; Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
  • Zhao A; Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
  • Tang Y; Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
  • Kuang J; Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
  • Li M; Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
  • Chen T; Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
  • Wang S; Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
  • Wang J; Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
  • Zhang H; Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
  • Wang J; Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai Intelligent Psychological Evaluation and Engineering Technology Research Center, Shanghai Key Laboratory of Psychotic Disorders, Shanghai 200030, China.
  • Zhang T; Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai Intelligent Psychological Evaluation and Engineering Technology Research Center, Shanghai Key Laboratory of Psychotic Disorders, Shanghai 200030, China.
  • Zeng J; Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai Intelligent Psychological Evaluation and Engineering Technology Research Center, Shanghai Key Laboratory of Psychotic Disorders, Shanghai 200030, China.
  • Liu X; Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai Intelligent Psychological Evaluation and Engineering Technology Research Center, Shanghai Key Laboratory of Psychotic Disorders, Shanghai 200030, China.
  • Xie G; Human Metabolomics Institute, Inc., Shenzhen 518109, China.
  • Liu P; Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan 030001, China.
  • Sun N; Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan 030001, China.
  • Bao T; The Affiliated Mental Health Center of Kunming Medical University, Kunming 650224, China.
  • Nie T; Department of Ultrasound, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
  • Lin J; Human Metabolomics Institute, Inc., Shenzhen 518109, China.
  • Liu P; Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
  • Zheng Y; Department of Ultrasound, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
  • Zheng X; Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China. Elec
  • Liu T; State Key Laboratory of Genetic Engineering, Department of Endocrinology and Metabolism, Institute of Metabolism and Integrative Biology, Human Phenome Institute, and School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai 200438, China. Electronic address: tiemin_liu@fudan.edu.cn.
  • Jia W; Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China; Depa
Cell Metab ; 36(5): 1000-1012.e6, 2024 May 07.
Article em En | MEDLINE | ID: mdl-38582087
ABSTRACT
The gut-brain axis is implicated in depression development, yet its underlying mechanism remains unclear. We observed depleted gut bacterial species, including Bifidobacterium longum and Roseburia intestinalis, and the neurotransmitter homovanillic acid (HVA) in individuals with depression and mouse depression models. Although R. intestinalis does not directly produce HVA, it enhances B. longum abundance, leading to HVA generation. This highlights a synergistic interaction among gut microbiota in regulating intestinal neurotransmitter production. Administering HVA, B. longum, or R. intestinalis to mouse models with chronic unpredictable mild stress (CUMS) and corticosterone (CORT)-induced depression significantly improved depressive symptoms. Mechanistically, HVA inhibited synaptic autophagic death by preventing excessive degradation of microtubule-associated protein 1 light chain 3 (LC3) and SQSTM1/p62 proteins, protecting hippocampal neurons' presynaptic membrane. These findings underscore the role of the gut microbial metabolism in modulating synaptic integrity and provide insights into potential novel treatment strategies for depression.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Depressão / Microbioma Gastrointestinal / Ácido Homovanílico / Camundongos Endogâmicos C57BL Limite: Animals / Female / Humans / Male Idioma: En Revista: Cell Metab Assunto da revista: METABOLISMO Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Estados Unidos
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Depressão / Microbioma Gastrointestinal / Ácido Homovanílico / Camundongos Endogâmicos C57BL Limite: Animals / Female / Humans / Male Idioma: En Revista: Cell Metab Assunto da revista: METABOLISMO Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Estados Unidos