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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Psychiatry | doi: 10.3389/fpsyt.2019.00784

Gut microbiota in bipolar depression and its relationship to brain function: an advanced exploration

 QiaoQiao Lu1, 2,  Jianbo Lai1, 3, 4,  Hai-Feng Lu5,  Chee Ng6,  TingTing Huang1,  Hua Zhang5, Jiajun Jiang1, Jianbo Hu1, 3, 4,  Jing Lu1, 3, 4, Shaojia Lu1, 3, 4, Tingting Mou1, 3, 4, Dandan Wang1, 3, 4,  Yanli Du1, Caixi Xi1,  Hailong Lyu1, 3, 4,  Chen Jingkai1, 3, 4,  Yi Xu1, 3, 4 and  Shaohua Hu1, 3, 4*
  • 1Department of Psychiatry, First Affiliated Hospital, College of Medicine, Zhejiang University, China
  • 2Hangzhou Seventh Peoples Hospital, China
  • 3Zhejiang Key Laboratory of Mental Disorders Diagnosis and Treatment Technology, China
  • 4Brain Research Institute, Zhejiang University, China
  • 5State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, China
  • 6The Melbourne Clinic, Australia

The mechanism of bipolar disorder is unclear. Growing evidence indicates that gut microbiota plays a pivotal role in mental disorders. This study aimed to find out changes in the gut microbiota in bipolar depression (BD) subjects following treatment with quetiapine, and evaluate their correlations with the brain and immune function. Totally 36 subjects with BD and 27 healthy controls (HCs) were recruited. The severity of depression was evaluated with the Montgomery–Asberg Depression Rating Scale (MADRS). At baseline, fecal samples were collected and analyzed by quantitative polymerase chain reaction (qPCR). T lymphocyte subsets were measured to examine immune function. Near-infrared spectroscopy (NIRS) was used to assess brain function. All BD subjects received quetiapine treatment (300 mg/d) for four weeks, following which the fecal microbiota and immune profiles were reexamined. Here, we first put forward the new concept of brain-gut coefficient of balance (B-GCB), which referred to the ratio of [oxygenated hemoglobin]/(Bifidobacteria to Enterobacteriaceae ratio), to analyze the linkage between the gut microbiota and brain function. At baseline, the CD3+ T cell proportion was positively correlated with log10 Enterobacter spp count, while the correlativity between the other bacteria and immune profiles were negative. Log10 B-GCB was positively correlated with CD3+ T cell proportion. In subjects with BD, counts of Faecalibacterium prausnitzii, Bacteroides–Prevotella group, Atopobium Cluster, Enterobacter spp and Clostridium Cluster IV were higher, while the log10 (B/E) were lower than HCs (B/E refers to Bifidobacteria to Enterobacteriaceae ratio, and represents microbial colonization resistance). After treatment, MADRS scores were reduced while the levels of Eubacterium rectale, Bifidobacteria and B/E increased. The composition of the gut microbiota and its relationship to brain function were altered in BD subjects. Quetiapine treatment was effective for depression and influenced the composition of gut microbiota in patients.
Clinical trial registration:, identifier: ChiCTR-COC-17011401, URL:

Keywords: Bipolar depression, Gut Microbiota, brain function, Immune function, quetiapine treatment 3

Received: 28 Aug 2019; Accepted: 02 Oct 2019.

Copyright: © 2019 Lu, Lai, Lu, Ng, Huang, Zhang, Jiang, Hu, Lu, Lu, Mou, Wang, Du, Xi, Lyu, Jingkai, Xu and Hu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Shaohua Hu, First Affiliated Hospital, College of Medicine, Zhejiang University, Department of Psychiatry, Hangzhou, 310016, Zhejiang Province, China,