Gut Microbiota in Bipolar Depression and Its Relationship to Brain Function: An Advanced Exploration

Qiaoqiao Lu; Jianbo Lai; Haifeng Lu; Chee Ng; Tingting Huang; Hua Zhang; Kaijing Ding; Zheng Wang; Jiajun Jiang; Jianbo Hu; Jing Lu; Shaojia Lu; Tingting Mou; Dandan Wang; Yanli Du; Caixi Xi; Hailong Lyu; Jingkai Chen; Yi Xu; Zhuhua Liu; Shaohua Hu

doi:10.3389/fpsyt.2019.00784

Gut Microbiota in Bipolar Depression and Its Relationship to Brain Function: An Advanced Exploration

Front Psychiatry. 2019 Oct 29:10:784. doi: 10.3389/fpsyt.2019.00784. eCollection 2019.

Authors

Qiaoqiao Lu^{1

2}, Jianbo Lai^{1

3

4}, Haifeng Lu⁵, Chee Ng⁶, Tingting Huang¹, Hua Zhang⁵, Kaijing Ding⁷, Zheng Wang^{1

3

4}, Jiajun Jiang¹, Jianbo Hu^{1

3

4}, Jing Lu^{1

3

4}, Shaojia Lu^{1

3

4}, Tingting Mou^{1

3

4}, Dandan Wang^{1

3

4}, Yanli Du¹, Caixi Xi¹, Hailong Lyu^{1

3

4}, Jingkai Chen^{1

3

4}, Yi Xu^{1

3

4}, Zhuhua Liu⁸, Shaohua Hu^{1

3

4}

Affiliations

¹ Department of Psychiatry, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
² Department of Psychiatry, Hangzhou Seventh People's Hospital, Hangzhou, China.
³ The Key Laboratory of Mental Disorder Management of Zhejiang Province, Hangzhou, China.
⁴ Brain Research Institute, Zhejiang University, Hangzhou, China.
⁵ State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁶ The Melbourne Clinic, Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia.
⁷ Department of Children and Adolescents' Psychology, Hangzhou Seventh People's Hospital, Hangzhou, China.
⁸ Center of Mental Health, General Hospital of Ningxia Medical University, Yinchuan, China.

Abstract

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-G_CB), 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, whereas the correlativity between the other bacteria and immune profiles were negative. Log₁₀ B-G_CB 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, whereas 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, whereas 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: http://www.chictr.org.cn/index.aspx, identifier ChiCTR-COC-17011401, URL: http://www.chictr.org.cn/listbycreater.aspx.

Keywords: bipolar depression; brain function; gut microbiota; immune function; quetiapine treatment.