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Adv Sci (Weinh). 2019 May 15;6(14):1900752. doi: 10.1002/advs.201900752. eCollection 2019 Jul 17.

Gut Microbiota Changes in Patients with Bipolar Depression.

Hu S1,2,3, Li A4, Huang T5, Lai J1,2,3, Li J6,7, Sublette ME8, Lu H6, Lu Q5, Du Y5, Hu Z9, Ng CH10, Zhang H6, Lu J1,2,3, Mou T1,2,3, Lu S1,2,3, Wang D1,2,3, Duan J1,2,3, Hu J1,2,3, Huang M1,2,3, Wei N1,2,3, Zhou W1,2,3, Ruan L11, Li MD6,7, Xu Y1,2,3.

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Department of Psychiatry First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China.
The Key Laboratory of Mental Disorder's Management of Zhejiang Province No. 79, Qingchun Road Hangzhou 310003 China.
Brain Research Institute of Zhejiang University Hangzhou 310003 China.
Henan Gene Hospital The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052 China.
Zhejiang University School of Medicine Hangzhou 310058 China.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases The First Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310003 China.
Research Center for Air Pollution and Health Zhejiang University Hangzhou 310003 China.
Department of Psychiatry Columbia University New York NY 10032 USA.
Department of Obstetrics & Gynecology Hangzhou Red Cross Hospital Hangzhou 310003 China.
The Melbourne Clinic Department of Psychiatry University of Melbourne Melbourne Victoria 3052 Australia.
Department of Mental Health Ningbo First Hospital Ningbo 315010 China.


This study aims to characterize the gut microbiota in depressed patients with bipolar disorder (BD) compared with healthy controls (HCs), to examine the effects of quetiapine treatment on the microbiota, and to explore the potential of microbiota as a biomarker for BD diagnosis and treatment outcome. Analysis of 16S-ribosomal RNA gene sequences reveals that gut microbial composition and diversity are significantly different between BD patients and HCs. Phylum Bacteroidetes and Firmicutes are the predominant bacterial communities in BD patients and HCs, respectively. Lower levels of butyrate-producing bacteria are observed in untreated patients. Microbial composition changes following quetiapine treatment in BD patients. Notably, 30 microbial markers are identified on a random forest model and achieve an area under the curve (AUC) of 0.81 between untreated patients and HCs. Ten microbial markers are identified with the AUC of 0.93 between responder and nonresponder patients. This study characterizes the gut microbiota in BD and is the first to evaluate microbial changes following quetiapine monotherapy. Gut microbiota-based biomarkers may be helpful in BD diagnosis and predicting treatment outcome, which need further validations.


16S rRNA gene sequence; biomarkers; bipolar disorder; gut microbiota; quetiapine

Conflict of interest statement

The authors declare no conflict of interest.

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