Gut Microbiota Characteristics In Patients With Bipolar Depression

Objective: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.Methods:Fifty-two drug-naive patients with bipolar depression were recruited from the Psychiatric Department of the First Affiliated Hospital,School of Medicine,Zhejiang University from October 2016 to August 2017.Forty-five HCs were recruited from local communities.Clinical data of all patients were collected by psychiatrist.Montgomery-Asberg Depression Rating Scale(MADRS)and 17-item Hamilton Depression Rating Scale(HDRS-17)were used to evaluate the severity of depression,and Young Manic Rating Scale(YMRS)was used to define the severity of mania.Fecal samples from all participants were stored at-80℃ within half an hour after collection between 8:30 a.m.and 10:30 a.m.after visiting the hospital.All patients received four weeks of quetiapine treatment(maintenance dose,300 mg/d),following which fecal samples were re-examined in follow-up patients.Using 16S-ribosomal RNA gene sequencing analysis,compare the differences of gut microbiota characteristics between patients with bipolar depression following quetiapine treatment and HCs.Pearson(normal distribution)or Spearman’s rho(abnormal distribution)statistic was used to estimate the association between clinical parameters and taxons.Results:Compared to healthy controls,gut microbial composition and diversity were significantly changed in BD patients.Greater diversity of gut microbiota was found in HCs compared with BD patients.Microbial composition changed following quetiapine treatment.Phylum Bacteroidetes,Proteobacteria and Firmicutes were the predominant bacterial communities respectively in untreated patients,treated patients and HCs.Lower levels of butyrate-producing bacteria were observed in both untreated and treated patients.Intriguingly,quetiapine treatment did not draw the microbial composition of patients close to that of HCs.Notably,30 microbial markers were identified on a random forest model and achieved an area under the curve(AUC)of 0.81 between untreated patients and HCs.Ten microbial markers were identified and the AUC was 0.93 between responder and non-responder patients.Conclusions:There appears to be significant alterations in gut microbiome in depressed BD patients.Gut microbiota-based biomarkers may be helpful in BD diagnosis and predicting treatment outcome.