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.

Gut microbiome disturbances have been implicated in major depressive disorder (MDD). However, little is known about how the gut virome, microbiome, and fecal metabolome change, and how they interact in MDD. Here, using whole-genome shotgun metagenomic and untargeted metabolomic methods, we identified 3 bacteriophages, 47 bacterial species, and 50 fecal metabolites showing notable differences in abundance between MDD patients and healthy controls (HCs). Patients with MDD were mainly characterized by increased abundance of the genus Bacteroides and decreased abundance of the genera Blautia and Eubacterium. These multilevel omics alterations generated a characteristic MDD coexpression network. Disturbed microbial genes and fecal metabolites were consistently mapped to amino acid (γ-aminobutyrate, phenylalanine, and tryptophan) metabolism. Furthermore, we identified a combinatorial marker panel that robustly discriminated MDD from HC individuals in both the discovery and validation sets. Our findings provide a deep insight into understanding of the roles of disturbed gut ecosystem in MDD.

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, whereas 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, 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: , identifier ChiCTR-COC-17011401, URL: .

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