New findings suggest that schizophrenia may be linked to gut bacteria.

Major depressive disorder (MDD) is a highly prevalent and debilitating mental illness, which is associated with disorder of gut microbiota. However, few studies focusing on detection of the signatures of bacteria in feces of MDD patients using proteomics approach have been carried out. Here, a comparative metaproteomics analysis on the basis of an isobaric tag for relative and absolute quantification coupled with tandem mass spectrometry was carried out to explore the signature of gut microbiota in patients with MDD. Ten patients (age: 18-56 years, five women) who had MDD and a score over 20 on the Hamilton's Depression Scale and 10 healthy controls (age: 24-65 years, five women) group matched for sex, age, and BMI were enrolled. As a result, 279 significantly differentiated bacterial proteins (P<0.05) were detected and used for further bioinformatic analysis. According to phylogenetic analysis, statistically significant differences were observed for four phyla: Bacteroidetes, Proteobacteria, Firmicutes, Actinobacteria (P<0.05, for each). Abundances of 16 bacterial families were significantly different between the MDD and healthy controls (P<0.05). Furthermore, Cluster of Orthologous Groups analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that disordered metabolic pathways of bacterial proteins were mainly involved in glucose metabolism and amino acid metabolism. In conclusion, fecal microbiota signatures were altered significantly in MDD patients. Our findings provide a novel insight into the potential connection between gut microbiota and depression.

Major depressive disorder (MDD) is a serious mental illness, characterized by high morbidity, which has increased in recent decades. However, the molecular mechanisms underlying MDD remain unclear. Previous studies have identified altered metabolic profiles in peripheral tissues associated with MDD. Using curated metabolic characterization data from a large sample of MDD patients, we meta-analyzed the results of metabolites in peripheral blood. Pathway and network analyses were then performed to elucidate the biological themes within these altered metabolites. We identified 23 differentially expressed metabolites between MDD patients and controls from 46 studies. MDD patients were characterized by higher levels of asymmetric dimethylarginine, tyramine, 2-hydroxybutyric acid, phosphatidylcholine (32:1), and taurochenodesoxycholic acid and lower levels of L-acetylcarnitine, creatinine, L-asparagine, L-glutamine, linoleic acid, pyruvic acid, palmitoleic acid, L-serine, oleic acid, myo-inositol, dodecanoic acid, L-methionine, hypoxanthine, palmitic acid, L-tryptophan, kynurenic acid, taurine, and 25-hydroxyvitamin D compared with controls. L-tryptophan and kynurenic acid were consistently downregulated in MDD patients, regardless of antidepressant exposure. Depression rating scores were negatively associated with decreased levels of L-tryptophan. Pathway and network analyses revealed altered amino acid metabolism and lipid metabolism, especially for the tryptophan-kynurenine pathway and fatty acid metabolism, in the peripheral system of MDD patients. Taken together, our integrated results revealed that metabolic changes in the peripheral blood were associated with MDD, particularly decreased L-tryptophan and kynurenic acid levels, and alterations in the tryptophan-kynurenine and fatty acid metabolism pathways. Our findings may facilitate biomarker development and the elucidation of the molecular mechanisms that underly MDD.