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.