Scientists have identified 3 bacteriophages, 47 bacterial species, and 50 fecal metabolites that were significantly more or less abundant in people with major depressive disorder (MDD) compared with healthy controls, according to a study in 311 individuals. The findings provide evidence that MDD may be characterized by gut microbiome disturbances. Jian Yang and colleagues also developed a marker panel based on the bacterial, viral, and metabolic MDD signatures they uncovered, which effectively differentiated between patients with MDD and controls. A similar biomarker-based diagnostic tool may help physicians better diagnose MDD, offering a companion to clinical interviews, which frequently result in misdiagnosis. While previous studies have observed gut microbiome disturbances in people with MDD, researchers had not yet identified the bacterial species that differ in people with this common mental disorder or explored whether intestinal viruses are also disrupted in MDD. To learn more about how MDD specifically affects microbial and viral communities in the gut, as well as fecal metabolic signatures, Yang et al. analyzed genetic material from 311 fecal samples taken from 156 patients with MDD and 155 healthy controls and performed large-scale gas chromatography-mass spectrometry-based analyses of the fecal metabolites. The researchers found distinct differences in the bacterial composition of MDD patients compared with controls, observing that they contained higher levels of bacterial species belonging to the genus Bacteroides and lower levels of species belonging to Blautia and Eubacterium. A greater Bacteroides presence in the gut microbiome could account for previous observations that people with MDD have higher cytokine levels and increased inflammation, while fewer Blautia would result in a loss of anti-inflammatory benefits. Although Yang et al. did not find significant differences between the viral composition of the MDD and control groups, they did identify 3 bacteriophages that were less abundant in MDD patients. The authors suggest future studies explore the role of these phages.