Gut microbiome-wide association study of depression

Abstract Depression is one of the most poorly understood diseases due to its elusive pathogenesis. There is an urgency to identify molecular and biological mechanisms underlying depression and the gut microbiome is a novel area of interest. In this study we investigated the relation of fecal microbiome diversity and composition with depression in 1,054 from the Rotterdam Study cohort and validated these findings in the Amsterdam HELIUS cohort in 1,539 subjects. Using supervised and unsupervised machine learning approaches, we identified and replicated the association of several microbial genera. We confirm the association of genus Eggerthella, Subdoligranulum, Coprococcus and family Ruminococcaceae and identify novel bacteria including Sellimonas, Lachnoclostridium, Hungatella, Ruminococcaceae (UCG002,UCG003 and UCG005), LachnospiraceaeUCG001, Eubacterium ventriosum and Ruminococcusgauvreauiigroup associated with depression. These bacteria are known to be involved in the synthesis of glutamate, butyrate, serotonin and gamma amino butyric acid (GABA), which are key neurotransmitters for depression. Our study suggests the gut microbiome composition may play a key role in depression.