Unusual Phospholipids from <i>Morganella morganii</i> Linked to Depression

A multifactorial association study detected a probable causal connection between the prevalence of <i>Morganella morganii</i> in the gut microbiome and the incidence of major depressive disorder (MDD) in the human host. A bioassay-guided fractionation approach identified bacterially produced metabolites that induced pro-inflammatory immune responses. The metabolites are unusual phospholipids that resemble conventional cardiolipins, in which diethanolamine (DEA) replaces the central glycerol. These molecular chimeras of endogenous metabolites from phospholipid biosynthetic pathways and the industrially produced micropollutant DEA activate TLR2/TLR1 receptors and induce the production of pro-inflammatory cytokines, especially IL-6. Their activity in conventional immunomodulatory assays largely parallels that of immunogenic cardiolipins with conventional structures. The molecular mechanism connecting these chimeric cardiolipins to MDD is supported by other studies and has implications for conditions other than MDD.