Reference: “Unusual Phospholipids from Morganella morganii Linked to Depression” by Sunghee Bang, Yern-Hyerk Shin, Sung-Moo Park, Lei Deng, R. Thomas Williamson, Daniel B. Graham, Ramnik J. Xavier and Jon Clardy, 16 January 2025, Journal of the American Chemical Society.
ABSTRACT: A multifactorial association study detected a probable causal connection between the prevalence of Morganella
morganii 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.
Reference: “Unusual Phospholipids from Morganella morganii Linked to Depression” by Sunghee Bang, Yern-Hyerk Shin, Sung-Moo Park, Lei Deng, R. Thomas Williamson, Daniel B. Graham, Ramnik J. Xavier and Jon Clardy, 16 January 2025, Journal of the American Chemical Society.
ABSTRACT: A multifactorial association study detected a probable causal connection between the prevalence of Morganella morganii 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.
DOI: 10.1021/jacs.4c15158 Link to the paper under discussion: https://pubs.acs.org/doi/10.1021/jacs.4c15158 PDF Link: https://pubs.acs.org/doi/epdf/10.1021/jacs.4c15158?ref=article_openPDF
Looks like IL-6 production is the mechanism of ramping up inflammatory response.