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...

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans...

️ Episode 92: Genetic Loss of CFHR5 Function Protects Against Age-Related Macular Degeneration In this episode of PaperCast Base by Base, we explore a genome‑wide association and fine‑mapping study in...

Eggerthella lenta is both one of the most studied and least understood members of the human gut microbiome. Most of the interest in this Gram-positive anaerobe originates from multiple robust associations of its population with a variety of autoimmune diseases, perhaps most notably inflammatory bowel disease (IBD). The links between bacteria and inflammation are only partially known. Inflammation is driven by Th17 cells and their inflammatory cytokine IL-17, and the population of these cells is promoted by a transcription factor, RORγt. Bacterial metabolites appear to activate RORγt in a cell- and antigen-independent fashion, but the metabolites and their activating mechanism are unknown. This report describes an assay-driven search for pro-inflammatory metabolites from E. lenta that revealed a plasmalogen-triggered plasmalogen pair that forms a single molecule signal transduction device. Small electrophiles characteristic of inflammatory environments react with the plasmalogen’s sensitive vinyl ether moiety to create a lipid signal, a lysoglycoglycerolipid that upregulates the inflammatory cytokines TNF-α and IL-6 through a TLR receptor. This provides a molecular mechanism that allows E. lenta to upregulate inflammatory responses in a cell- and antigen-independent fashion. This molecular mechanism is similar to an endogenous signaling system that upregulates RORγt through a triggered mammalian plasmalogen signal, 1–18:0-lysophosphatidylethanolamine.