Eggerthella lenta Produces a Cryptic Pro-inflammatory Lipid.

Area of Science:

• Microbiology
• Immunology
• Metabolomics

Background:

• Eggerthella lenta is a human gut bacterium linked to autoimmune diseases, including inflammatory bowel disease (IBD).
• Inflammation involves Th17 cells, IL-17, and RORγt, which can be influenced by bacterial metabolites.
• The specific metabolites and mechanisms by which gut bacteria modulate inflammation are largely unknown.

Purpose of the Study:

• To identify pro-inflammatory metabolites produced by E. lenta.
• To elucidate the molecular mechanism by which these metabolites trigger inflammatory responses.

Main Methods:

• Assay-driven screening for pro-inflammatory metabolites from E. lenta.
• Characterization of lipid signaling molecules and their interactions with cellular receptors.

Main Results:

• A plasmalogen-triggered plasmalogen pair was identified as a signaling device.
• These molecules form a lysoglycoglycerolipid that upregulates TNF-α and IL-6 via a TLR receptor.
• This mechanism operates independently of cells and antigens.

Conclusions:

• E. lenta produces a novel lipid signal that upregulates inflammatory cytokines, providing a molecular basis for its association with IBD.
• This pathway is similar to endogenous signaling systems involving plasmalogens and RORγt activation.