The gut microbiota is a key modulator of host immunity, in part through the production of structurally diverse and largely still uncharacterized bacterial lipids and metabolites with potential immunoregulatory properties. Using a gnotobiotic Oligo-Mouse-Microbiota (OMM(12)) mouse model infected with the Citrobacter rodentium pathogen, we investigated metabolomic changes associated with colitis. Untargeted metabolomics revealed an accumulation of host-derived lipids in the inflamed colon, while several bacterial lipid classes, including sphingolipids, glycerophospholipids, and fatty acyls were depleted. Among the bacterial lipids, ornithine-containing lipids (OLs) produced by Akkermansia muciniphila were significantly reduced during inflammation. Isolation, structural characterization, and chemical synthesis revealed OL 16:0/15:0 as a membrane-associated lipid from A. muciniphila. This lipid contains an L-ornithine head group, with its
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