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Selmi, H. ; Walker, A. ; Balas, L.* ; Lucio, M. ; Klotz, M. ; Jeridi, A. ; Burrichter, A.G.* ; Conti, D.V.* ; Chaffringeon, L.* ; Beinsteiner, B. ; Jasnin, M. ; Vanthuyne, N.* ; Durand, T.* ; Yildirim, A.Ö. ; Stecher, B.* ; Debarbieux, L.* ; Schmitt-Kopplin, P.

Ornithine lipids from Akkermansia muciniphila are dynamically modulated in colitis and shape macrophage inflammatory responses.

Gut Microbes 17, 2601376:2601376 (2025)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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 (OMM12) 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 α-amino group forming an amide bond with 3(R)-hydroxypalmitic acid, while the 3(R)-hydroxyl position is esterified with pentadecanoic acid. Functional studies showed that macrophages internalize and partially metabolize OL 16:0/15:0 into Nα-(3-hydroxypalmitoyl)-L-ornithine and 3(R)-hydroxypalmitic acid. In LPS-stimulated macrophages, a 1:1 mixture of OL diastereomers (3R,S + 3S,S) reduced Il6 and Il1b gene expression and decreased IL-6 secretion, without triggering IL-1β release. Interestingly, this diastereomeric mixture exhibited an opposite effect to the natural (3R,S)-epimer, which selectively promoted IL-1β secretion in LPS-primed macrophages. These results uncover a possible stereoselective modulation of IL-1β production by bacterial OLs. Overall, OL 16:0/15:0 is dynamically regulated during inflammation and may play a role in the immunomodulation of host-microbiota interactions.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Il-1β ; Oligo-mouse-microbiota ; Ornithine Lipids ; Akkermansia Muciniphila ; Citrobacter Rodentium ; Ulcerative Colitis
ISSN (print) / ISBN 1949-0976
e-ISSN 1949-0984
Journal Gut Microbes
Quellenangaben Volume: 17, Issue: 1, Pages: 2601376 Article Number: 2601376 Supplement: ,
Publisher Landes Bioscience
Reviewing status Peer reviewed
Institute(s) Research Unit BioGeoChemistry and Analytics (BGC)
Institute of Lung Health and Immunity (LHI)
Helmholtz Pioneer Campus (HPC)