PuSH - Publication Server of Helmholtz Zentrum München: Ornithine lipids from <em>Akkermansia muciniphila</em> are dynamically modulated in colitis and shape macrophage inflammatory responses.

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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 (2025)

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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 N^α-(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; Citrobacter-rodentium; Sphingolipids; Pathogenesis; Bacteria

ISSN (print) / ISBN 1949-0976

e-ISSN 1949-0984

Journal Gut Microbes

Quellenangaben Volume: 17, Issue: 1, Article Number: 2601376

Publisher Landes Bioscience

Publishing Place 530 Walnut Street, Ste 850, Philadelphia, Pa 19106 Usa

Reviewing status Peer reviewed

Institute(s) Research Unit BioGeoChemistry and Analytics (BGC)
Institute of Lung Health and Immunity (LHI)
Helmholtz Pioneer Campus (HPC)

Grants Agence Nationale de la Recherche (ANR)
French Agence Nationale de la Recherche
Deutsche Forschungsgemeinschaft