Immunometabolic reprogramming of macrophages by gut microbiota-derived cadaverine controls colon inflammation
Year: 2025
Type: article
Abstract: Cadaverine is a polyamine produced by the gut microbiota with links to health and disease, notably inflammatory bowel disease (IBD). Here, we show that cadaverine shapes monocyte-macrophage immunometabolism in a context- and concentration-dependent fashion to impact macrophage functionality. At baseline, cadaverine is taken up via L-lysine transporters and activates the thioredoxin system, while during inflammation, cadaverine signals through aconitate decarboxylase 1 (Acod1)-itaconate. Both pathways induce activation of transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), which supports mitochondrial respiration and promotes immunoregulatory macrophage polarization. Conversely, under higher concentrations, cadaverine acts via histamine 4 receptor, leading to glycolysis-driven inflammation and pro-inflammatory functions in macrophages. Likewise, cadaverine exhibits paradoxical effects in experimental colitis, either protective or detrimental, evoking opposite fates on macrophages depending on levels dictated by Enterobacteriaceae. In IBD patients, elevated cadaverine correlated with higher flare risk. Our findings implicate cadaverine as a microbiota-derived metabolite manipulating macrophage energy metabolism with consequences in intestinal inflammation and implications for IBD pathogenesis.
Source: Cell Host & Microbe
Authors: Rodrigo de Oliveira Formiga, Qing Li, Yining Zhao, Márcio Augusto Campos Ribeiro, Perle Guarino-Vignon, Rand Fatouh, Leonard Dubois, Laura Creusot, Virginie Puchois, Salomé Amouyal, Iria Alonso Salgueiro, Marius Bredon, Loïc Chollet, Tatiana Ledent, Cyril Scandola, Jean-Philippe Auger, Camille Danne, Gerhard Krönke, Emma Tkacz, Patrick Emond, Guillaume Chevreux, Hang Phuong Pham, Clément Pontoizeau, Antonin Lamaziere, Rafael José Argüello, Nathalie Rolhion, Marie-Laure Michel, Timothy Wai, Harry Sokol
Institutions: Inserm, Sorbonne Université, Assistance Publique – Hôpitaux de Paris, Centre de Recherche Saint-Antoine, Centre National de la Recherche Scientifique, Institut Pasteur, Université Paris Cité, Biologie cellulaire physiologique et pathologique, AgroParisTech, Université Paris-Saclay, Microbiologie de l’alimentation au service de la santé, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, German Rheumatism Research Centre, Charité - Universitätsmedizin Berlin, Université de Tours, Analyse des Systèmes Biologiques, Institut Jacques Monod, Institut des Maladies Génétiques Imagine, Aix-Marseille Université, Centre d’Immunologie de Marseille-Luminy, Hôpital Saint-Antoine
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
OpenAlex ID: W4414780309