Immunometabolic reprogramming of macrophages by gut microbiota-derived cadaverine controls colon inflammation
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.
Authors
- Antonin Lamazière (ORCID: https://orcid.org/0000-0003-0813-7370)
- Laura Creusot (ORCID: https://orcid.org/0000-0002-3882-8423)
- Hang‐Phuong Pham (ORCID: https://orcid.org/0000-0002-7896-7401)
- Guillaume Chevreux (ORCID: https://orcid.org/0000-0003-3452-2125)
- Rafael J. Argüello (ORCID: https://orcid.org/0000-0001-9785-3883)
- Rodrigo de Oliveira Formiga (ORCID: https://orcid.org/0000-0001-5475-0067)
- Clément Pontoizeau (ORCID: https://orcid.org/0000-0002-3275-2851)
- Tatiana Ledent (ORCID: https://orcid.org/0000-0002-6988-8779)
- Marius Bredon (ORCID: https://orcid.org/0000-0001-7396-8870)
- Patrick Emond (ORCID: https://orcid.org/0000-0002-5324-2164)
- Camille Danne (ORCID: https://orcid.org/0000-0003-0971-8310)
- Virginie Puchois
- Gerhard Krönke (ORCID: https://orcid.org/0000-0002-7566-4325)
- Iria Alonso Salgueiro
- Marie‐Laure Michel (ORCID: https://orcid.org/0000-0003-2657-4662)
- Cyril Scandola (ORCID: https://orcid.org/0000-0002-5305-9095)
- Nathalie Rolhion (ORCID: https://orcid.org/0000-0002-2946-4808)
- Timothy Wai (ORCID: https://orcid.org/0000-0002-6770-6222)
- Harry Sokol (ORCID: https://orcid.org/0000-0002-2914-1822)
- Márcio A. C. Ribeiro (ORCID: https://orcid.org/0000-0002-8431-4968)
- Léonard Dubois (ORCID: https://orcid.org/0000-0003-0322-482X)
- Loïc Chollet
- Qing Li (ORCID: https://orcid.org/0000-0002-0169-8098)
- Yining Zhao (ORCID: https://orcid.org/0009-0006-4828-5254)
- Jean-Philippe Auger
- Salomé Amouyal
- Emma Tkacz
- Perle Guarino-Vignon
- Rand Fatouh
Institutions
- Université de Tours (FR)
- Délégation Paris 5 (FR)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Institut Pasteur (FR)
- Université Paris Cité (FR)
- Université Paris-Saclay (FR)
- Microbiologie de l’alimentation au service de la santé (FR)
- Sorbonne Université (FR)
- Universitätsklinikum Erlangen (DE)
- Assistance Publique – Hôpitaux de Paris (FR)
- Institut Jacques Monod (FR)
- Centre Hospitalier de Saint-Malo (FR)
- Centre de Recherche Saint-Antoine (FR)
- Centre d’Immunologie de Marseille-Luminy (FR)
- Institut des Maladies Génétiques Imagine (FR)
Publication Details
- Journal
- Cell Host & Microbe
- Published
- 2025-10-01
- DOI
- https://doi.org/10.1016/j.chom.2025.09.009
- Citations
- 7
- Primary Topic
- Clinical Nutrition and Gastroenterology
- Type
- article
- Field-Weighted Citation Impact
- 7.84