de Oliveira Formiga R, Li Q, Zhao Y, Campos Ribeiro MA, Guarino-Vignon P, Fatouh R, Dubois L, Creusot L, Puchois V, Amouyal S, Alonso Salgueiro I, Bredon M, Chollet L, Ledent T, Scandola C, Auger JP, Danne C, Krönke G, Tkacz E, Emond P, Chevreux G, Pham HP, Pontoizeau C, Lamaziere A, Argüello RJ, Rolhion N, Michel ML, Wai T, Sokol H (2025)
Publication Type: Journal article
Publication year: 2025
Book Volume: 33
Pages Range: 1855-1872.e10
Journal Issue: 11
DOI: 10.1016/j.chom.2025.09.009
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.
APA:
de Oliveira Formiga, R., Li, Q., Zhao, Y., Campos Ribeiro, M.A., Guarino-Vignon, P., Fatouh, R.,... Sokol, H. (2025). Immunometabolic reprogramming of macrophages by gut microbiota-derived cadaverine controls colon inflammation. Cell Host & Microbe, 33(11), 1855-1872.e10. https://doi.org/10.1016/j.chom.2025.09.009
MLA:
de Oliveira Formiga, Rodrigo, et al. "Immunometabolic reprogramming of macrophages by gut microbiota-derived cadaverine controls colon inflammation." Cell Host & Microbe 33.11 (2025): 1855-1872.e10.
BibTeX: Download