Immunometabolic reprogramming of macrophages by gut microbiota-derived cadaverine controls colon inflammation
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.
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BibTeX
@article{formiga2026immunometabolic,
title = {{Immunometabolic reprogramming of macrophages by gut microbiota-derived cadaverine controls colon inflammation}},
author = {Rodrigo de Oliveira Formiga and Qing Li and Yining Zhao and Márcio Augusto Campos Ribeiro and Perle Guarino-Vignon and Rand Fatouh and Leonard Dubois and Laura Creusot and Virginie Puchois and Salomé Amouyal and Iria Alonso Salgueiro and Marius Bredon and Loïc Chollet and Tatiana Ledent and Cyril Scandola and Jean-Philippe Auger and Camille Danne and Gerhard Krönke and Emma Tkacz and Patrick Emond and Guillaume Chevreux and Hang Phuong Pham and Clément Pontoizeau and Antonin Lamaziere and Rafael José Argüello and Nathalie Rolhion and Marie-Laure Michel and Timothy Wai and Harry Sokol},
journal = {Cell Host \& Microbe},
year = {2026},
month = nov,
doi = {10.1016/j.chom.2025.09.009},
url = {https://hal.science/hal-05848895v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Immunometabolic reprogramming of macrophages by gut microbiota-derived cadaverine controls colon inflammation
AU - Rodrigo de Oliveira Formiga
AU - Qing Li
AU - Yining Zhao
AU - Márcio Augusto Campos Ribeiro
AU - Perle Guarino-Vignon
AU - Rand Fatouh
AU - Leonard Dubois
AU - Laura Creusot
AU - Virginie Puchois
AU - Salomé Amouyal
AU - Iria Alonso Salgueiro
AU - Marius Bredon
AU - Loïc Chollet
AU - Tatiana Ledent
AU - Cyril Scandola
AU - Jean-Philippe Auger
AU - Camille Danne
AU - Gerhard Krönke
AU - Emma Tkacz
AU - Patrick Emond
AU - Guillaume Chevreux
AU - Hang Phuong Pham
AU - Clément Pontoizeau
AU - Antonin Lamaziere
AU - Rafael José Argüello
AU - Nathalie Rolhion
AU - Marie-Laure Michel
AU - Timothy Wai
AU - Harry Sokol
PY - 2026
DA - 2026/11/02
JO - Cell Host & Microbe
DO - 10.1016/j.chom.2025.09.009
UR - https://hal.science/hal-05848895v1
AB - 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.
SN - 1931-3128
ER -