BibTex format
@article{Chilloux:2025:10.1038/s42255-025-01413-8,
author = {Chilloux, J and Brial, F and Everard, A and Smyth, D and Andrikopoulos, P and Zhang, L and Plovier, H and Myridakis, A and Hoyles, L and Moreno-Navarrete, JM and Luque, JL and Casagrande, V and Menghini, R and Ahmetaj-Shala, B and Blancher, C and Martinez-Gili, L and Gencer, S and Fearnside, JF and Barton, RH and Neves, AL and Rothwell, AR and Gérard, C and Calderari, S and Williamson, MJ and Fuchs, JE and Govada, L and Boulangé, CL and Patel, S and Scott, J and Thursz, M and Chayen, N and Glen, RC and Gooderham, NJ and Nicholson, JK and Federici, M and Fernández-Real, JM and Gauguier, D and Liu, PP and Cani, PD and Dumas, M-E},
doi = {10.1038/s42255-025-01413-8},
journal = {Nat Metab},
pages = {2531--2547},
title = {Inhibition of IRAK4 by microbial trimethylamine blunts metabolic inflammation and ameliorates glycemic control.},
url = {http://dx.doi.org/10.1038/s42255-025-01413-8},
volume = {7},
year = {2025}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - The global type 2 diabetes epidemic is a major health crisis. Although the microbiome has roles in the onset of insulin resistance (IR), low-grade inflammation and diabetes, the microbial compounds controlling these processes remain to be discovered. Here, we show that the microbial metabolite trimethylamine (TMA) decouples inflammation and IR from diet-induced obesity by inhibiting interleukin-1 receptor-associated kinase 4 (IRAK4), a central kinase in the Toll-like receptor pathway sensing danger signals. TMA blunts TLR4 signalling in primary human hepatocytes and peripheral blood monocytic cells and rescues mouse survival after lipopolysaccharide-induced septic shock. Genetic deletion and chemical inhibition of IRAK4 result in metabolic and immune improvements in high-fat diets. Remarkably, our results suggest that TMA-unlike its liver co-metabolite trimethylamine N-oxide, which is associated with cardiovascular disease-improves immune tone and glycemic control in diet-induced obesity. Altogether, this study supports the emerging role of the kinome in the microbial-mammalian chemical crosstalk.
AU - Chilloux,J
AU - Brial,F
AU - Everard,A
AU - Smyth,D
AU - Andrikopoulos,P
AU - Zhang,L
AU - Plovier,H
AU - Myridakis,A
AU - Hoyles,L
AU - Moreno-Navarrete,JM
AU - Luque,JL
AU - Casagrande,V
AU - Menghini,R
AU - Ahmetaj-Shala,B
AU - Blancher,C
AU - Martinez-Gili,L
AU - Gencer,S
AU - Fearnside,JF
AU - Barton,RH
AU - Neves,AL
AU - Rothwell,AR
AU - Gérard,C
AU - Calderari,S
AU - Williamson,MJ
AU - Fuchs,JE
AU - Govada,L
AU - Boulangé,CL
AU - Patel,S
AU - Scott,J
AU - Thursz,M
AU - Chayen,N
AU - Glen,RC
AU - Gooderham,NJ
AU - Nicholson,JK
AU - Federici,M
AU - Fernández-Real,JM
AU - Gauguier,D
AU - Liu,PP
AU - Cani,PD
AU - Dumas,M-E
DO - 10.1038/s42255-025-01413-8
EP - 2547
PY - 2025///
SP - 2531
TI - Inhibition of IRAK4 by microbial trimethylamine blunts metabolic inflammation and ameliorates glycemic control.
T2 - Nat Metab
UR - http://dx.doi.org/10.1038/s42255-025-01413-8
UR - https://www.ncbi.nlm.nih.gov/pubmed/41361024
VL - 7
ER -
