Bacterial indole-3-propionic acid inhibits macrophage IL-1βproduction through targeting methionine metabolism  

作　　者：Ziyi Han Jian Fu Aiyan Gong Wenkai Ren 

机构地区：[1]State Key Laboratory of Livestock and Poultry Breeding,College of Animal Science,South China Agricultural University,Guangzhou,510642,China [2]China Institute of Veterinary Drug Control,Beijing,100081,China [3]Animal Disease-resistant Nutrition,Key Laboratory of Sichuan Province,Sichuan Agricultural University,Chengdu,625014,China

出　　处：《Science China(Life Sciences)》2025年第4期1118-1131,共14页中国科学(生命科学英文版)

基　　金：supported by the National Natural Science Foundation of China(32225047,U22A20510);Double First-Class Discipline Promotion Project(2023B10564001);National Center of Technology Innovation for Pigs(NCTIP-XD/B13);the Open Project Program of Sichuan Provincial Key Laboratory of Animal Disease-resistant Nutrition,Sichuan Agricultural University(SZ202301-02)。

摘　　要：The gut microbiota plays key roles in host health by shaping the host immune responses through their metabolites,like indole derivatives from tryptophan.However,the direct role of these indole derivatives in macrophage fate decision and the underlying mechanism remains unknown.Here,we found that bacterial indole-3-propionic acid(IPA)downregulates interleukin-1beta(IL-1β)production in M1 macrophages through inhibition of nuclear factor-kappa B(NF-κB)signaling.Mechanistically,IPA binds specifically with methionine adenosyltransferase 2A(MAT2A)to promote S-adenosylmethionine(SAM)synthesis,which facilitates the DNA methylation of ubiquitin-specific peptidase 16(USP16,a deubiquitinase),and in turn promotes Toll-like receptor 4(TLR4)ubiquitination and NF-κB inhibition.Furthermore,IPA administration attenuates sepsis in mouse models induced by lipopolysaccharides(LPS),showcasing its potential as a microbial-derived adjunct in alleviating inflammation.Collectively,our findings reveal a newly found microbial metabolite-immune system regulatory pathway mediated by IPA.

关 键 词：IPA MACROPHAGE MAT2A IL-1Β 

分 类 号：R392[医药卫生—免疫学]