Bacteriocin Microcin J25’s antibacterial infection effects and novel non-microbial regulatory mechanisms: differential regulation of dopaminergic receptors  

作　　者：Lijun Shang Fengjuan Yang Qingyun Chen Ziqi Dai Guangxin Yang Xiangfang Zeng Shiyan Qiao Haitao Yu 

机构地区：[1]Department of Animals Sciences,College of Animal Sciences,Jilin University,Changchun 130062,China [2]State Key Laboratory of Animal Nutrition and Feeding,Ministry of Agriculture and Rural Affairs Feed Industry Centre,China Agricultural University,Beijing 100193,P.R.China [3]Beijing Bio-feed additives Key Laboratory,Beijing 100193,P.R.China

出　　处：《Journal of Animal Science and Biotechnology》2025年第2期813-830,共18页畜牧与生物技术杂志(英文版)

基　　金：supported by the National Key Research and Development Program of China(Grant number 32030105);National Pig Technology Innovation Center Leading Technology Projects(NCTIP XD/B05);Beijing Innovation Consortium of Livestock Research System(BAIC05-2024).

摘　　要：Background The antibacterial and immunomodulatory activities of bacteriocins make them attractive targets for development as anti-infective drugs.Although the importance of the enteric nervous system(ENS)in the struggle against infections of the intestine has been demonstrated,whether it is involved in bacteriocins anti-infective mecha-nisms is poorly defined.Results Here,we demonstrated that the bacteriocin Microcin J25(J25)significantly alleviated diarrhea and intesti-nal inflammation in piglets caused by enterotoxigenic Escherichia coli(ETEC)infection.Mechanistically,macrophage levels were significantly downregulated after J25 treatment,and this was replicated in a mouse model.Omics analysis and validation screening revealed that J25 treatment induced significant changes in the dopaminergic neuron pathway,but little change in microbial structure.The alleviation of inflammation may occur by down-regulating dopamine receptor(DR)D1 and the downstream DAG-PKC pathway,thus inhibiting arachidonic acid decomposition,and the inhibition of macrophages may occur through the up-regulation of DRD5 and the downstream cAMP-PKA pathway,thus inhibiting NF-κB.Conclusions Our studies’findings provide insight into the changes and possible roles of the ENS in J25 treatment of ETEC infection,providing a more sophisticated foundational understanding for developing the application poten-tial of J25.

关 键 词：Arachidonic acid Dopaminergic receptors Enteric nervous system MACROPHAGE MICROBIOTA Microcins 

分 类 号：S852.2[农业科学—基础兽医学] R965[农业科学—兽医学]