Jielan Mi,Tana He,Xinyun Hu,Zhihao Wang,Tingting Wang,Xiaole Qi,Kai Li,Li Gao,Changjun Liu,Yanping Zhang,Suyan Wang,Yu Qiu,Zengqi Liu,Jie Song,Xiaomei Wang,Yulong Gao,Hongyu Cui

Int J Antimicrob Agents.2023 Sep 25:106969.doi: 10.1016/j.ijantimicag.2023.106969. Online ahead of print.

Abstract

Commensal bacteria can modulate acute immune responses against infections in hosts. In this study, we screened and obtained Enterococcus faecium C171, a strain with basic characteristics similar to that of the reference probiotic, which has strong anti-inflammatory and anti-infective effects. It can inhibit the production of pro-Caspase-1 and significantly reduce the production of interleukin-1β (IL-1β) in vitro. These reactions were further confirmed using the transwell system. Live E. faecium C171 mainly exerted an inhibitory effect on acute inflammation, while the anti-infective and immune-activating effects were mainly mediated by the E. faecium C171-produced bacterial extracellular vesicles (Efm-C171-BEVs). Furthermore, in the specific pathogen-free (SPF) chicken model, oral administration of E. faecium C171 increased the relative abundance of beneficial microbiota (Enterococcus and Lactobacillus), especially Enterococcus, the most important functional bacteria of the gut microbiota. E. faecium C171 significantly inhibited the acute inflammatory response, induced by a highly virulent infectious disease, and reduced mortality in SPF chickens by 75%. Meanwhile, E. faecium C171 induced high levels of CD3+CD4-CD8-immunoregulatory and CD8+ killer T cells, and significantly improved the proliferative activity of T cells (in peripheral blood mononuclear cells) and the secretion of interferon-γ. These findings demonstrate that E. faecium C171 and Efm-C171-BEVs are promising candidate adjuvant therapeutic agents for the treatment of various acute inflammatory diseases and acute viral infections.

Keywords: Enterococcus faecium; IBDV; acute inflammation; anti-infective; anti-inflammatory; bacterial extra vesicles; immunomodulatory; probiotics.