Anxiolytic effects of Akkermansia muciniphila in acute stress restraint and its mechanism of action

ZHU Yuhao; ZHANG Di; WANG Yongxiang; LI Xingang

doi:10.13506/j.cnki.jpr.2025.09.002

Abstract：Objective To observe the anxiolytic effects of live mucin and inactivated bacteria on Akkermansia muci-niphila(Akk)in acute stress bondage,and to preliminarily explore the mechanism of action.Methods Thirty C57 male mice were randomly divided into a normal group(100 μL·d-1 normal saline per mouse by gavage),a live Akkermansia mu-ciniphila group(100 pL·d-1 live Akk per mouse by gavage),and a killed Akkermansia muciniphila group(100 μL·d-1 killed Akk per mouse by gavage).After continuous gavage for 30 days,the open field test(OFT),elevated plus maze(EPM)and light dark box(LDB)were used to detect the anxiolytic effects of live and killed Akk bacteria under baseline conditions and acute stress restraint conditions.Metagenomic 16S rDNA diversity sequencing was used to detect the coloniza-tion of live Akk bacteria and the influence of intestinal flora.Immunofluorescence experiments were used to detect the chan-ges in the activity of specific anxiety brain areas after gavage of live and killed Akk bacteria.Results Compared with the normal group,the duration and frequency of open-arm residence in the EPM model were significantly increased in the Akk inactivated bacteria gavage(P＜0.01),and the time and frequency of entering the open box in the LDB model were signifi-cantly increased(P＜0.05).The c-fos activation point of amygdala-related brain regions in mice,especially BLA,was sig-nificantly reduced(P＜0.05).Conclusion Akk-inactivated bacteria have anxiolytic effects in the state of acute stress bondage,which is related to the stability of the internal structure of the microbiota and the regulation of the activity of the a-mygdala-related regions of mice.