Objective：We used enterotoxigeni Escherichia coli(ETEC)to build the diarrhea model induced by intestinal flora dysfunction. Then the probiotics Akkermansia muciniphila(A. muciniphila)was used to analyze the protective effect in the diarrhea. Methods：The diarrhea model of mice was induced by ETEC. The experimental mice were randomly divided into PBS group，ETEC model group and A. muciniphila treatment group. Each mouse of the A. muciniphila treatment group was treated with A. muciniphila solution(1×109 CFU/mL)0.2 mL/d for 5 days，and the model group was gavaged with ETEC solution(concentration 1×109 CFU/mL) 0.5 mL/d for 5 days. The changes of physical condition，body weight，diarrhea rate and mortality of mice were recorded；the pathological changes of colon tissue were observed using HE staining；the contents of serum interleukin(IL)-1β，IL-6 and tumor necrosis factor-α (TNF-α)were detected using ELISA method；the expression of IL-1，TNF-α and IL-6 mRNA in colon tissue were detected by RT-PCR； and the feces of mice were collected for 16S rRNA high-throughput sequencing and statistical analysis. Results：Compared with the ETEC model group，the physical condition of the A. muciniphila treatment group was significantly improved，the diarrhea rate was reduced by 66%，the mortality rate was reduced by 30%，and the contents of serum IL - 1β，IL - 6 and TNF - α were significantly decreased. The contents of IL-1 mRNA，IL-6 mRNA and TNF-α mRNA in colon tissue were significantly decreased. The pathological changes of colon tissue were significantly improved. 16S rRNA sequencing showed that the relative abundance of species increased significantly，the α diversity and the composition of intestinal microflora changed significantly in the A. muciniphila treatment group. In the A. muciniphila treatment group，the abundance of multiple probiotics increased. Conclusion：Probiotics A. muciniphila can relieve diarrhea caused by ETEC through increasing intestinal flora diversity，protecting colonic mucosa and reducing the expression of inflammatory factors.
