Evaluation of the therapeutic effect and dose–effect of Bifidobacterium breve on the primary Clostridioides difficile infected mice

Probiotics are widely used as an adjuvant agent for the prevention of primary Clostridioides difficile infection (pCDI) and are less commonly used in the treatment of pCDI. Here, the different doses of Bifidobacterium breve YH68 were used to treat the pCDI mouse model and the actual therapeutic effect was evaluated. Fecal samples of pCDI mice were collected from the pre-infection, post-infection, and post-treatment stages. Simultaneous 16S rRNA amplicon sequencing and non-targeted metabolite assays were performed on these mouse feces, followed by correlation analysis. We found that high doses of B. breve YH68 exerted prominent therapeutic effects and no side effects in pCDI mice, resulted in a high survival rate, accompanied by a dose–effect relationship. YH68 enhanced the levels of caffeine, butyric acid, secondary bile acids in the feces of pCDI mice and significantly upregulated the abundance of genera associated with these metabolites, including Akkermansia , Coprococcus , Oscillospira , and Ruminococcus . Meanwhile, YH68 downregulated the levels of cortisol and phytosphingosine, and these metabolites were positively correlated with the abundance of the Klebsiella and Pseudomonas genera. These findings indicated that YH68 has outstanding therapeutic effects on the pCDI mouse model and is expected to be a potential new option for clinical pCDI therapy. Key points • Bifidobacterium breve YH68 has therapeutic effects on the pCDI mice and was accompanied by a dose–effect relationship. • Bifidobacterium breve YH68 enhanced the levels of caffeine, butyric acid, secondary bile acids in the feces of pCDI mice after treatment, as well as upregulated the abundance of beneficial microbes. • Bifidobacterium breve YH68 decreased the levels of cortisol and phytosphingosine and downregulated the abundance of harmful microbes. Graphical abstract