A strain of Bacteroides thetaiotaomicron attenuates colonization of Clostridioides difficile and affects intestinal microbiota and bile acids profile in a mouse model

Clostridioides difficile infection (CDI) is a growing global public health threat. While fecal microbiota transplantation (FMT) is an effective therapy for CDI, a number of challenges limit its application. Studies suggest that probiotics may be a promising alternative therapy. In the current study, we evaluated whether Bacteroides thetaiotaomicron (B. thetaiotaomicron) would inhibit colonization of toxigenic BI/NAP1/027 C. difficile in a mouse model. We found that B. thetaiotaomicron administration decreased the copies of C. difficile and inhibited inflammation in the colon. 16S rRNA sequencing showed that B. thetaiotaomicron administration was associated with a significantly increased relative abundance of Bacteroidetes and decreased level of Proteobacteria, leading to the reversal of the effect of antibiotics treatment and C. difficile infection on microbiota. B. thetaiotaomicron administration was associated with increases in the concentrations of alpha-muricholic acid, beta-muricholic acid, 12 ketolithocholic acid, and deoxycholic acid which are known to inhibit the growth of C. difficile, as well as reductions in the level of taurocholic acid, which promotes germination of C. difficile. Altered profile of major high abundance bile acids by B. thetaiotaomicron administration was similar to that with FMT treatment. Based on these results, we proposed the concept of ?the ratio of promotion/inhibition BAs? which would advance our understanding of the relation of C. difficile and BAs.

Automated summary

In this study, it was found that administration of Bacteroides thetaiotaomicron could reduce the colonization of toxigenic C. difficile in a mouse model, leading to decreased inflammation in the colon and favorable alterations in the gut microbiota composition. The administration of B. thetaiotaomicron also resulted in changes in bile acid profiles that are associated with inhibition of C. difficile growth, similar to the effects seen with fecal microbiota transplantation (FMT) treatment. This study proposed the concept of "the ratio of promotion/inhibition BAs" to further understand the relationship between C. difficile and bile acids.