Strain-Dependent Inhibition of Clostridioides Difficile by Commensal Carrying the Bile Acid-Inducible () Operon

is one of the leading causes of antibiotic-associated diarrhea. Gut microbiota-derived secondary bile acids and commensal that carry the bile acid-inducible () operon are associated with protection from infection (CDI), although the mechanism is not known. In this study, we hypothesized that commensal are important for providing colonization resistance against due to their ability to produce secondary bile acids, as well as potentially competing against for similar nutrients. To test this hypothesis, we examined the abilities of four commensal carrying the operon ( VPI 12708, ATCC 35704, , and ) to convert cholate (CA) to deoxycholate (DCA) and we determined whether the amount of DCA produced was sufficient to inhibit the growth of a clinically relevant strain. We also investigated the competitive relationships between these commensals and using an coculture system. We found that inhibition of growth by commensal supplemented with CA was strain dependent, correlated with the production of ∼2 mM DCA, and increased the expression of operon genes. We also found that was able to outcompete all four commensal in an coculture system. These studies are instrumental in understanding the relationship between commensal and in the gut, which is vital for designing targeted bacterial therapeutics. Future studies dissecting the regulation of the operon and and how this affects CDI will be important. Commensal carrying the operon, such as have been associated with protection against CDI; however, the mechanism for this protection is unknown. Herein, we show four commensal that carry the operon and affect growth in a strain-dependent manner, with and without the addition of cholate. Inhibition of by commensals correlated with the efficient conversion of cholate to deoxycholate, a secondary bile acid that inhibits germination, growth, and toxin production. Competition studies also revealed that was able to outcompete the commensals in an coculture system. These studies are instrumental in understanding the relationship between commensal and in the gut, which is vital for designing targeted bacterial therapeutics.