Secretome Suppresses Virulence Gene Expression of in a Bile Acid-independent Manner

infection (CDI) is a major health concern and one of the leading causes of hospital-acquired diarrhea in many countries. infection is challenging to treat as is resistant to multiple antibiotics. Alternative solutions are needed as conventional treatment with broad-spectrum antibiotics often leads to recurrent CDI. Recent studies have shown that specific microbiota-based therapeutics such as bile acids (BAs) are promising approaches to treat CDI. encodes the bile acid-induced () operon that carries out 7-alpha-dehydroxylation of liver-derived primary BAs to secondary BAs. This biotransformation is thought to increase the antibacterial effects of BAs on . Here, we used an automated multistage fermentor to study the antibacterial actions of and BAs on in the presence/absence of a gut microbial community derived from healthy human donor fecal microbiota. We observed that inhibited growth when the medium was supplemented with primary BAs. Transcriptomic analysis indicated upregulation of operon and suppressed expression of exotoxins that mediate CDI. We also observed BA-independent antibacterial activity of the secretome from s cultured overnight in a medium without supplementary primary BAs, which suppressed growth and exotoxin expression in mono-culture. Further investigation of the molecular basis of our observation could lead to a more specific treatment for CDI than current approaches. IMPORTANCE There is an urgent need for new approaches to replace the available treatment options against infection (CDI). Our novel work reports a bile acid-independent reduction of growth and virulence gene expression by the secretome of . This potential treatment combined with other antimicrobial strategies could facilitate the development of alternative therapies in anticipation of CDI and in turn reduce the risk of antimicrobial resistance.