Clostridium scindens secretome suppresses virulence gene expression of Clostridioides difficile in a bile-acid-independent manner

We used an automated multistage fermentor to study the antibacterial actions of Clostridium scindens and bile acids (BAs) on Clostridioides difficile in the presence/absence of a gut microbial community derived from healthy human donor fecal microbiota. We observed that C. scindens inhibited C. difficile growth when the medium was supplemented with primary BAs. Transcriptomic analysis indicated upregulation of C. scindens bai operon and suppressed expression of C. difficile exotoxins that mediate CDI. We also observed BA-independent antibacterial activity of the secretome from C. scindens cultured overnight in a medium without supplementary primary BAs, which suppressed growth and exotoxin expression in C. difficile mono-culture. Further investigation of the molecular basis of our observation could lead to a more specific treatment for CDI than current approaches.