Abstract
Clostridioides difficile infection (CDI) is a major health concern and one of the leading causes of hospital-acquired diarrhea in many countries. C. difficile infection is challenging to treat as C. difficile
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. Clostridium scindens encodes the bile acid-induced (bai)
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 C. difficile. Here, we used an automated multistage fermentor to study the antibacterial actions of C. scindens and BAs on C. 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.
Original language | English |
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Article number | e03933-22 |
Journal | Microbiology Spectrum |
Volume | 11 |
Issue number | 5 |
Number of pages | 18 |
ISSN | 2165-0497 |
DOIs | |
Publication status | Published - 2023 |
Keywords
- Clostridioides difficile infection
- Clostridium scindens
- Bile acids
- Secretome
- Human Intestinal Microbial Ecosystem
- Gut microbiome
- Oomics data
- Pathogen
- Toxin suppression