In vivo commensal control of Clostridioides difficile virulence.

Leveraging systems biology approaches, we illustrate how metabolically distinct species of Clostridia protect against or worsen Clostridioides difficile infection in mice by modulating the pathogen's colonization, growth, and virulence to impact host survival. Gnotobiotic mice colonized with the amino acid fermenter Paraclostridium bifermentans survive infection with reduced disease severity, while mice colonized with the butyrate-producer, Clostridium sardiniense, succumb more rapidly. Systematic in vivo analyses revealed how each commensal alters the gut-nutrient environment to modulate the pathogen's metabolism, gene regulatory networks, and toxin production.

Genomic Determination of Relative Risks for Clostridioides difficile Infection From Asymptomatic Carriage in Intensive Care Unit Patients.

Background: Clostridioides difficile infections (CDIs) are among the most prevalent hospital-associated infections (HAIs), particularly for intensive care unit (ICU) patients. The risks for developing active CDI from asymptomatic carriage of C. difficile are not well understood.