Contribution of inhibitory metabolites and competition for nutrients to colonization resistance against clostridioides difficile by commensal clostridium

Abstract

Clostridioides difficile is an anaerobic pathogen that causes significant morbidity and mor-tality. Understanding the mechanisms of colonization resistance against C. difficile is important for elucidating the mechanisms by which C. difficile is able to colonize the gut after antibiotics. Commensal Clostridium play a key role in colonization resistance. They are able to modify bile acids which alter the C. difficile life cycle. Commensal Clostridium also produce other inhibitory metabolites including antimicrobials and short chain fatty acids. They also compete with C. difficile for vital nutrients such as proline. Understanding the mechanistic effects that these metabolites have on C. difficile and other gut pathogens is important for the development of new therapeutics against C. difficile infection (CDI), which are urgently needed.