Mathematical Modeling of the Effects of Nutrient Competition and Bile Acid Metabolism by the Gut Microbiota on Colonization Resistance Against Clostridium difficile

Clostridium difficile is the leading cause of infectious diarrhea in hospitals and one of the most common healthcare associated infections. Antibiotics alter the normal gut microbiota and facilitate the colonization of enteric pathogens such as C. difficile. Our objective is to elucidate the role of bile acids and other mechanisms in providing colonization resistance against C. difficile. We formulated and analyzed differential equation models for microbial interactions in the gut and bile acid dynamics, as well as a combined model including both mechanisms. Our analysis indicates that bile acids do not prevent C. difficile colonization, but they regulate the onset of C. difficile colonization and growth after antibiotic perturbation. These results have implications in the development of novel ways to inhibit C. difficile infection.