Dietary Fiber Modulates the Window of Susceptibility to Clostridioides difficile Infection

Area of Science:

• Microbiology and Immunology
• Gastroenterology
• Nutritional Science

Background:

• Clostridioides difficile infection (CDI) epidemiology is evolving, necessitating a deeper understanding of infection risk factors.
• Antibiotic use disrupts the gut microbiome, increasing susceptibility to opportunistic pathogens like C. difficile.
• Previous observations suggested a potential role for dietary fiber in modulating C. difficile susceptibility.

Purpose of the Study:

• To investigate the hypothesis that dietary fiber modulates susceptibility to C. difficile infection (CDI) following antibiotic exposure.
• To examine the impact of fiber on bile acid and microbiota composition, key factors in colonization resistance.
• To directly assess the effect of a fiber-free diet on CDI susceptibility in a murine model.

Main Methods:

• Analyzed bile acid and microbiota composition in human subjects on a low-fiber diet.
• Utilized a murine model to test the impact of fiber-rich versus fiber-free diets on CDI susceptibility post-antibiotic treatment.
• Quantified CDI susceptibility and characterized alterations in bile acid and microbiota profiles in the animal model.

Main Results:

• A low-fiber diet in humans correlated with increased fecal primary conjugated bile acids, including taurocholic acid, which promotes C. difficile colonization.
• Mice on a fiber-free diet exhibited prolonged and increased susceptibility to CDI, linked to significant bile acid alterations.
• Fiber-free diet induced long-lasting perturbations in the gut microbiota, notably depleting commensals crucial for colonization resistance against C. difficile.

Conclusions:

• Reduced dietary fiber intake post-antibiotic use prolongs susceptibility to CDI by disrupting gut microbiota and bile acid homeostasis.
• Diet represents a critical and modifiable risk factor influencing CDI susceptibility, particularly in the context of antibiotic therapy.
• Findings underscore the importance of dietary interventions in preventing and managing C. difficile infections.