Dietary Fiber Modulates the Window of Susceptibility to Clostridioides difficile Infection.

Abstract

Clostridioides difficile epidemiology is rapidly evolving, and understanding the factors that contribute to one's risk of C difficile infection (CDI) is urgently needed. Based on our observations in a dietary intervention study, we hypothesized that fiber modulates susceptibility to C difficile after antibiotic exposure and investigated this using human specimens and murine models. To determine whether fiber impacts factors known to mediate colonization resistance against C difficile, we investigated bile acid and microbiota composition in human subjects consuming a low-fiber diet. To directly test the impact of a fiber-free diet on CDI susceptibility, we treated mice with fiber-rich or fiber-free diets and quantified CDI susceptibility after antibiotic use as well as characterized alterations in bile acid and microbiota composition. A low-fiber diet leads to increased fecal primary conjugated bile acids in humans, including bile acids known to promote C difficile colonization such as taurocholic acid. Using a novel mouse model of CDI, we show that a fiber-free diet leads to prolonged and increased susceptibility to CDI that is associated with alterations in bile acids. We further report long-lasting perturbation to the microbiota, highlighted by depletion of commensals known to promote colonization resistance against C difficile. Consumption of a low-fiber diet after antibiotic use contributes to a prolonged susceptibility to CDI that corresponds to a perturbation in both microbiota and bile acid composition. These results suggest that in the context of antibiotic treatment, diet is a critical, modifiable risk factor for CDI susceptibility.