Dietary fiber modulates the window of susceptibility to Clostridioides difficile infection

Abstract

Background & Aims

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 post-antibiotic exposure and investigated this using human specimens and murine models.

Methods

To determine whether fiber impacts factors known to mediate colonization resistance against C. difficile, we investigated bile acid and microbiota composition in human subjects on 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 both bile acid and microbiota composition.

Results

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 (TCA). 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.

Conclusions

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.