Objective
To determine the therapeutic effects of dietary supplementation on C. difficile infection (CDI).
Background
With limited treatment options, the rise of Clostridium difficile-associated disease has spurred on the search for novel therapies. Recent data define a role for the aryl hydrocarbon receptor (AHR) and diet-derived AHR ligands in mucosal immunity. We investigated the efficacy of indole-3-carbinol (I3C), a dietary supplement and AHR precursor ligand, in a murine model of CDI.
Methods
C57BL/6 (B6), AHR−/− and AHR+/− mice were placed on either grain-based or semi-purified diets with or without I3C prior to and during CDI. Mice were followed clinically for a minimum of 6 days, or euthanized between days 0 and 4 of inoculation for analysis of the inflammatory response and microbiota.
Results
B6 mice fed an AHR ligand-deficient, semi-purified diet have significantly increased disease severity (p < 0.001) and mortality (p<0.001) compared to mice fed diet containing I3C. The addition of I3C to the diet of AHR null mice had less of an impact than in AHR heterozygous littermates, although some protection was seen. Mice on semi-purified I3C-diet had increased cecal Tregs, ILC3s, and γδ T cells as well as an increased neutrophilic response without increased inflammation or bacterial translocation compared to controls.
Conclusions
I3C is a powerful treatment to reduce impact of CDI in mice. The findings indicate I3C may be acting through both AHR-dependent and -independent mechanisms in this model. Dietary supplementation with I3C is a potential new therapy for prevention and amelioration of C. difficile disease.