Microbiota Accessible Carbohydrates Suppress Clostridium difficile in a Murine Model

Clostridium difficile ( Cd ) is an opportunistic diarrheal pathogen and Cd infection (CDI) represents a major healthcare concern, causing an estimated 15,000 deaths per year in the United States alone. Several enteric pathogens, including Cd , leverage inflammation and the accompanying microbial dysbiosis to thrive in the distal gut. Although diet is among the most powerful available tools for affecting the health of humans and their relationship with their microbiota, investigation into the effects of diet on CDI has been limited. Here, we show in mice that the consumption of microbiota accessible carbohydrates (MACs) found in dietary plant polysaccharides has a significant impact on CDI. Specifically, using a murine model of antibiotic-induced CDI that typically resolves within 12 days of infection, we demonstrate that MAC-deficient diets perpetuate CDI. We show that Cd can be cleared through the addition of either a diet containing a complex mixture of MACs or a simplified diet containing inulin as the sole MAC source. We show that switches between these dietary conditions are coincident with changes to microbiota membership, its metabolic output and Cd -mediated inflammation. Together, our data demonstrate the outgrowth of MAC-utilizing taxa and the associated end products of MAC metabolism, namely the short chain fatty acids (SCFAs) acetate, propionate, and butyrate, are associated with decreased Cd fitness despite increased toxin production in the gut. Our findings, when placed into the context of the known fiber deficiencies of a human Western diet, suggest utility in microbiota-informed MAC-centric dietary strategies for the mitigation of CDI and other gastrointestinal infectious diseases.