Metagenomes and Metatransciptomes from C. difficile infected murine cecal content

Clostridium difficile is the most common single cause of hospital-acquired infection over the last decade in the United States. Susceptibility is primarily associated with previous exposure to antibiotics, which compromise the structure and function of the gut bacterial community. While most antibiotics have been linked, specific classes correlate more strongly with recurrent or persistent C. difficile infection. In this study, we used a murine model of infection to explore the effect of distinct antibiotic classes on sustained C. difficile colonization, as well as the impact of infection on community-level gene expression and metabolism 18 hours post-infection. Utilizing metagenome-enable metatranscriptomics, supplemented by untargeted metabolomic analysis, we found that C. difficile infection has differentially larger impacts on the metabolic activity of the microbiota across multiple antibiotics that allow for persistent colonization. These differences were enriched in pathways associated with amino acid metabolism and particularly in non-dominant species. Conversely, in clindamycin pretreatment where C. difficile is cleared within 8 days, the effect of infection on the microbiota is only detectable in community structure but not in activity. Our results suggest that C. difficile is able to restructure the nutrient-niche landscape in certain gut environments in order to promote persistent infection.