Metatranscriptome of murine cecal community following antibiotic pretreatment and C. difficile infection. Transcriptome. Cecal microbiome

Clostridium difficile has become 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. Furthermore, specific classes correlate more strongly with recurrent or persistent C. difficile infection. 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 untargeted metabolomic analysis, we found that C. difficile infection has larger impacts on the metabolic activity of the microbiota across cefoperazone and streptomycin-treated mice, which become persistently colonized. Using metagenome-enabled metatranscriptomics, we observed that the infected communities were enriched in pathways associated with amino acid metabolism and particularly in non-dominant species relative to mock-infected controls. Conversely, in clindamycin pretreatment where C. difficile is cleared within 8 days, the effect of infection on the microbiota was only detectable in changes to the community structure but not in metabolic activity or gene expression. Our results suggest that C. difficile is able to restructure the nutrient-niche landscape in certain gut environments in order to promote persistent infection.