PRJNA427597
Clostridium Difficile 16S and ITS Matched Investigation
Clostridium difficile infection (CDI) is the most common nosocomial infection in the United States, being associated with high recurrence and persistence rates. Though the relationship between intestinal dysbiosis and CDI is well-known, it is unclear whether different forms of dysbiosis may potentially affect the course of CDI. How this is further influenced by difficile-directed antibiotics is virtually uninvestigated. In this study, diarrheal stool samples were collected from 20 hospitalized patients, half of whom were confirmed to have CDI. Analyzing tissue ex vivo and in duplicate, CDI and non-CDI fecal samples (n=176) were either antibiotic untreated or were treated with metronidazole, vancomycin or fidaxomicin, the three most common CDI therapies. Evaluation of the microbial community composition, interactions, and predicted metabolic functions was assessed using 16S rRNA gene and ITS sequencing, bipartite network analysis and PICRUSt. Our results demonstrate that while all difficile-directed antibiotics were associated with similar reductions in alpha diversity, beta-diversity significantly differed based on the particular antibiotic, with differentiating relative abundances of bacterial and fungal assemblages. With the exception of fidaxomicin, each antibiotic was associated with the emergence of potentially pathogenic fungal OTUs, with predicted bacterial functions enriched for xenobiotic metabolism which could perpetuate the dysbiosis driving CDI. Toxin- independent mechanisms of colitis related to the relative abundance of pathogenic bacteria and fungi were also noted. This study suggests that a transkingdom interaction between fungi and bacteria may be important in CDI pathophysiology, including being a factor in the historically high persistence and recurrence rates associated with this disease.