Multi-omic profiling a defined bacterial consortium for treatment of recurrent Clostridioides difficile infection.

Donor-derived fecal microbiota treatments are efficacious in preventing recurrent Clostridioides difficile infection (rCDI), but they have inherently variable quality attributes, are difficult to scale and harbor the risk of pathogen transfer. In contrast, VE303 is a defined consortium of eight purified, clonal bacterial strains developed for prevention of rCDI. In the phase 2 CONSORTIUM study, high-dose VE303 was well tolerated and reduced the odds of rCDI by more than 80% compared to placebo. VE303 organisms robustly colonized the gut in the high-dose group and were among the top taxa associated with non-recurrence. Multi-omic modeling identified antibiotic history, baseline stool metabolites and serum cytokines as predictors of both on-study CDI recurrence and VE303 colonization. VE303 potentiated early recovery of the host microbiome and metabolites with increases in short-chain fatty acids, secondary bile acids and bile salt hydrolase genes after antibiotic treatment for CDI, which is considered important to prevent CDI recurrences. These results support the idea that VE303 promotes efficacy in rCDI through multiple mechanisms.