The evaluation of fecal microbiota transplantation vs vancomycin in a Clostridioides difficile infection model

Abstract

Vancomycin is the preferred treatment for Clostridioides difficile infection (CDI) but has been associated with a high recurrence rate of CDI in treated patients. Fecal microbiota transplantation (FMT) has emerged as a remarkably successful treatment for recurrent CDI (rCDI). Herein, we present a mouse model of CDI to further define the changes in intestinal inflammation, flora, and metabolites following FMT versus vancomycin treatment and to find the potential therapy to restore colonization resistance. Both FMT and vancomycin treatment could ameliorate CDI-induced clinical features and intestinal tissue damage, with decrease in the levels of inflammatory mediators like IL-1β, IL-6, TNF-α, G-CSF, and MCP-1 in the colon and plasma. Observing the fecal gut microbiome profile revealed that unlike vancomycin, FMT could replenish intestinal microbiota by augmenting the relative abundance of the phylum Bacteroidetes and eliminating the abundance of the phylum Proteobacteria. FMT also reduced the levels of several carbohydrates, such as raffinose and fructose-6-phosphate, and amino acids, including tryptophan and glutamyl-valine, in the gut metabolome, thus suppressing C. difficile germination and growth. Our results suggest that the FMT-induced reconstruction of a specific gut community structure and restoration of metabolites promote the recovery of colonization resistance in mice better than vancomycin, thus offering new insights for the prevention of rCDI. KEY POINTS: • Both FMT and vancomycin ameliorate CDI-induced inflammatory response. • FMT restores a specific community structure and gut metabolites. • Mice treated with FMT may promote the recovery of colonization resistance and has a better outcome.

Keywords: Clostridioides difficile; Fecal microbiota transplantation; Metabolome; Microbiota; Vancomycin.