Fecal microbiome alterations of mice following immunization with gold nanoparticle vaccines against enterohemorrhagic Escherichia coli.

Background: Enterohemorrhagic Escherichia coli (EHEC), a group of enteric pathogenic bacteria that is a major cause of human diarrheal disease, must interact with the diverse intestinal microbiome during colonization and subsequently overcome the environmental challenges to survive and cause disease. While this relationship, and how the microbiome modulates infection of EHEC, has been studied, it is less understood how the microbiome is impacted during treatment for an EHEC infection. One area that is notably lacking in knowledge is how vaccination can impact the intestinal microbiome composition, and therefore, influence vaccine efficacy. We previously developed vaccine formulations consisting of gold nanoparticles (AuNPs) conjugated to various EHEC antigens and tested them in mice models using both EHEC and its murine counterpart Citrobacter rodentium. The goal of this study was to evaluate the relationship between these EHEC vaccines and their effects on the gut microbiome.

Results: We found that immunization with the vaccines or adjuvant-only control did not lead to major alterations in the composition of the fecal microbiome; however, there were measurable variations in individual mice within the same vaccine group housed in separate cages. Also, immunization with one vaccine (AuNP-EscC) prevented both a decrease in the diversity of the fecal microbiome and an increase in detectable C. rodentium following infection compared to control animals.

Conclusions: Overall, our small study argues in favor of evaluating the intestinal microbiome during vaccine development not just for EHEC, but for other enteric pathogens.