Transplantation-associated long-term immunosuppression promotes oral colonization by potentially opportunistic pathogens without impacting other members of the salivary bacteriome
Solid-organ transplant recipients rely on pharmacological immunosuppression to prevent allograft rejection. The effect of such chronic immunosuppression on the microflora at mucosal surfaces is not known. We evaluated the salivary bacterial microbiome of 20 transplant recipients and 19 non-immunosuppressed controls via 454-pyrosequencing of 16S rRNA gene amplicons. Alpha-diversity and global community structure did not differ between transplant and control subjects. However, principal coordinate analysis showed differences in community membership. Taxa more prevalent in transplant subjects included operational taxonomic units (OTUs) of potentially opportunistic Gammaproteobacteria such as Klebsiella pneumoniae, Pseudomonas fluorescens, Acinetobacter sp., Vibrio spp., Enterobacteriaceae sp. and the genera Acinetobacter and Klebsiella. Transplant subjects had increased proportions of Pseudomonas aeruginosa, Acinetobacter sp., Enterobacteriaceae sp. and Enterococcus faecalis, among other OTUs, while increased genera included Klebsiella, Acinetobacter, Staphylococcus and Enterococcus. Furthermore, in transplant subjects, the dose of the immunosuppressant prednisone positively correlated with bacterial richness, while prednisone and mycophenolate mofetil doses positively correlated with the prevalence and proportions of transplant-associated taxa. Correlation network analysis of OTU relative abundance revealed a cluster containing potentially opportunistic pathogens as transplant-associated. This cluster positively correlated with serum levels of C-reactive protein, suggesting a link between the resident flora at mucosal compartments and systemic inflammation. Network connectivity analysis revealed opportunistic pathogens as highly connected to each other and to common oral commensals, pointing to bacterial interactions that may influence colonization. This work demonstrates that immunosuppression aimed at limiting T-cell-mediated responses creates a more permissive oral environment for potentially opportunistic pathogens without affecting other members of the salivary bacteriome.