Abstract
BACKGROUND: Immunosuppression during liver transplantation (LT) enables the prevention and treatment of organ rejection, but poses a risk for severe infectious diseases. Antimicrobials are often required for patients after LT. Recently, the genomes of multiple microorganisms have been detected in blood, which is essentially sterile. Immune modulation and antimicrobials affect the blood microbiome. Thus, determining the impact of immunosuppression and antimicrobials on the microbiome may be important to understand immunocompetence, predict clinical adverse events after LT such as acute cellular rejection (ACR), and treat infectious diseases. METHODS: Fifty-one patients who received LT at Nagoya University Hospital from 2016 to 2018 were enrolled. Plasma samples were retrospectively collected within a week after LT, 4±1 weeks after LT, 8±1 weeks after LT, and within 2 days after a positive blood culture. A total of 111 plasma samples were analyzed using shotgun next-generation sequencing (NGS). Sequence data were imported into the custom-made analysis pipeline PATHDET. RESULTS: The relative abundance of Anelloviridae, Nocardiaceae, Microbacteriaceae, and Enterobacteriaceae significantly changed during the postoperative period (figure 1). Microbiome diversity was higher within a week after LT than at 8 weeks after LT. Antimicrobials were significantly associated with the microbiome of LT recipients. In addition, the proportion of Enterobacteriaceae was significantly decreased (figure 2) and the plasma microbiome diversity was significantly higher in patients with ACR than in non-ACR patients. Finally, sequencing reads of bacteria isolated from blood cultures were predominantly identified by NGS in 8 of 16 samples (figure 3), and human herpesvirus 6 was detected as a causative pathogen in one recipient with severe infectious diseases. Change in the relative abundance of each microorganism at the family level of taxonomic hierarchy in plasma samples after liver transplantation Comparison of the plasma microbiome at the family level in patients with and without acute cellular rejection Relative abundance of microorganisms at the species level in plasma from patients with positive blood cultures CONCLUSION: The metagenomic NGS technique has great potential in revealing the plasma microbiome and is useful as a comprehensive diagnostic procedure in clinical settings. Temporal dynamics of specific microorganisms may be used as indirect markers for the determination of immunocompetence and ACR in LT recipients. DISCLOSURES: All Authors: No reported disclosures