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Metagenomic next-generation sequencing of matched donor–recipient pairs reveals pathogen transmission dynamics and informs antimicrobial therapy in liver transplantation: a retrospective cohort study

Year: 2026

Type: article

Abstract: Background Post-transplant infections remain a leading cause of morbidity and mortality after liver transplantation (LT). Conventional microbiological culture has well-recognized limitations in sensitivity and pathogen spectrum coverage. Metagenomic next-generation sequencing (mNGS) has emerged as a promising diagnostic platform. However, its systematic evaluation across matched donor–recipient pairs, including characterization of possible donor-to-recipient pathogen transmission and its impact on antimicrobial stewardship, remains limited. Methods We retrospectively enrolled 45 consecutive LT donor–recipient pairs. Multiple sample types were collected from donors ( n = 124) and recipients ( n = 97) and subjected to both mNGS and conventional culture. Recipients were stratified into infection ( n = 29) and non-infection ( n = 16) groups. Pathogen detection rates, diagnostic performance metrics, donor-to-recipient transmission events, and mNGS-informed antimicrobial modifications were systematically analyzed. Results Post-transplant infection occurred in 64.4% of recipients, predominantly involving the pulmonary compartment (89.7%). mNGS achieved significantly higher overall positivity rates than culture in both donors (95.6% vs . 80.0%) and recipients (64.4% vs . 22.2%), with superior detection of fungi and exclusive identification of all viral pathogens. The pathogen-level concordance between methods was predominantly partial (75%–78%). At the patient level, mNGS demonstrated a sensitivity of 69.0% versus 31.0% for culture, while culture maintained higher specificity (93.8% vs . 43.8%). A diverse pathogen landscape was identified, including Pneumocystis jirovecii , rare molds, cytomegalovirus (CMV), and Epstein–Barr virus (EBV)—all exclusively detected by mNGS. A total of 11 possible donor-to-recipient transmission events involving six pathogens were identified across 11 pairs, and 54.5% of affected recipients developed clinical infections, with Klebsiella pneumoniae accounting for the majority of transmission events. mNGS results informed antimicrobial treatment modifications in 69.0% of infected recipients. In the univariate analysis, liver cancer showed an exploratory association with lower post-transplant infection risk (OR = 0.10, 95%CI = 0.02–0.46, p = 0.003). Conclusions This retrospective matched-pair study suggests that mNGS substantially expands pathogen detection beyond conventional culture, enabling the identification of clinically relevant possible donor-derived pathogen transmission and informing antimicrobial treatment modifications in the majority of infected recipients. These findings support mNGS as an adjunctive peri-transplant diagnostic tool pending prospective multicenter validation.

Source: Frontiers in Cellular and Infection Microbiology

DOI: 10.3389/fcimb.2026.1919428