Metagenomic next-generation sequencing of matched donor–recipient pairs reveals pathogen transmission dynamics and informs antimicrobial therapy in liver transplantation: a retrospective cohort study
- 1Organ Transplantation Center, The Affiliated Hospital of Qingdao University , , ,
- 2WillingMed Technology (Beijing) Co., Ltd , ,
- 3Department of Orthopaedics, The Affiliated Hospital of Qingdao University , , ,
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.
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BibTeX
@article{feng2026metagenomic,
title = {{Metagenomic next-generation sequencing of matched donor–recipient pairs reveals pathogen transmission dynamics and informs antimicrobial therapy in liver transplantation: a retrospective cohort study}},
author = {Shuai Feng and Jinquan Liu and Xiaojing Zhang and Lianghao Zhang and Shengbao Zhao and Nannan Jiang and Jinzhen Cai and Yafeng Zheng and Wei Gai and Chuanshen Xu},
journal = {Frontiers in cellular and infection microbiology},
year = {2026},
month = oct,
doi = {10.3389/fcimb.2026.1919428},
url = {https://europepmc.org/article/PMC/PMC13724449},
note = {CC BY},
}
RIS
TY - JOUR
TI - Metagenomic next-generation sequencing of matched donor–recipient pairs reveals pathogen transmission dynamics and informs antimicrobial therapy in liver transplantation: a retrospective cohort study
AU - Shuai Feng
AU - Jinquan Liu
AU - Xiaojing Zhang
AU - Lianghao Zhang
AU - Shengbao Zhao
AU - Nannan Jiang
AU - Jinzhen Cai
AU - Yafeng Zheng
AU - Wei Gai
AU - Chuanshen Xu
PY - 2026
DA - 2026/10/19
JO - Frontiers in cellular and infection microbiology
DO - 10.3389/fcimb.2026.1919428
UR - https://europepmc.org/article/PMC/PMC13724449
AB - 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.
SN - 2235-2988
ER -