image: The current study is the first in the world to increase our knowledge of how the liver graft preservation method impacts fecal microbiota in the perioperative period of liver transplant patients. A highlight of this study, comparing SCS and NMP, is the 12-month follow-up to characterize how the gut microbiome responds longitudinally and correlates with fecal and breath organic compounds. A limitation of this study is that it is proof-of-concept with small group sizes of non-randomized cohorts, which limits statistical power. Additionally, many confounding variables limit the generalizability of these findings, including the lack of detailed information on diet, comorbidities, medications, and the fact that the majority of the study participants were White. Moreover, we were unable to categorize donor or recipient characteristics in the analysis due to limited case numbers, resulting in heterogeneity in donor and recipient distribution. However, our observation that fecal microbiota was impacted by the liver preservation method is novel and can help the transplantation community understand the benefits of NMP, which is increasingly used worldwide. Future research in larger randomized cohorts is warranted to determine whether the NMP-induced shift in gut microbiota composition and function impacts clinical outcomes and if breath VOCs could serve as biomarkers for the clinical course in liver transplant patients.
Credit: Gail A.M. Cresci, Qiang Liu
Background and Aims
End-stage liver disease is associated with disruptions in gut microbiota composition and function, which may facilitate gut-to-liver bacterial translocation, impacting liver graft integrity and clinical outcomes following liver transplantation. This study aimed to assess the impact of two liver graft preservation methods on fecal microbiota and changes in fecal and breath organic acids following liver transplantation.
Methods
This single-center, non-randomized prospective pilot study enrolled liver transplant patients whose grafts were preserved using either static cold storage or ex situ normothermic machine perfusion (NMP). Fresh stool and breath samples were collected immediately before surgery and at postoperative months 3, 6, and 12. Stool microbiota was profiled via 16S rRNA gene sequencing, stool short-chain fatty acids were measured using gas chromatography/-mass spectrometry, and breath volatile organic compounds (VOCs) were analyzed with selected-ion flow-tube mass spectrometry.
Results
Both cohorts experienced a loss of microbiota diversity and dominance by single taxa. The NMP cohort demonstrated enrichment of several beneficial gut taxa, while the static cold storage cohort showed depletion of such taxa. Various gut bacteria were found to correlate with stool short-chain fatty acids (e.g., lactic acid, butyric acid) and several VOCs.
Conclusions
Fecal microbiota alterations associated with end-stage liver disease do not fully normalize to a healthy control profile following liver transplantation. However, notable differences in microbiota composition and function were observed between liver graft preservation methods. Future research with larger randomized cohorts is needed to explore whether the NMP-associated shift in gut microbiota impacts clinical outcomes and if breath VOCs could serve as biomarkers of the clinical trajectory in liver transplant patients.
Full text
https://www.xiahepublishing.com/2310-8819/JCTH-2024-00352
The study was recently published in the Journal of Clinical and Translational Hepatology.
The Journal of Clinical and Translational Hepatology (JCTH) is owned by the Second Affiliated Hospital of Chongqing Medical University and published by XIA & HE Publishing Inc. JCTH publishes high quality, peer reviewed studies in the translational and clinical human health sciences of liver diseases. JCTH has established high standards for publication of original research, which are characterized by a study’s novelty, quality, and ethical conduct in the scientific process as well as in the communication of the research findings. Each issue includes articles by leading authorities on topics in hepatology that are germane to the most current challenges in the field. Special features include reports on the latest advances in drug development and technology that are relevant to liver diseases. Regular features of JCTH also include editorials, correspondences and invited commentaries on rapidly progressing areas in hepatology. All articles published by JCTH, both solicited and unsolicited, must pass our rigorous peer review process.
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Journal
Journal of Clinical and Translational Hepatology
Article Title
The Impact of Liver Graft Preservation Method on Longitudinal Gut Microbiome Changes Following Liver Transplant: A Proof-of-concept Study
Article Publication Date
22-Jan-2025