Related Experiment Video
Updated: Sep 17, 2025
Murine Fecal Isolation and Microbiota Transplantation
Published on: May 26, 2023
Short-term and long-term development of gut microbiota in children after liver transplantation-A prospective
Imeke Goldschmidt1,2, Miriam Kramer1,3,4, Norman Junge1,5
1Division of Pediatric Hepatology and Liver Transplantation, Department of Pediatric Liver, Kidney and Metabolic Diseases and Neuropediatrics, Hannover Medical School, Hannover, Germany.
Insights
Pediatric liver disease alters gut microbiota (GM). Pediatric liver transplantation (pLT) impacts GM, with dysbiosis persisting post-transplant, affecting graft health.
Area of Science:
- Microbiology
- Gastroenterology
- Pediatric Surgery
Background:
- Gut microbiota (GM) in pediatric end-stage liver disease and post-pediatric liver transplantation (pLT) is poorly understood.
- GM alterations may impact graft function and patient outcomes after pLT.
Purpose of the Study:
- To analyze GM composition and function in children before and after pLT.
- To assess the impact of disease severity, treatment, and pLT on GM.
- To correlate GM with graft and patient health post-pLT.
Main Methods:
- Quantitative 16S rRNA gene analyses and shotgun metagenomics on fecal samples.
- Comparison of pre-pLT patients, post-pLT patients (longitudinal), long-term survivors (LT-pLT), and healthy controls (HCs).
- Random Forest analysis to predict hepatocellular damage.
Main Results:
- Pre-pLT patients exhibited reduced GM alpha-diversity and altered composition linked to disease severity and rifampicin treatment.
- Dysbiosis worsened post-pLT, with partial recovery by 3 months, but GM levels remained below HCs.
- Reduced GM diversity and function correlated negatively with transaminase levels; GM predicted hepatocellular damage with high accuracy (AUC: 0.89).
Conclusions:
- Comprehensive, quantitative insights into pediatric GM before and after pLT were provided.
- A significant link between GM alterations and long-term graft health was identified.
- Modulating GM function presents potential therapeutic targets for improving graft and patient health.
Abstract:
In children, little is known about gut microbiota (GM) in end-stage liver disease and its association with graft function after pediatric liver transplantation (pLT). We analyzed GM composition and function in children before pLT, longitudinally post-pLT and in long-term survivors (LT-pLT) in order to assess the impact of disease severity, treatment, and pLT on GM and delineate associations with graft and patient health. Fecal samples (FS) of 29 children [17f (female), age 2.6 (0.2-15.7) years] awaiting pLT were included with longitudinal follow-ups until 12 months post-transplant in 18, and compared with 38 LT-pLT [21f, age 11 (2.7-17.7) years, 7.8 (1.0-17.0) years post-pLT] and 94 healthy controls (HCs). Samples were analyzed using quantitative 16S rRNA gene analyses combined with shotgun metagenomics (subset of samples). Pre-pLT patients showed reduced alpha-diversities and altered GM composition compared with LT-pLT and HC, associated with disease severity and anti-pruritic treatment with rifampicin. Dysbiosis increased after pLT and started to recover after 3M (months). Although bacterial concentrations, alpha diversity, and gene richness increased post-pLT, levels remained below those of HC. Abundances of key functions, for example, the capacity to synthesize butyrate, also remained reduced. Quantitative analyses revealed the true extent of differences between patients and HC that were underestimated using relative abundance data. GM diversity and functional capacities correlated negatively with transaminase levels mid-term and long-term after pLT. Random Forest analyses based on GM were able to predict hepatocellular damage at high accuracy (AUC: 0.89). We provide comprehensive, quantitative insights into GM composition and function before and after pLT. A link between GM alterations and (long-term) graft health was uncovered, providing possible targets to modulate GM function in order to increase graft and patient health.
