Pretransplant Gut Microbiome Signatures Predict Early Acute Rejection After Kidney Transplantation

Area of Science:

• Immunology
• Microbiology
• Transplantation Science

Background:

• Early detection of kidney transplant rejection is crucial to prevent irreversible allograft damage.
• Conventional methods often identify rejection only after significant injury has occurred.
• The gut microbiome's role in immune homeostasis suggests its potential for predicting transplant outcomes.

Purpose of the Study:

• To investigate whether pre-transplant gut microbiome composition and function can predict early acute kidney transplant rejection.
• To identify specific microbial taxa and genes associated with rejection.
• To develop and validate microbiome-augmented predictive models.

Main Methods:

• Shotgun metagenomic sequencing of pre-transplant stool samples from 78 kidney transplant recipients.
• Comparison of microbiome composition, functional profiles, and networks between rejection and non-rejection groups.
• Development and testing of stepwise Random Forest models, including subgroup analyses and temporal validation.

Main Results:

• Reduced abundance of Phascolarctobacterium faecium and a key propionate-biosynthetic enzyme (mcmB) were significantly associated with early acute rejection.
• Microbiome network analysis revealed distinct reorganization patterns in rejection cases.
• Microbiome-augmented models demonstrated improved predictive accuracy (AUC up to 0.765) and outperformed clinical-only models, with validation in a temporal cohort.

Conclusions:

• Pre-transplant gut microbiome signatures are independently associated with early acute kidney transplant rejection.
• Integrating microbiome data into predictive models enhances risk stratification capabilities.
• These findings support the use of microbiome analysis for pre-transplant risk assessment in kidney transplantation.