Intestinal microbiome and acute transplanted kidney rejection – results of a single-center, case-control study

Kidney transplantation (KTx) is the preferred form of renal replacement therapy. Acute rejection of the transplanted kidney (AR) may impair long-term outcomes. The gut microbiota influences immune system activity; however, its relationship with AR remains underexplored. This study aimed to investigate the relationship between the gut microbiome and risk of AR shortly after KTx. In this single-center, retrospective case-control study, 10 patients with consecutive biopsy-proven AR shortly after KTx (median age 43 (38, 48) years) were matched by sex and age with 20 patients without AR (median age 42 (37, 48) years) during a one-year follow-up after KTx. Stool samples were collected 4–7 days after KTx for microbiome analysis using Illumina shallow shotgun sequencing. Bioinformatics analysis included taxonomic and functional profiling, with predictive modeling performed using a random forest model (RF). Model performance was evaluated using receiver operating characteristic (ROC) curves and the area under the curve (AUC). No significant differences in gut microbiota diversity were observed between the groups. The differential abundance analysis did not identify any taxonomic features that remained significant after adjusting for possible covariates. The predictive RF models varied in performance, with functional KEGG pathway profiles showing the highest predictive value (AUC = 0.73). Key metabolic pathways implicated in such profiles included lipid metabolism, glycan biosynthesis and metabolism, and terpenoid and polyketide metabolism. No universal taxonomic gut microbiota markers for AR have been identified. The functional profile of the gut microbiome may be related to AR with specific metabolic pathways potentially involved in the underlying mechanisms. These findings suggest a role of immunomodulation, inflammation, and metabolic regulation in AR.