Association between salivary microbiota-related amino acid metabolic dysregulation and tacrolimus-induced gingival overgrowth following kidney transplantation.

BACKGROUND

Kidney transplant (KT) recipients require lifelong immunosuppressive therapy to prevent allograft rejection. Drug-induced gingival overgrowth (DIGO) is a notable adverse effect of tacrolimus, for which effective preventive or therapeutic strategies are lacking. Dysbiosis of the oral microbiota has been implicated as a major risk factor for DIGO. However, its mechanistic role remains poorly understood.

RESULTS

Twenty KT recipients with newly diagnosed DIGO while receiving tacrolimus were enrolled, along with 20 matched controls with stable graft function. Salivary samples were collected and subjected to metagenomic and untargeted metabolomic profiling. Taxonomic analysis revealed greater microbial heterogeneity in DIGO patients compared to more interconnected communities observed in controls. Periodontitis-associated taxon, including Porphyromonas gingivalis, were enriched in the DIGO group. Multiple differentially expressed microbial genes and metabolites were identified, predominantly enriched in disordered amino acid metabolic pathways. Key metabolites-such as L-proline, carnosine, choline, 5-aminolevulinic acid, and spermidine-showed strong associations with DIGO-related taxon.

CONCLUSION

A strong association was observed between salivary microbial composition, metabolic profiles, and DIGO. The identified microbiota and metabolite alterations suggest a potential link between amino acid metabolic dysregulation and gingival fibroblast-related pathways in DIGO. These findings provide new insights into the biological features of DIGO and offer a foundation for future mechanistic and therapeutic studies.