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Abstract: FR-PO771

The Role of Gut Microbiome in Dose Selection of Envarsus Among High Tacrolimus Metabolizers

Session Information

Category: Transplantation

  • 2002 Transplantation: Clinical

Authors

  • Melancon, Joseph Keith, The George Washington University, Washington, District of Columbia, United States
  • Nayebpour, Mehdi, Virginia BioAnalytics, Washington, District of Columbia, United States
  • Ekwenna, Obi Davis, The University of Toledo, Toledo, Ohio, United States
  • Ibrahim, Hanaa, The George Washington University, Washington, District of Columbia, United States
  • Koizumi, Naoru, The George Washington University, Washington, District of Columbia, United States
Background

The role of gut microbiome in kidney transplant outcomes has been of great interest among researchers and physicians. Yet the number of studies to investigate the effect of microbiome on kidney transplant has been limited, particularly in regard to personalized medicine. Preliminary studies show significant associations between the relative abundance of certain bacterial species such as Faecalibacterium prausnitzii and tacrolimus (Tac) dosing. No study has translated the findings into application. This study develops a dose selection algorithm based on gut microbiome and gene marker profile of kidney transplant patients.

Methods

30 kidney transplant patients from the George Washington University Hospital and the University of Toledo Medical Center were recruited. From each subject 3 ml of blood was collected for gene marker sequencing of CYP3A5. 2 stool samples were collected per subject for gut microbiome sequencing using shotgun metagenomics. The first stool sample was collected 1 week pre-transplant and the second sample was collected 1-2 months post-transplant. Administered dose of Envarsus and Tac trough concentrations were recorded from day of transplant till 90 days post-surgery. Relative abundance of all bacterial genera was analyzed for detection of association with Envarsus dosage and potential inclusion in a dose selection model.

Results

All patients were high metabolizers of Tac by expressing either the homozygote or heterozygote CYP3A5*1 allele. Building upon the gene-guided dose selection model of Jacobson et al., we added the relative abundance of two bacterial genera as predictors of optimum Envarsus dose. Using a linear OLS regression model, the pre-transplant relative abundance of Phocaeicola in days<10 and the change in relative abundance of Bacteroides in 10<days<90 were predictors of optimum Envarsus dose with p<0.01. Our gene/microbiome-guided dose selection model is a better predictor for optimum dose of Envarsus compared to the gene-only dose selection model.

Conclusion

Personalized dose selection for high Tac metabolizers has been proven to improve transplant outcomes. For this purpuse we recommend using gut microbiome profile matched with gene marker information. In the next phase we will conduct a clinical trial to investigae the effectiveness of our dose selection model on transplant outcomes.

Funding

  • Commercial Support