Abstract: FR-PO1031
Microbiome Encoded Enzymes and Mycophenolate Mofetil Enterohepatic Recirculation Parameters in Kidney Transplant Recipients
Session Information
- Transplantation: Clinical - Pharmacology and Nonkidney Solid Organ Transplants
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2102 Transplantation: Clinical
Authors
- Onyeaghala, Guillaume Chinedu, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
- Vo, Duy, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
- Gupta, Kajal, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
- Nguyen, Justin T, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
- Mohamed, Moataz, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
- Saqr, Abdelrahman, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
- Teigen, Levi, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
- Dorr, Casey R., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
- Staley, Christopher, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
- Guan, Weihua, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
- Khanipov, Kamil, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
- Golovko, George, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
- El-Rifai, Rasha, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
- Matas, Arthur J., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
- Remmel, Rory P., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
- Oetting, William S., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
- Jacobson, Pamala A., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
- Israni, Ajay K., The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
Background
Bacterial β-glucuronidases (βGUS) convert the inactivated mycophenolic acid glucuronide back to the active mycophenolic acid (MPA) through enterohepatic recirculation (EHR), likely enhancing immunosuppression and toxicity in kidney transplant recipients (KTRs). The diversity of these enzymes is not well defined in the microbiome of KTRs. We investigated the association between a sequencing panel of βGUS enzymes and pharmacokinetic (PK) parameters in KTRs.
Methods
Adult KTRs, 35 in prospective cohort (<6 months post-transplant) and 47 in cross-sectional cohort (2+ years post-transplant), underwent a 12hr MPA PK study with stool collection. Microbiome metatranscriptomics were processed with HUMAnN3 and matched against a BLAST panel of 279 βGUS enzymes from the human microbiome clustered gene indices (HMGC). In each cohort, BLAST-derived βGUS transcripts were corrected for the total number of reads and converted to copies per million (cpm) to compare with the Uniref90 database HUMAnN3 output. βGUS transcripts were associated with MPA %EHR (MPA AUC5-12/AUC0-12×100) and the number of EHR peaks during PK using Pearson correlations.
Results
βGUS transcripts were more abundant in HMGC BLAST compared to Uniref HUMAnN3 (mean cpm of 29512 vs 1.78 respectively). We identified 123 unique βGUS enzymes from HMGC. In the prospective cohort, the number of MPA EHR peaks was associated with both MPA EHR (r=0.52, p=0.01) and the relative abundance of βGUS transcripts (r= 0.35, p=0.03) (Table 1). In the cross-sectional cohort, no associations were found with PK or βGUS transcripts.
Conclusion
The relative abundance of βGUS was associated with the number of MPA peaks among KTRs in the early post-transplant period. The number of MPA peaks was also associated with MPA EHR in the same cohort. This suggests that these microbiome-encoded enzymes play a role in MPA variability, captured by the number of PK peaks. Developing in-vitro panels for βGUS enzymes will be necessary elucidate their clinical implications for EHR.
Funding
- Other NIH Support