Kidney Week

Abstract: TH-PO123

Gut Microbiome Signature Associated with Mycophenolate Mofetil Enterohepatic Recirculation

Session Information

• Pharmacology
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

• 2000 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

• Onyeaghala, Guillaume Chinedu, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States

Guillaume Chinedu Onyeaghala, PhD, MPH

• Vo, Duy, Hennepin Healthcare Research Institute, Minneapolis, Minnesota, United States

Duy Vo

• Brito Sanchez, Bryan P., Hennepin Healthcare Research Institute, Minneapolis, Minnesota, United States

Bryan P. Brito Sanchez

• Saqr, Abdelrahman, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States

Abdelrahman Saqr, MS

• Mohamed, Moataz, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States

Moataz Mohamed, MSc

• Staley, Christopher, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States

Christopher Staley, PhD

• Teigen, Levi, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States

Levi Teigen, PhD, RD

• Dorr, Casey R., Hennepin Healthcare Research Institute, Minneapolis, Minnesota, United States

Casey R. Dorr, PhD

• Guan, Weihua, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States

Weihua Guan

• El-Rifai, Rasha, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States

Rasha El-Rifai, MD

• Matas, Arthur J., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States

Arthur J. Matas, MD

• Remmel, Rory P., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States

Rory P. Remmel, PhD

• Oetting, William S., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States

William S. Oetting, PhD

• Jacobson, Pamala A., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States

Pamala A. Jacobson, PharmD

• Israni, Ajay K., Hennepin Healthcare Research Institute, Minneapolis, Minnesota, United States

Ajay K. Israni, MD, MS

Background

Bacterial b-glucuronidase (BGUS) converts mycophenolic acid glucuronide back to mycophenolic acid (MPA) through enterohepatic recirculation (EHR), likely enhancing immunosuppression and toxicity in kidney transplant recipients (KTRs). We hypothesized that BGUS producing gut taxa are associated with EHR in KTRs.

Methods

Adult KTRs (n=84, 37 prospective and 47 cross-sectional) underwent simultaneous pharmacokinetic(PK) study and stool collection (71 KTRs completed a pre-PK 48hr food recall). We defined MPA %EHR as MPA AUC_{5-12 hr} / AUC_{0-12 hr} x100. Microbiome shotgun data were processed with HUMAnN3 and differentially abundant taxa associated with EHR adjusted for cohort were identified with MaAsLin2. We further adjusted for age, sex, diet and standardized creatinine clearance using zero inflated Poisson regression. In an exploratory analysis stratified by cohort, we compared the relative abundances of 12 known BGUS producers across EHR levels using the Wilcoxon sum rank test.

Results

Higher relative abundances of Blautia obeum and Faecalibacillus intestinalis were associated with high EHR (p=0.007 and <0.001 respectively), whereas high Gordonibacter pamelaeae abundance was associated with low EHR (p= 0.001) (FIG 1). In our exploratory analysis, high Collinsella aerofaciens abundance was associated with high EHR in the prospective cohort(p=0.04). Alpha or beta-diversity at the time of PK were not associated with EHR.

Conclusion

Our findings suggest a microbiome signature including Blautia, a known BGUS producing taxa, associated with MPA EHR after adjusting for age, sex, diet, and standardized creatinine clearance at the time of PK. Future BGUS assesments may provide opportunities to facilitate MMF dosing based on the stool microbiome.

Funding

• NIDDK Support