ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-PO799

Association Between Fecal MicroRNAs and B-Glucuronidase Activity in Kidney Transplant Recipients

Session Information

Category: Transplantation

  • 2002 Transplantation: Clinical

Authors

  • Onyeaghala, Guillaume Chinedu, Hennepin Healthcare Research Institute, Minneapolis, Minnesota, United States
  • Elmer, Sarah, Hennepin Healthcare Research Institute, Minneapolis, Minnesota, United States
  • Khan, Mohammad Haneef, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Yang, Pa Chia, Hennepin Healthcare Research Institute, Minneapolis, Minnesota, United States
  • Wagner, Matilda, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Teigen, Levi, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Wu, Baolin, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Guan, Weihua, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Staley, Christopher, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Matas, Arthur J., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Riad, Samy M., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Dorr, Casey R., Hennepin Healthcare Research Institute, 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., Hennepin Healthcare Research Institute, Minneapolis, Minnesota, United States
Background

The inactivated metabolite of Mycophenolate mofetil is de-glucuronidated by gut bacterial beta-glucuronidase and the active metabolite MPA is reabsorbed back into the blood. This enterohepatic recirculation likely enhances immunosuppression and toxicity in kidney transplant recipients. Further, host microRNA (miRNA) can influence the microbiome, leading to changes in b-glucuronidase levels. We hypothesized that host miRNA levels would be associated with b-glucuronidase levels in kidney transplant recipients.

Methods

In this analysis, 30 stool samples were collected from participants of the Microbiome and Immunosuppression in Kidney Transplantation (MISSION) study within 60 days post-transplant. Fecal miRNA was profiled using the nCounter human v3 miRNA codeset. b-glucuronidase activity levels were measured using the ab234625 Assay Kit. After QC and data normalization, we examined the association of 798 miRNA probes with b-glucuronidase activity. In a secondary analysis, we conducted focused analyses of 17 microbiome associated fecal miRNAs and their association with b-glucuronidase activity.

Results

At the Bonferroni corrected 0.05 significance level, we found 20 fecal miRNAs associated with b-glucuronidase activity, with miR-2116-5p, miR-4888 and miR-600 being the most abundant. In our focused analyses, we found that miR-1253, miR-1224-5p, miR-194-5p and miR-200a-3p were associated with b-glucuronidase activity (p-value < 0.05). Interestingly, miR-1224-5p was shown to align with E. coli DNA, while miR-1253 was shown to align with F. nucleatum DNA (Figure 1), which are known producers of b-glucuronidase enzymes.

Conclusion

Our preliminary findings show that fecal miRNAs are associated with b-glucuronidase. Further mechanistic studies are needed to validate these findings. Fecal miRNAs may enter bacteria, such as E. coli and F. nucleatum and potentially regulate bacterial growth or gene transcripts such as b-glucuronidase.