Fecal β-glucuronidase activity differs between hematopoietic cell and kidney transplantation and a possible mechanism for disparate dose requirements

Mohammad Haneef Khan, Guillaume C. Onyeaghala, Armin Rashidi, Shernan G. Holtan, Alexander Khoruts, Ajay Israni, Pamala A. Jacobson, Christopher Staley

Research output: Contribution to journalLetterpeer-review

Abstract

The intestinal microbiota produces β-glucuronidase that plays an essential role in the metabolism of the immunosuppressant mycophenolate mofetil (MMF). This drug is commonly used in organ and hematopoietic cell transplantation (HCT), with variations in dosing across transplant types. We hypothesized that β-glucuronidase activity differs between transplant types, which may account for differences in dosing requirements. We evaluated fecal β-glucuronidase activity in patients receiving MMF post-allogeneic HCT and post-kidney transplant. Kidney transplant patients had significantly greater β-glucuronidase activity (8.48 ± 6.21 nmol/hr/g) than HCT patients (3.50 ± 3.29 nmol/hr/g; P = .001). Microbially mediated β-glucuronidase activity may be a critical determinant in the amount of mycophenolate entering the systemic circulation and an important factor to consider for precision dosing of MMF.

Original languageEnglish (US)
Article number2108279
JournalGut microbes
Volume14
Issue number1
DOIs
StatePublished - 2022

Bibliographical note

Funding Information:
The HCT study was supported by a University of Minnesota, Masonic Cancer Center Chainbreaker award, NIH grant P30CA077598, and the National Center for Advancing Translational Sciences of the National Institutes of Health P30CA077598, UL1-TR00249, R01AI140303 Award Number UL1-TR00249. The MISSION study was supported by NIH R01AI140303 from the NIAID. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health; Masonic Cancer Center, University of Minnesota;

Publisher Copyright:
© 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.

Keywords

  • Beta-glucuronidase
  • MMF
  • immunosuppression
  • intestinal microbiota
  • mycophenolate
  • transplantation

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

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