*Purpose: The treatment of mycophenolate mofetil (MMF)-related diarrhea in kidney transplants recipients often involves dose reductions, which may result in less effective immunosuppression. We hypothesize that bacterial beta-glucuronidase activity, which is a key enzyme in MMF enterohepatic recirculation, is associated with diarrhea occurrence.

*Methods: The ongoing Microbiome and Immunosuppression in Kidney Transplantation study used Mosio to implement a HIPPA compliant text-based diarrhea survey. The survey was sent on a bi-weekly basis to 24 participants receiving MMF and tacrolimus, for up to 3 months post-transplant. The participants were dichotomized by diarrhea grade (grade 0-1 vs >= grade 2) using the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE). Each participant provided a single stool sample collected within 21 days of transplant (baseline), which underwent metatranscriptomics analysis on NovaSeq. The sequence data were processed using HUMAnN 3.0, and beta-glucuronidase transcripts were determined using level-4 enzyme commission (EC) categories and normalized to copies per million (cpm). In an exploratory analysis, we used polytomous logistic regression to model the association between diarrhea events and beta-glucuronidase transcripts after controlling for age, gender, race, diabetes and BMI at baseline.

*Results: Participant characteristics are presented in Table 1. Over 3 months of follow up, 582 surveys were completed and 25 out of 56 diarrhea events were CTCAE grade 2 (Figure 1). Although beta-glucuronidase levels in the stool were lower among participants who developed CTCAE grade 2 diarrhea (mean of 71.2 cpm, vs 107.4 cpm in CTCAE grade 0 participants) we did not observe an association between beta-glucuronidase transcripts and diarrhea (RR: 0.999, p-value: 0.38) (Table 2).

*Conclusions: This preliminary analysis did not find an association between baseline levels of beta-glucuronidase transcripts and diarrhea occurrence during a 3-month follow-up period. A larger sample size is needed to simultaneously collect longitudinal microbiome data and MMF adverse events to understand the interplay between the gut microbiome and MMF adverse events in kidney transplantation.

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