P1754ASSOCIATION OF GUT MICROBIAL FERMENTATION WITH DIARRHEA IN KIDNEY TRANSPLANT RECIPIENTS

Abstract Background and Aims Diarrhea is a common complaint by kidney transplantation recipients (KTR). Metabolic abnormalities and immunosuppressive drugs may cause alterations in the gut microbiome possibly leading to diarrhea. A hydrogen (H2) breath test, reflecting nutrient fermentation, can detect changes in the composition of gut microbiota. In the present study, we studied the association of exhaled H2 with diarrhea in KTR, and investigated its determinants. Method All data were collected from the TransplantLines Biobank Cohort Study (NCT03272841). Living kidney donors were used as healthy controls. Breath H2 concentrations were analysed using solid state-sensor gas-chromatography. The stool water content was measured by faecal dry matter analysis and diarrhea was classified as >80% of water content in stools. Age, sex, body mass index (BMI), diabetes mellitus, eGFR and immunosuppressive medication were tested as potential determinants for H2 using linear multivariable regression. Results We included 424 KTR (mean age 55.4 ± 13.2 years, 39,1% female, transplant vintage 5.5 ± 9.5 years) and 164 healthy controls in this study. Immunosuppressive drugs included tacrolimus (78.5%), mycophenolate mofetil (MMF, 73.3%), cyclosporine (9.0%), and everolimus (2.4%) in various combinations. The median concentration of H2 in exhaled breath was significantly higher among KTR versus healthy controls (11.0 ppm [5.0 - 25.0] vs 9.0 ppm [4.0-22.5] p=0.005). The exhaled H2 was correlated with stool water content (r=0.24, p=0.04), as shown in figure 1. Serum tacrolimus trough levels were associated with exhaled H2 (standardized β=0.14, p=0.01), independent of age, sex, BMI, diabetes mellitus, eGFR and other immunosuppressive medication. In contrast, MMF trough levels were not independently associated with H2 (standardized β=0.07, p=0.21). Conclusion Exhaled H2, a marker of gut fermentation, is higher in KTR compared to healthy controls, and is associated with stool water content. Present results suggest that altered gut microbial fermentation contributes to the occurrence of diarrhea in KTR. Tacrolimus trough level was an independent determinant of H2. These data encourage further studies to validate the association of immunosuppressive drugs, gut microbiota and post-transplant diarrhea.