Gut Microbiota and Uremic Retention Solutes in Adults With Moderate CKD: A 6-Day Controlled Feeding Study

Abstract

To determine serum and urine concentrations of the uremic retention solutes (URSs), indoxyl sulfate (IS), p-cresol sulfate (PCS), and trimethylamine N-oxide (TMAO), and gut microbiota composition in individuals with moderate chronic kidney disease (CKD) compared with matched adults without CKD in a 6-day controlled feeding study. This study was a secondary analysis in which 8 adults with moderate CKD were matched for age, sex, and race with 8 adults without CKD in a parallel-arm, 6-day controlled feeding study. IS, PCS, and TMAO were quantified using liquid chromatography-mass spectrometry in fecal samples, fasting serum, and fasting spot urine samples collected at the end of the feeding period. Fasting serum URS concentrations were 2.8 to 4.9x higher in CKD compared to controls (all P<.05). No differences were found in the composition of the gut microbiota between patients with and without CKD when analyzing samples for α-diversity, β-diversity, and only minor abundance differences across taxa were apparent. Estimated glomerular filtration rate (eGFR) was inversely related to each serum URS in the whole cohort (all P<.01). However, within groups the relationships between eGFR and serum URS remained strong for CKD patients for IS and TMAO (both P<.05) but weakened for PCS (P=.10). eGFR was only correlated with urine PCS in the whole cohort (P=.03); within groups, no correlation for eGFR with any urine URS was observed. Only urine TMAO was higher in CKD compared to controls (P<.05). Serum URS concentrations are elevated in adults with CKD compared to matched non-CKD adults without differences in gut microbiota composition after consuming the same controlled study diet for 6days. Future studies are needed to determine if specific dietary components may differentially alter the microbiota and URS.