The bladder microbiome of chronic kidney disease with associations to demographics, renal function, and serum cytokines

Abstract

BackgroundHigh throughput 16S rRNA gene sequencing and enhanced culture methods (e.g., expanded quantitative urine culture, EQUC) have established the existence of the human bladder microbiome. We aim to test the hypothesis that the bladder environment of patients with chronic kidney disease (CKD) differs from that of unaffected controls with associated consequences for the composition of the bladder microbiome.Methods and MaterialsFemales (n=66) and males (n=66) diagnosed with CKD and age-BMI-matched healthy control (HC) females (n=22) and males (n=22) were recruited. Transurethral catheterized urine was collected for 16S rRNA gene sequencing and Expanded Quantitative Urine Culture (EQUC). Fecal samples also were sequenced. Urinary analysis, kidney function and serum cytokines were examined.ResultsBladder microbiomes of CKD females and males versus HC females and males differed (FDR<0.05); however, the difference was more obvious in females. In CKD females, sequencing revealed depletion of 5 genera, includingLactobacillus, and enrichment of 14 genera, includingEscherichia/Shigella, Bifidobacterium, and several clostridial genera (FDR<0.05), while EQUC detected increasedEscherichiaand decreasedLactobacillusCKDB(P<0.05).Escherichia-Shigellawas positively, whereasLactobacilluswas negatively, associated with CKDB-female serum creatinine (r=0.285, P=0.020; r=-0.337, P=0.006, respectively).Lactobacilluswas positively associated with eGFR (r=0.251, P=0.042). Some CKD-related serum cytokines were negatively associated with clostridial genera. In contrast, the fecal microbiomes of CKD and HC females and males did not significantly differ in bacterial diversity or composition. However, bladder and fecal microbiomes of CKD females resembled each other more than those of controls, as assessed by the Bray-Curtis Dissimilarity Index (FDR<0.05).ConclusionsCKD bladder microbiomes were dysbiotic, which was more obvious in females. This dysbiosis was associated with kidney damage severity and dysregulation of serum cytokines. The increased similarity between bladder and fecal microbiomes of CKD females suggests possible “gut-leakage.”