Sex-Specific Dysbiotic Bladder Microbiome in CKD Uncovered via High-Throughput Sequencing and Culture

Abstract

Abstract Background High-throughput techniques confirm the human bladder microbiome, but its relation to chronic kidney disease (CKD) remains unexplored. Bladder bacteria may migrate to the kidneys, affecting CKD. Methods A cross-sectional study recruited 66 females diagnosed with CKD, 66 males diagnosed with CKD, as well as 22 HCfemales and 22 healthy control (HC) males. Transurethral catheterized urine and fecal samples were collected for 16S rRNA gene sequencing and EQUC. Urinary analysis, kidney function, and serum cytokines were evaluated. Results Bladder 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 a depletion of 5 genera, including Lactobacillus, and enrichment of 14 genera, including Escherichia/Shigella, Bifidobacterium, and several clostridial genera (FDR < 0.05), while EQUC detected increased Escherichia and decreased Lactobacillus CKDB (P < 0.05). Escherichia-Shigella was positively associated, whereas Lactobacillus was negatively associated, with CKDB-female serum creatinine (r = 0.285, P = 0.020; r=-0.337, P = 0.006, respectively). Lactobacillus was 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). Conclusions CKD bladder microbiomes were dysbiotic, especially in females, associated with kidney damage and serum cytokine dysregulation. Increased bladder-fecal microbiome similarity in CKD females implies potential “leaky gut”.