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The effect of neonatal partial upper and lower urinary tract obstruction on the intestinal microbiome in a murine animal model.
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Broadwell Nora H, Lombardo Kara, Kohn Taylor P, Wu Charlotte Q, Kates Max R, Gearhart John P, Bivalacqua Trinity J
Аннотация
INTRODUCTION: The intestinal microbiome holds promise as a tool for prognostics, diagnostics, and interventions in patients with congenital anomalies of the kidney and urinary system. The goal was to characterize the neonatal rat intestinal microbiome in response to partial upper and lower urinary obstruction using 16S rRNA Illumina sequencing.
METHODS: Neonatal Sprague Dawley rats were operated on day three of life. Partial ureteral obstruction was performed in upper urinary tract obstruction (UUTO) via suture ligation. Partial urethral obstruction was created in lower urinary tract obstruction (LUTO) via clip-applier technique. The intestinal microbiome was evaluated via 16S rRNA gene amplicon sequencing. Alpha and beta diversity, single taxa abundance, and unique indicator species analysis was performed using R Statistical Software 4.2.0.
RESULTS: At 21 days post-operatively, body mass was higher in LUTO compared to UUTO (p = 0.003). Beta diversity clustered significantly between groups. LUTO had elevated Firmicutes:Bacteroidota ratios compared to UUTO (p = 0.014). A unique LUTO indicator was the absence of CAG-302 (p = 0.014). Lactobacillus_B was significantly downregulated in UUTO (p = 0.033). All unique indicators of UUTO derived from the Lachnospiraceae family.
CONCLUSION: This study evaluated the neonatal response of the gastrointestinal microbiome to urinary obstruction. LUTO resulted in high-risk microbiome profiles consistent with obesity and metabolic syndrome. UUTO rats had microbiome profiles consistent with CKD models, which modulate short chain fatty acids and uremic toxins. Such patterns in the intestinal microbiome may be used as a prognostic model to detect children at high-risk for organ damage secondary to obstructive uropathy.
METHODS: Neonatal Sprague Dawley rats were operated on day three of life. Partial ureteral obstruction was performed in upper urinary tract obstruction (UUTO) via suture ligation. Partial urethral obstruction was created in lower urinary tract obstruction (LUTO) via clip-applier technique. The intestinal microbiome was evaluated via 16S rRNA gene amplicon sequencing. Alpha and beta diversity, single taxa abundance, and unique indicator species analysis was performed using R Statistical Software 4.2.0.
RESULTS: At 21 days post-operatively, body mass was higher in LUTO compared to UUTO (p = 0.003). Beta diversity clustered significantly between groups. LUTO had elevated Firmicutes:Bacteroidota ratios compared to UUTO (p = 0.014). A unique LUTO indicator was the absence of CAG-302 (p = 0.014). Lactobacillus_B was significantly downregulated in UUTO (p = 0.033). All unique indicators of UUTO derived from the Lachnospiraceae family.
CONCLUSION: This study evaluated the neonatal response of the gastrointestinal microbiome to urinary obstruction. LUTO resulted in high-risk microbiome profiles consistent with obesity and metabolic syndrome. UUTO rats had microbiome profiles consistent with CKD models, which modulate short chain fatty acids and uremic toxins. Such patterns in the intestinal microbiome may be used as a prognostic model to detect children at high-risk for organ damage secondary to obstructive uropathy.