Abstract:

Objective: To evaluate the relationship between urethral stricture and the urethral microenvironment following hypospadias surgery. Methods: Fifteen children who did not experience urethral stricture and 15 children who experienced urethral stricture within one year after hypospadias surgery were selected in this study, with similar clinical and follow-up data from January 2020 to December 2023. The urethral tissues were divided into three groups. The normal urethral tissues trimmed during initial treatment, from 15 children who did not develop urethral stricture within one year post-surgery, were categorized as the control normal tissue(CT) group. The normal tissues trimmed during the first treatment, from 15 children who developed urethral stricture within the same timeframe, were classified as the pre-stricture tissure (PST) group. The stricture urethral tissues trimmed during the subsequent surgical treatment, from the same 15 children with urethral stricture, were designated as the stricture tissue (ST) group. We explored the microbiome characteristics of the three groups using 16S rRNA sequencing, while transcriptome characteristics of the CT and ST groups were analyzed through transcriptome sequencing. A joint analysis was conducted to clarify the correlation between microbiome and transcriptome data. Results: The abundance of microbial colonies in the CT group was higher than that in the ST group, and there was no significant difference in this parameter between the ST group and the PST group. The microbial genera with the notable differences between the CT group and the ST group were included Muribacaceae, Prevotella, Peptoniphilus, Ezakiella, Escherichia, Bacteroides, Lachnospira, Lactobacillus, Dialister and Alistipes. A total of 1 413 differentially expressed genes were identified between the CT group and the ST group, with 1 060 genes (75.02%) upregulated and 353 genes (24.98%) downregulated in the ST group compared to the CT group. Integrated analysis suggested that transforming growth factor-β (TGF-β) and Smad4 may be associated with Escherichia coli. Conclusions: The imbalance in microbiota may contribute to urethral stricture, with a high abundance of Escherichia coli potentially inducing the stricture formation through the TGF-β/Smad signaling pathway.

Key words: Urethral stricture, Hypospadias, Microbiota, Transcriptome, Cluster analysis