Multi-omics analysis reveals the host-microbe interactions on the dysbiosis of tissue microbiota in male genital lichen sclerosus- induced urethral strictures

Background Male genital lichen sclerosus-induced urethral strictures (MGLSc-US) is a chronic inflammatory disease with significant microbiota dysbiosis. The impact of this dysbiosis on disease progression and gene expression in MGLSc lesions still has a knowledge gap. This study investigated the influence of microbiome-host interactions on microbial dysbiosis and differential gene expression in MGLSc by analyzing the microbiome and transcriptome of foreskin tissues. Results Microbiome and transcriptome sequencing were conducted using prepuce samples from MGLSc patients (n = 27) and controls (n = 17). In MGLSc patients, unclassified Muribaculaceae and Escherichia coli. were enriched, while Finegoldia magna , Prevotella timonensis , Bacillus pumilus , and Peptoniphilus harei etc., were reduced. No differences in alpha diversity were observed, but beta diversities were significantly different ( p  < 0.05) compared to controls. The microbial community exhibited a decrease in Gram-positive bacteria ( p  < 0.05). The top 15 GO pathways of differentially expressed genes (DEGs) were associated with immune activation, inflammatory response, and innate immunity and pathogen response. Single sample gene set enrichment analysis revealed MGLSc lesions enriched immune cells, including activated CD4 T cells ( p  < 0.0001), effector memory CD4 T cells ( p  < 0.0001), activated B cells ( p  < 0.001), and Type 2 Helper T cells ( p  < 0.001). DEGs related to pathogen recognition, such as TLR1, TLR2, TLR6, and HLA-DOB, were upregulated ( p  < 0.05). Clinical correlation analysis indicated that Escherichia coli negatively correlated with age ( p  < 0.01). The unclassified Muribaculaceae was positively correlated with total cholesterol levels ( p  < 0.001). The abundance of Peptoniphilus sp. S470 was positively correlated with body mass index ( p  < 0.05). The abundance of Bacillus pumilus was positively correlated with triglycerides levels ( p  < 0.05). Enterococcus faecalis ( p  < 0.05) and Staphylococcus epidermidis ( p  < 0.01) were negatively correlated with stricture grade. Conclusions This study, based on microbiota and transcriptomics, was the first to discover a decrease in Gram-positive bacteria in the lesional prepuce tissue of MGLSc patients. In the MGLSc population, dysbiosis was associated with pathogen-response immune pathways. Additionally, patient clinical characteristics were correlated with the abundance of differential microbe.