{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T05:13:21Z","timestamp":1789881201141,"version":"4.0.1"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 81974085"],"award-info":[{"award-number":["No. 81974085"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Discipline Leader of Shanghai Municipal Health","award":["No. 2022XD015"],"award-info":[{"award-number":["No. 2022XD015"]}]},{"name":"the Summit Plateau Program, Research Physician Program, Shanghai Jiao Tong University School of Medicine","award":["No. 20240817"],"award-info":[{"award-number":["No. 20240817"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,10,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Male genital lichen sclerosus-induced urethral stricture is a chronic inflammatory disease with significant microbiota dysbiosis. However, dysbiosis inside lesion tissue and its correlation with gene expression in male genital lichen sclerosus (MGLSc) remain elusive. This study investigated the influence of host-microbe interactions on dysbiosis and differential gene expression in MGLSc. Microbiome and transcriptome sequencing were conducted using prepuce samples from 27 MGLSc patients and 17 controls. We also performed immunohistochemistry staining of bacterial markers on prepuce tissue from two cohorts. Furthermore, potential risk factor information available from the MGLSc clinical data was collected and correlated with the differential microbiota. Unclassified Muribaculaceae and\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      were enriched, while\n                      <jats:italic toggle=\"yes\">Finegoldia magna<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Prevotella timonensis<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Bacillus pumilus<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">Peptoniphilus harei<\/jats:italic>\n                      , etc., were reduced in MGLSc tissues and decreased in gram-positive bacteria (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.05). The functions of differentially expressed genes (DEGs) were associated with immune activation, inflammatory response, innate immunity, and pathogen response. DEGs related to pathogen recognition, such as\n                      <jats:italic toggle=\"yes\">TLR1<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">TLR2<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">TLR6<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">HLA-DOB<\/jats:italic>\n                      , were upregulated (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.05). Single-sample gene set enrichment analysis revealed MGLSc lesions enriched immune cells. Clinical correlation analysis indicated that differential microbota was negatively correlated with age (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.05) and stricture grade (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.05) and was positively correlated with total cholesterol levels (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.05), body mass index (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.05), and triglyceride levels (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.05). Our study provides preliminary clues on host-microbe interactions in MGLSc development, suggesting that tissue dysbiosis may be associated with localized immune dysregulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Our study combined full-length 16S rDNA sequencing, transcriptome data, and clinical information from MGLSc patients to explore the relationships between host-microbe interactions and the development of tissue dysbiosis in MGLSc. Importantly, through staining for lipopolysaccharide and lipoteichoic acid, as well as full-length 16S rDNA sequencing, we identified, for the first time, the presence of microorganisms distribution pattern in lichen sclerosus prepuce tissue. Significant differences in the abundance of unclassified Muribaculaceae,\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Finegoldia magna<\/jats:italic>\n                      , and other taxa were observed between the prepuce of MGLSc patients and controls. These differences were associated with altered gene expression in MGLSc patients, while the differential microbiota, in turn, influenced host gene expression. Although patterns of host-microbe interactions varied across populations, dysbiosis was linked to key clinical indicators in MGLSc patients. These findings provide valuable insights into the role of dysbiosis in MGLSc pathogenesis, laying a foundation for understanding disease progression and identifying potential biomarkers.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.00074-25","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T12:00:43Z","timestamp":1755518443000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["Multi-omics analysis reveals the host-microbe interactions on the dysbiosis of tissue microbiota in male genital lichen sclerosus-induced urethral strictures"],"prefix":"10.1128","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2861-2182","authenticated-orcid":false,"given":"Zhenwei","family":"Yu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0220qvk04","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of 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