Integrated microbiome and metabolome profiling in prepubertal girls with vulvar lichen sclerosus.

Vulvar lichen sclerosus (VLS) is a chronic anogenital disease with long-term risks of genital disfigurement and squamous cell cancer. The involvement of the gut-skin axis in prepubertal VLS remains unclear. We conducted a cross-sectional study of 43 prepubertal VLS patients and 46 healthy controls, performing fecal 16S rRNA sequencing and serum LC-MS to characterize gut microbiome-metabolome associations and identify altered microbial and metabolic signatures. We further assessed their exploratory classification performance using random forest models. No significant differences in alpha or beta diversity were observed between groups. At the nominal significance level, an increase in IMPORTANCE: Integrating gut microbiome and serum metabolome analyses, this study characterized gut-skin axis associations in prepubertal vulvar lichen sclerosus (VLS). Overall gut microbial diversity and community structure were preserved without statistically significant differences after multiple testing correction. However, linear discriminant analysis effect size identified discriminative taxa between groups, suggesting potential compositional differences at the feature level. In contrast, serum metabolomic profiles showed more robust alterations in VLS patients. The microbial and metabolic signatures demonstrated strong discriminative ability between VLS and control groups, supporting their potential as exploratory non-invasive biomarkers. These results indicate that modest gut microbiome-metabolome perturbations are early pathogenic events in VLS, preceding overt microbial structural remodeling, providing a reference for further exploration of early detection strategies in this condition. These findings suggest that VLS-related perturbations may be more evident at the metabolic than at the gut microbiome taxonomic level, providing a framework for future studies of gut-skin interactions and early disease characterization.