Gut Microbiota, Metabolic Markers, and Systemic Inflammation in Young Women with Self-Reported Rosacea: An Exploratory Cross-Sectional Study.

Background: Rosacea is a chronic inflammatory dermatosis with emerging links to the gut-skin axis, yet integrative data connecting fecal microbiota with metabolic and immune parameters remain scarce. Methods: Within a cohort of Croatian women (N = 300, aged 30-35), participants with self-reported physician-diagnosed rosacea (n = 19) were compared to controls (n = 281). Assessments included validated questionnaires, anthropometrics, fasting blood parameters, and fecal 16S rRNA gene sequencing (QIIME2). Taxonomic profiling at four levels (899 features) used Mann-Whitney U tests with per-level Benjamini-Hochberg FDR correction. This study follows STROBE and STORMS guidelines. Results: On the host side, rosacea was nominally associated with higher BMI (p = 0.037), poorer sleep quality (p = 0.038), elevated monocytes (p = 0.031), and higher HOMA-B (p = 0.013); these comparisons were not corrected for multiple testing. Fecal 16S rRNA analysis (rosacea n = 18, controls n = 265) identified 15 nominally significant genera, including depleted Bifidobacterium (p = 0.007), Roseburia (p = 0.033), and enriched Anaerostignum (p < 0.001). However, no taxon survived FDR correction at any taxonomic level (lowest q = 0.165), and the total number of nominally significant features (48/899, 5.3%) did not exceed chance expectation (binomial p = 0.340). All key taxa remained nominally significant after BMI adjustment. An exploratory Random Forest classifier (five genera + HOMA-B + cortisol) achieved LOOCV AUC = 0.785, but feature selection on the training data limits interpretation. Conclusions: In this narrowly age-defined female cohort, host-side metabolic and immune differences reached nominal significance without multiple-testing correction. Fecal microbiota differences were exclusively exploratory: no taxon survived FDR correction, and the overall signal did not exceed chance expectation. The pattern of findings is compatible with-but does not constitute evidence for-a gut-skin axis contribution to rosacea. Confirmation in adequately powered cohorts with clinical rosacea verification, comprehensive confounder capture, and pre-registered analyses is required before any mechanistic or clinical conclusions can be drawn.