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.