Revisiting Rosacea Through the Skin-Gut-Brain Axis: A Neuroimmune Perspective.

Rosacea is increasingly recognized as a complex inflammatory disorder extending beyond isolated cutaneous pathology, involving dysregulated interactions between the skin, gastrointestinal system, and central nervous system. The skin-gut-brain axis has emerged as a relevant conceptual framework for understanding this multifactorial disease, integrating gut microbiota dysbiosis, neuroimmune signaling, autonomic nervous system dysfunction, and stress-related mechanisms. The aim of this narrative hypothesis-driven overview is to reframe rosacea as a neuroimmune disorder in which central nervous system involvement plays an active regulatory role, rather than as a purely peripheral or dermatological condition. We synthesize the mechanistically relevant evidence linking gastrointestinal inflammation and microbial imbalance with neurogenic inflammation, mast cell activation, sebaceous gland dysfunction, and aberrant innate immune responses in the skin, with particular emphasis on neurovascular and trigeminal pathways. A key novelty of this perspective lies in highlighting brain-centered mechanisms, including central sensitization, autonomic dysregulation, and stress-related neural modulation, as integral components of the skin-gut-brain axis in rosacea. By integrating peripheral and central processes, we propose rosacea as a model condition for studying neuroimmune dysregulation across interconnected regulatory systems. Finally, we discuss the clinical and translational implications of this framework and outline future research directions, focusing on autonomic regulation, patient stratification, and personalized, multidisciplinary therapeutic approaches.