The brain–gut–skin axis in inflammatory and disfiguring skin diseases: mechanistic insights, clinical correlations, and therapeutic strategies

TL;DR

This review explores how the brain-gut-skin connection influences skin diseases and highlights new treatment strategies based on gut health and stress responses.

Contribution

The paper provides a comprehensive review of the brain–gut–skin axis and its role in skin diseases, emphasizing new therapeutic strategies and research needs.

Findings

Skin diseases like psoriasis and atopic dermatitis are linked to gut dysbiosis and neuroendocrine stress.

Microbiome-directed therapies and psychoneuroimmunological approaches show promise in treating these conditions.

More clinical validation and multi-omics studies are needed to establish causal relationships and improve precision treatments.

Abstract

Emerging evidence suggests that the brain–gut–skin axis (BGSA) plays a critical role in the pathogenesis of inflammatory and disfiguring skin diseases. Conditions such as acne, atopic dermatitis, psoriasis, rosacea, vitiligo, and alopecia areata, once regarded as localized disorders driven mainly by cutaneous immune dysfunction, are now recognized as systemic conditions associated with neuroendocrine stress responses, gut microbial dysbiosis, and chronic low-grade inflammation. Mechanistic studies elucidate the intricate interorgan communication mediated by microbial metabolites (e.g., short-chain fatty acids and tryptophan derivatives), cytokine networks, neuropeptides, and hypothalamic–pituitary–adrenal (HPA) axis signaling. Building on these insights, therapeutic strategies are evolving rapidly. Microbiome-directed interventions (probiotics, postbiotics, dietary modification, and fecal microbiota transplantation), together with psychoneuroimmunological approaches, have shown potential to alleviate disease severity. Integrative therapies, including traditional herbal medicine, offer promising effects; however, we emphasize that mechanistic depth and robust clinical validation for these modalities are currently limited. This review integrates mechanistic findings, clinical correlations, and emerging therapeutic approaches, while critically distinguishing between correlation and causation. Future studies should emphasize longitudinal multi-omics analyses and standardized clinical trials to clarify causal pathways and guide precision, patient-centered management for systemic and cutaneous health.

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