Intestinal permeability and therapeutic implications of the gut-skin axis in acne vulgaris: the emerging role of zonulin-related immunoreactivity – a narrative review

Aim: This narrative review evaluates evidence concerning the potential relationships among intestinal permeability, zonulin-related immunoreactivity, the gut-skin axis, and acne vulgaris.Methods: A narrative, non-exhaustive review of literature published from 2000 to July 2026 was conducted using PubMed, Scopus, and Web of Science, with the final literature search performed on 20 July 2026. Clinical studies, review articles, and experimental publications addressing zonulin, intestinal permeability, the gut-skin axis, the gut microbiome, diet, inflammatory pathways, and microbiome-targeted interventions were selected according to thematic relevance. A total of 55 publications were included in the final narrative synthesis; no systematic screening protocol or formal risk-of-bias assessment was applied.Results: Current evidence suggests biologically plausible links among intestinal barrier dysfunction, microbial dysbiosis, systemic inflammation, and metabolic pathways relevant to acne vulgaris. The only direct acne-specific study identified reported higher circulating zonulin-related immunoreactivity in patients with acne vulgaris than in healthy controls; however, its cross-sectional design and reliance on a commercial ELISA preclude conclusions regarding functional intestinal permeability or causality. Evidence from non-acne populations and other inflammatory dermatoses provides additional support for associations between altered barrier-related biomarkers and systemic inflammation. However, these findings cannot be directly extrapolated to acne. Dietary and microbiome-targeted interventions, including probiotics and synbiotics, have shown potential clinical benefit, although available studies remain limited and heterogeneous. Overall, the evidence supports biological plausibility but does not establish a causal zonulin-mediated gut-skin pathway in acne vulgaris.Conclusion: Altered intestinal permeability represents a biologically plausible but unproven component of the gut–skin axis in acne vulgaris. Current evidence does not establish a causal pathway connecting intestinal permeability, microbial translocation, systemic inflammation, metabolic signalling, and sebum production. Circulating zonulin-related immunoreactivity should be interpreted cautiously and does not independently establish functional intestinal permeability. Longitudinal studies incorporating validated functional permeability measures are required.