Skin Microbiome, Nanotoxicology, and Regulatory Gaps: Chronic Cosmetic Exposure and Skin Barrier Dysfunction-A...

Background: Engineered nanoparticles (NPs)-titanium dioxide, silver, zinc oxide and silica-are widely used in cosmetics for UV protection, antimicrobial activity and texturising effects. Chronic consumer-level exposure may impair skin-barrier integrity, disturb microbiome composition and dysregulate immune signalling via the gut-skin axis. Current regulatory frameworks typically omit chronic- or microbiome-focused safety assessments, leaving potential gaps. Objectives: This study aimed to evaluate the long-term effects of cosmetic-relevant NPs (titanium dioxide, silver, zinc oxide, silica) on skin and gut microbiota, epithelial-barrier integrity and immune signalling-including telocyte- and exosome-mediated pathways-and to identify regulatory shortcomings, particularly the absence of microbiome endpoints, validated chronic models and consideration of vulnerable populations. Methods: Following PRISMA 2020, PubMed, Scopus and Web of Science were searched for English-language in vivo animal or human studies (December 2014-April 2025) meeting chronic-exposure criteria (≥90 days in rodents or >10% of lifespan in other species; for humans, prolonged, repetitive application over months to years consistent with cosmetic use). Although not registered in PROSPERO, the review adhered to a pre-specified protocol. Two independent reviewers screened studies; risk of bias was assessed using a modified SYRCLE tool (animal) or adapted NIH guidance (zebrafish). Owing to heterogeneity, findings were synthesised narratively. Results: Of 600 records, 450 unique articles were screened, 50 full texts were assessed and 12 studies were included. Oral exposure predominated and was associated with dysbiosis, barrier impairment, immune modulation and metabolic effects. Dermal models showed outcomes from minimal change to pronounced immune activation, contingent on host susceptibility. Comparative human-animal findings are summarised; telocyte and exosome pathways were largely unexplored. Regulatory reviews (EU SCCS, US FDA and selected Asian frameworks) revealed no requirements for chronic microbiome endpoints. Limitations: Evidence is limited by the small number of eligible studies, heterogeneity in NP characteristics and exposure routes, predominance of animal models and a scarcity of longitudinal human data. Conclusions: Cosmetic nanoparticles may disrupt the microbiome, compromise barrier integrity and trigger immune dysregulation-risks amplified in vulnerable users. Existing regulations lack requirements for chronic exposure, microbiome endpoints and testing in vulnerable groups, and neglect mechanistic pathways involving telocytes and exosomes. Long-term, real-world exposure studies integrating gut-skin microbiome and immune outcomes, and harmonised global nanomaterial-safety standards, are needed to ensure safer cosmetic innovation.