Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by impaired
epidermal barrier function and immune dysregulation. Emerging evidence suggests that
lipopolysaccharides (LPS) contribute to cutaneous inflammation and barrier disruption, but the
direct impact of LPS on skin barrier integrity in AD remains unclear. This study reviews the
current literature to evaluate how LPS exposure contributes to epidermal barrier dysfunction in
AD. A systematic review was conducted using a MeSH-guided PubMed search. Five reviewers
independently screened 27 articles using predefined inclusion criteria; discrepancies were
resolved by consensus. Eligible studies were published in English from 2010 onward and
analyzed LPS exposure and barrier-related outcomes in humans with AD and in vivo
keratinocyte models. Of 27 articles screened, 13 met the inclusion criteria. The included
literature demonstrates that LPS triggers a robust inflammatory response. At the cell surface,
LPS activates the TLR4 receptor complex, initiating MyD88 dependent signaling that drives NF
κB mediated production of pro-inflammatory cytokines. These effects were associated with
reduced expression of key barrier proteins, including filaggrin, loricrin, involucrin, and caspase
14, indicating impaired differentiation and barrier integrity. Overall, these findings support a
mechanistic link between LPS driven inflammatory signaling and epidermal barrier dysfunction
in AD. However, the evidence is limited to in vitro models, and further in vivo and clinical
studies are needed to confirm translational relevance. This review highlights LPS as a potential
contributor to AD pathogenesis and underscores the importance of investigating targeted
therapeutic strategies and environmental LPS exposure in patients with severe disease.
