The Indirect Role of <i>Staphylococcus aureus</i> in Atopic Dermatitis: A Comprehensive Analysis of MicroRNA-Mediated Mechanisms and Therapeutic Potential

Atopic dermatitis (AD) is a prevalent, chronic inflammatory skin disease, impacting up to 20% of children and 3% of adults globally. Its pathogenesis is rooted in genetic susceptibility and immune dysregulation, but colonization by <i>Staphylococcus aureus</i> is a well-established critical exacerbating factor. While traditional research has focused on the direct damaging effects of <i>S. aureus</i>, such as toxin release and superantigen-driven inflammation, new evidence points to a more nuanced, indirect pathway. This emerging paradigm highlights the bacterium's capacity to modulate host microRNA (miRNA) expression, representing a sophisticated epigenetic mechanism for worsening the disease.This review delivers a comprehensive analysis of the intersection between <i>S. aureus</i> infection and miRNA dysregulation in AD. It provides an extensive examination of shared miRNA signatures and offers detailed mechanistic insights into how specific bacterial virulence factors subvert host cellular processes to alter the miRNA landscape. The significant functional consequences of these changes are explored, demonstrating their detrimental impact on skin barrier integrity and the promotion of aberrant immune responses.Furthermore, we integrated a bioinformatic strategy to identify and validate common target genes and enriched biological pathways shared by AD and <i>S. aureus</i> infection. This systems-level perspective clarifies their synergistic role in driving disease pathogenesis. By synthesizing clinical findings from microbiology and dermatology with cutting-edge epigenetics and bolstering this synthesis with novel computational insights, this review offers a fresh perspective on AD pathogenesis. Ultimately, it pinpoints promising miRNA-directed avenues for future research and the development of innovative therapeutic strategies.