Multiomics and Structural Analysis of the Microcomedone Ecosystem Provides Insights Into the Clinical Efficacy of an Antiacne Formulation Containing <i>Silybum marianum</i> Fruit Extract

Background: Antiacne dermocosmetics are effective supportive care for managing mild‐to‐moderate acne. Exploration of the microcomedone ecosystem can provide insights into specific targets for antiacne products. Objective: To analyze changes in infra‐clinical acne lesions in subjects using a formulation containing Silybum marianum fruit extract (SMFE) to manage mild‐to‐moderate facial acne. Methods: A controlled, randomized, open‐label study was conducted in adults and adolescents with predominantly retentional acne lesions: the test group received the SMFE‐based product, and the control group received a hydrating skincare product. After evaluating the clinical efficacy of the study product, a multiomics approach was used to assess metabolome, lipidome, and microbiome changes in the microcomedone ecosystem. Two‐dimensional ultrastructural imaging was also performed on extracted microcomedones. Results: After 2 months of twice‐daily application of the study product, acne lesion severity was effectively reduced in the test group ( N = 20) compared to the control group ( N = 20). Ultrastructural imaging clearly showed alterations in microcomedones in the test group, which, together with evidence of decreased levels of several cellular components, demonstrated the comedolytic effect of the product. Specific changes also occurred at the microbiota and lipid levels: compared to controls, the relative abundance of Malassezia globosa fungi significantly decreased ( p &lt; 0.05), along with the levels of some proinflammatory lipids. These lipolytic fungi could be key targets of the antiacne product. Conclusion: Our integrative analysis demonstrated that the SMFE‐based product acts on the four main pillars of acne: hyperkeratosis, skin dysbiosis, hyperseborrhea, and proinflammatory lipids. Trial Registration: ClinicalTrials.gov Identifier: NCT05640388