Abstract
Background: Acne vulgaris, a prevalent inflammatory skin disorder, stems from factors like Cutibacterium acnes overgrowth, inflammation dysregulation, and immune dysfunction. Clinically, acne severity inversely correlates with serum zinc (Zn) levels, and oral Zn supplementation shows efficacy. Lactic acid bacteria are capable of converting inorganic Zn into organic forms via biological transformation, potentially generating Zn-enriched bacteria as superior Zn delivery vehicles. Methods: In this study, a Zn-deficient acne mouse model was established through dietary Zn restriction combined with intradermal C. acnes injection. The therapeutic effects of orally administered Zn-containing supplements, including Zn-enriched Bifidobacterium longum subsp. longum CCFM1195 (Zn-CCFM1195), were systematically evaluated through multiple parameters: histopathological evaluation of skin lesions, cutaneous inflammatory and oxidative stress markers, serum Zn concentration, and gene expression levels of pathway-associated proteins. Results: Induction of C. acnes led to decreased serum Zn levels (14.98 μmol/L in Control vs. 9.71 μmol/L in Model) and skin metallothionein content, causing Zn imbalance. Zn deficiency caused increased levels of lesion elevation (9.23 in Model vs. 10.53 in Zn-deficient Model), IL-17A, TNF-α, and MMP9 in skin, thereby exacerbating the inflammatory response in C. acnes-induced mice. Zn supplementation alleviated inflammatory responses and oxidative stress in Zn-deficient acne-like mice. Notably, inactivated Zn-CCFM1195 exhibited superior efficacy to ZnSO(4), significantly reducing lesion diameter and decreasing cutaneous levels of IL-1β, IL-17A, and MDA while enhancing GSH-Px activity. Similarly, viable Zn-CCFM1195 treatment significantly decreased IL-17A and enhanced GSH-Px activity compared with ZnSO(4) treatment. Furthermore, Zn supplementation downregulated the expression of TLR2, IκBα, and IKKβ, which may exert its anti-acne effect by regulating related pathways. Conclusions: Zn deficiency exacerbates skin inflammation, whereas Zn supplementation, particularly with Zn-CCFM1195, alleviates acne vulgaris through anti-inflammatory and antioxidant effects.