Heat-Treated Lactiplantibacillus plantarum Skinbac™ SB14 Supports Skin Barrier Function In Vitro and Reduces Dry Skin Cracking In Vivo

Background: The skin barrier plays a fundamental role in preventing transepidermal water loss (TEWL), regulating immune responses, and protecting against pathogen colonization. Disruption of this barrier underlies xerosis, sensitive skin, and clinical cracking. Heat-treated probiotics (postbiotics) represent a stable and biologically active approach to topical formulation. Objective: To evaluate the safety, molecular mechanisms, and clinical efficacy of heat-treated Lactiplantibacillus plantarum Skinbac™ SB14 (SB14) in improving skin barrier function, hydration, and the appearance of dry and cracked skin. Methods: In vitro studies assessed cell viability (MTT assay) and cytotoxicity (LDH release assay), Aquaporin-3 (AQP3) expression, Claudin-1 expression recovery following UV-induced damage (post-damage treatment model), cytokine modulation in Normal Human Epidermal Keratinocytes (NHEK) and Peripheral Blood Mononuclear Cells (PBMCs), and antipathogen activity against Staphylococcus aureus biofilm. A 30-day open-label, placebo-controlled clinical study (n = 20 healthy volunteers, both sexes, age > 18 years) evaluated an emulsion containing 1% SB14 versus placebo using instrumental measurements of superficial hydration (Corneometer® CM825) and TEWL (Tewameter® TM300), and clinical scoring of skin hydration (Kligman scale 1–4) and skin cracking (ODS Overall Dry Skin Score 1–5) via C-Cube imaging. Results: In vitro testing confirmed the safety of SB14 (full cell viability by MTT assay; no cytotoxicity by LDH release assay) and demonstrated significant AQP3 upregulation (p < 0.05), partial Claudin-1 recovery in UV-damaged cells following post-damage SB14 application (p < 0.1 vs. UV damage), significant reduction in pro-inflammatory IL-8 and IL-23 in NHEK (p < 0.01 and p < 0.05), strong innate immune activation in PBMCs (TNF-α and IL-6, p < 0.001), and 21% inhibition of S. aureus biofilm at 72 h. Clinically, the SB14 formulation significantly increased superficial skin hydration by +46.1% at T14 (p = 0.0451) and +33.6% at T30 (p = 0.0144) versus baseline, while TEWL decreased by −14.5% at T14 (p = 0.0205). Clinical hydration scores improved significantly from a median of 3.0 (moderate dry skin) at baseline to 2.0 (slightly dry skin) at T30 (p = 0.0073). Cracking scores improved significantly from a median of 3.5 at baseline to 2.0 at T30 (p = 0.0037), with 80% of subjects showing improvement at T30. All parameters remained non-significant in the placebo group. No adverse events were reported. Conclusions: SB14 is safe, biologically active across multiple barrier-relevant mechanisms, and clinically effective in improving hydration and reducing visible skin cracking in subjects with dry, barrier-compromised skin.