Weissella paramesenteroides M4: Optimization of bioprocesses, antioxidant property, and a potentially probiotic strain with in vitro activity against Cutibacterium acnes

The skin microbiota is linked to conditions such as acne. As antibiotic resistance limits the effectiveness of conventional treatments, microbiome-based strategies are needed. This study aimed to optimize the biomass production of Weissella paramesenteroides M4, evaluate its antioxidant properties, and assess its efficacy in a topical gel formulation against Cutibacterium acnes. Growth dynamics were established, followed by biomass optimization using fractional factorial and central composite rotatable designs with deproteinized whey as a sustainable substrate. Optimization increased biomass production by 974% (reaching 8.7 × 1010 CFU/mL, equivalent to 2.031 g/L dry weight under validated conditions); significant variables included yeast extract, peptone, and MnSO4. Antioxidant assays showed activities of 80% (intact cells) and 61% (lysed cells), with 82% relative growth under 1.0 mM H2O2 oxidative stress (estimated spectrophotometrically). Notably, W. paramesenteroides M4 selectively inhibited the pathogen C. acnes ATCC 6919 in vitro without affecting the commensal S. epidermidis ATCC 12,228 in vitro. A cosmetic gel containing the strain maintained antimicrobial efficacy and stability for 15 days at 4 °C. W. paramesenteroides M4 demonstrates high bioprocess efficiency, robust antioxidant potential, and selective in vitro antimicrobial activity. The formulated gel containing the candidate probiotic strain retained antimicrobial activity under refrigeration during storage and shows potential for innovative topical applications, providing a preliminary foundation for alternative acne management. This research provides a sustainable framework for high-yield probiotic production using industrial by-products and introduces a potentially probiotic lactic acid bacterium with selective in vitro activity, representing a promising candidate for alternative acne treatment, addressing a significant gap in current dermatological therapies. Graphical Abstract