Targeting Melanogenesis with Postbiotics: An Integrated Zebrafish-Based Assessment of Lactobacillus salivarius BGHO-1 and Lactobacillus paracasei BGSJ2-8

Skin hyperpigmentation disorders represent a major dermatological challenge, and safe alternatives to conventional depigmenting agents remain scarce. Probiotics and their postbiotic derivatives have emerged as promising natural candidates; however, only a few bacterial strains have been investigated for melanogenesis-inhibitory activity, and their true potential remains largely unexplored. Here, we report for the first time the biosafety profile and anti-melanogenic activity of <i>Lactobacillus salivarius</i> BGHO-1 and <i>Lactobacillus paracasei</i> BGSJ2-8, and assess their possible use in the treatment of skin hyperpigmentation. Two complementary zebrafish-based approaches were employed: (i) image-assisted analysis of pigmentation patterns, melanocyte morphology, and melanocytotoxicity, and (ii) quantitative melanin analysis, enabling integrated safety and efficacy evaluation. We investigated both native and heat-inactivated preparations, including whole cultures, cell-free supernatants, isolated cells, and separated cell walls/membranes and cytoplasmic fractions. While several fractions demonstrated the ability to inhibit melanogenesis, the cell wall/membrane fraction was the most potent, reducing melanin content by 64% compared to untreated embryos, while causing no systemic side effects and preserving melanocyte structure. Furthermore, this fraction did not elicit inflammatory responses or neutropenia, underscoring its favorable safety profile at anti-melanogenic doses. Collectively, this study identifies specific postbiotics as effective and safe modulators of melanogenesis and highlights their translational potential in developing novel approaches for treating skin hyperpigmentation.