Postbiotics derived from Lactobacillus paracasei CNCM I-5220 show beneficial effects on the skin

Keratinocytes represent our body’s first line of defense against the external environment: by producing inflammatory mediators, they actively participate in activating a protective immune response. However, the latter, if not controlled, can contribute to the pathogenesis of inflammatory skin diseases such as atopic dermatitis and psoriasis, which are also characterized by barrier abnormalities (Orsmond et al., 2021; G. Yang et al., 2020). A safe, tolerable, and long-term effective treatment for skin inflammation is needed. In addition to skin diseases, the ageing process impacts skin health and induces changes in keratinocytes and fibroblasts leading to skin roughness as well as loss of elasticity and hydration (Baumann, 2007; Chambers & Vukmanovic-Stejic, 2020). The maintenance of epithelial barrier homeostasis is mainly sustained by bacterial metabolites released during the natural fermentation process (Algieri et al., 2023), termed postbiotics (Tsilingiri et al., 2012; Tsilingiri & Rescigno, 2013). Therefore, we sought to investigate the beneficial effects of two novel postbiotics, LP-PBF and LP-PBL, derived from the Lactobacillus paracasei CNCM I-5220 strain, on skin functional proprieties. Although derived from the same bacterial strain, LP-PBF and LP-PBL showed different effects. Gene expression profiling of keratinocytes revealed an anti-inflammatory activity of LP-PBL, in particular by blocking the Poly (I:C)-dependent inflammatory pathways and consecutive recruitment of immune cells. Gene expression analysis confirmed that LP-PBL-treated cells inhibited the upregulation of Poly(I:C)-dependent proinflammatory cytokines including interleukin (IL)-23A, that is upregulated in psoriatic skin, IL-33 and long thymic stromal lymphopoietin (long TSLP) which are overexpressed in atopic dermatitis skin. Moreover, LP-PBL showed a barrier protective role suggesting its beneficial effects on damaged skin. By contrast, RNA sequencing results suggested a role of LP-PBF in counteracting age-induced processes, particularly by increasing the production machinery of hyaluronic acid in keratinocytes. In addition, LP-PBF stimulated the release of pro-collagen by dermal fibroblasts and promoted their migration, contributing to wound healing. To confirm the in vitro proposed functional roles of these postbiotics, clinical tests were performed on healthy volunteers. LP-PBL treatment reduced the redness on volunteers’ skin previously irritated by sodium lauryl sulfate, while, LP-PBF topically applied for six weeks on healthy volunteers’ skin, reduced skin roughness and increased hydration, elasticity, and echogenicity. Overall, we demonstrated that these postbiotics contribute to the maintenance of skin homeostasis, both in vitro and in clinical tests. These results indicate a potential role of LP-PBL and LP-PBF in counteracting inflammation and preventing age-induced skin changes, respectively. Our work highlights the versatility and potential benefits of postbiotic use for various health and wellness purposes.