Abstract
Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease with critical unmet therapeutic needs. This study compared the efficacy of three probiotics-Bifidobacterium animalis subsp. lactis J12 (B. animalis J12), Lactiplantibacillus plantarum Zhang-LL (L. plantarum Zhang-LL), and Limosilactobacillus salivarius M18-6 (L. salivarius M18-6)-in a 2,4-dinitrofluorobenzene (DNFB)-induced mouse AD model. Interventions included topical fermented supernatants (J12S/Z-LL-S/M18-6-S), oral live cells (J12L/Z-LL-L/M18-6-L), and topical dexamethasone (Dex) as the positive control. Post-intervention, AD-related pathological and immunological indices were evaluated. Among the three probiotics, J12 exhibited superior efficacy, whereas L. plantarum Zhang-LL and L. salivarius M18-6 showed limited therapeutic effects. Both J12-derived formulations alleviated DNFB-induced AD symptoms: Topical J12S significantly reduced ear swelling, serum IL-4 and IL-17 levels, and increased the proportion of splenic Treg cells. Oral J12L exerted comparable immunomodulatory effects, while further improving skin pathology-epidermal thickness and mast cell infiltration were each reduced to approximately one-third of those in the model group. Additionally, J12L regulated gut microbiota by enhancing alpha diversity and altering functional predictions. Collectively, B. animalis J12 is a promising candidate for AD management: topical J12S serves as an effective, non-invasive alternative to oral J12L. Notably, the two formulations act through distinct yet complementary mechanisms-J12L exerts systemic effects via regulating immunity and the gut-skin axis, while J12S exerts local anti-inflammatory effects and protects the skin barrier-highlighting J12's versatile therapeutic potential for AD.