Bifidobacterium animalis SMUDHYang01 enhances skin barrier function and alleviates atopic dermatitis via acetate secretion

Summary: Abstract Body: Dysbiosis in the gut microbiota has been implicated in the pathogenesis of atopic dermatitis (AD). Using faecal shotgun metagenomic sequencing, Bifidobacgterium spp, including B. bifidum, B. breve, B. longum and the B. animalis, were found to be depleted in patients with AD (n = 30) compared with healthy subjects (n =20). Among these, B. animalis was specially shown to alleviate MC903-induced mouse AD. We successfully isolated the B.animalis from healthy human fecal samples, and the strain identification was confirmed through whole-genome sequencing. Notably, the newly isolated strain SMUDHYang01 significantly improved the severity of MC903-induced AD-like lesions in a mouse model, as evidenced by reduced ear thickness, improved epidermal thickness, decreased mast cell infiltration, and lower plasma IgE levels, compared to E. coli MG1655 or BHI-treated mice (All measures, P < 0.05, n = 10). Further investigations revealed that both live SMUDHYang01 and its cultured supernatant (CS) effectively alleviated dermatitis. In contrast, heat-inactivation of SMUDHYang01 abolished this effect, suggesting that metabolite(s) derived from SMUDHYang01 contributed to its preventive capacity against AD. Unbiased LC-MS/MS analysis of metabolites identified that acetate was enriched in SMUDHYang01-CS (16.4-fold, P < 0.0001), as well as in the gut and skin biopsies of SMUDHYang01-treated mice. Accordingly, administration of acetate alone or oral administration of engineered acetate-producing E. coli significantly inhibited the progression of AD in the murine model. Mechanistically, acetate translocate into the keratinocyte cytoplasm and binds to STAT-6 via Monocarboxylate transporter1 (MCT1) transport, leading to reduced nuclear translocation of p-STAT-6. This further mitigates IL-4-mediated reduction in claudin-1 and claudin-4, thereby restoring skin barrier function. Overall, SMUDHYang01 emerges as a novel prophylactic agent for AD prevention, exerting its skin barrier-protecting effects through gut microbiota modulation and the secretion of acetate. Yanqiang Shi¹, Qing Li¹, Bin Yang¹ 1. Dermatology Hospital, Southern Medical University, Guangzhou, Guangdong, China. Innate Immunity, Microbiology, and Microbiome