Harnessing the power of breast milk: how FN029 from rural western China mitigates severe atopic dermatitis in mice through retinol metabolism activation.

Tongwei and Wuxi represent a rural county in western China and an industrialized city in the east, respectively. The study compared breast milk and the corresponding infant gut microbiota from 35 healthy mothers in Tongwei and 28 in Wuxi, uncovering significant differences in microbial alpha and beta diversity. A unique strain, FN029, characteristically transmitted from breast milk to the infant gut in Tongwei, was identified. Oral administration of FN029 to weaned BALB/c mice significantly alleviated atopic dermatitis severity caused by calcipotriol and ovalbumin. This reduction was paralleled by a decrease in mast cells and eosinophils in ear tissue and reduced levels of IL-4, IL-12, IL-33, IFN-γ, the IL-4/IFN-γ ratio, and IgE in plasma, along with an upsurge in regulatory T cells in the spleen. RNA sequencing revealed that FN029 activated the retinol metabolism pathway and the Wnt signaling pathway, enhancing immature dendritic cells and regulatory T cells. Metabolomics analysis indicated an increase in retinyl beta-glucuronide, a biomarker of vitamin A reserves. The mRNA expression of retinol-metabolizing enzymes was inversely related to the IL-4/IFN-γ ratio. FN029 also altered ileum microbiota without a direct link to atopic dermatitis improvement. In conclusion, FN029, a probiotic from Tongwei breast milk, fostered T regulatory cell conversion and immune balance by activating the retinol pathway, thereby improving severe atopic dermatitis in mice.