CCFM1078 alleviates DNFB-induced atopic dermatitis in early-lifeAhR activation, Th1/Th2 immune modulation, and gut microbiota regulation.

Abstract

Atopic dermatitis (AD), a prevalent allergic skin disease characterized by a Th2-dominant inflammatory response, imposes a significant global health burden. Early-life serves as a pivotal period for intestinal microbial establishment, which critically influences immune system development and has lasting implications for health into later life. This study evaluated the therapeutic potential of early-life intervention withCCFM1078 on DNFB-induced atopic dermatitis in a murine model. Intervention withCCFM1078 significantly alleviated AD manifestations, such as ear swelling and epidermal hyperplasia. These improvements were associated with diminished inflammatory cell infiltration, lowered serum IgE levels, and reduced expression of key pro-inflammatory cytokines (IL-4, IL-13, CCL-22) in skin tissues, alongside elevated levels of IFN-γ and the anti-inflammatory cytokine IL-10. Additionally, the intervention boosted both IgA and secretory IgA (sIgA) levels in the colon. Mechanistically,CCFM1078 activated the aryl hydrocarbon receptor (AhR) signaling pathway, leading to the upregulation of CYP1A1, Gal-1, and Gal-3, and suppressed TSLP production. It also favorably altered gut microbiota composition by enriching beneficial bacterial taxa. In summary, early-life administration ofCCFM1078 alleviates AD symptoms through concurrent modulation of the AhR pathway, restoration of Th1/Th2 immune balance, and beneficial restructuring of gut microbiota.