Tea-derived exosome-like nanoparticles ameliorate atopic dermatitis by restoring gut microbiome homeostasis via enrichment of Parabacteroides goldsteinii

Atopic dermatitis (AD), a chronic inflammatory skin disorder often associated with gut microbiota dysbiosis, remains without safe and effective therapies. Tea-derived exosome-like nanoparticles (TELNs) possess anti-inflammatory and intestinal barrier–protective properties, yet their potential in AD has not been explored. In this study, TELNs were successfully isolated from tea leaves, with an average diameter of 77.1 nm and enriched in diverse functional proteins and metabolites. TELNs remained stable within the gastrointestinal tract and demonstrated therapeutic efficacy against AD. <em>In vitro</em>, TELNs were biocompatible and markedly suppressed inflammatory cytokines (TNF-α, IL-6) and chemokines (TARC, RNATES), while inhibiting NF-κB and JAK/STAT signaling pathways. In an AD mouse model, oral administration of TELNs alleviated clinical symptoms, improved skin barrier function, and reduced inflammation through these pathways. Mechanistically, TELNs restored gut microbiota imbalance induced by AD, notably enriching<em> Parabacteroides goldsteinii </em>(P<em>. goldsteinii</em>). Further experiments revealed that TELNs significantly promoted the growth of <em>P. goldsteinii</em> <em>in vitro</em>. Oral supplementation with <em>P. goldsteinii</em> effectively mitigated clinical symptoms and barrier dysfunction in AD mice, accompanied by reduced inflammatory cytokine production and suppression of NF-κB and JAK/STAT activation. Collectively, these findings demonstrate that TELNs ameliorate AD by modulating immune responses and reshaping gut microbiota, particularly through the enrichment of <em>P. goldsteinii</em>. This study highlights TELNs as promising, naturally derived nanotherapeutics for AD.