Gut commensal bacteria Parabacteroides goldsteinii-derived outer membrane vesicles suppress skin inflammation in psoriasis

Despite gut microbiota-derived extracellular vesicles (EVs) serving as pivotal mediators in bacteria-host cell interactions, their potential role in modulating skin inflammation remains poorly understood. Here, we developed strategies for mass production of Parabacteroides goldsteinii-derived outer membrane vesicles (Pg OMVs), commonly known as EVs. We found that orally administered Pg OMVs can reach the colon, traverse the intestinal barrier, and circulate to the inflamed skin of psoriasis-like mice, resulting in reduced epidermal hyperplasia, suppressed infiltration of inflammatory cells in the skin lesions, and effective amelioration of both skin and systemic inflammation. Additionally, subcutaneous injection of thermosensitive PF-127 hydrogel loaded with Pg OMVs exerts similar immunomodulatory effects, allowing sustained release of Pg OMVs into skin cells, effectively suppressing skin inflammation and ameliorating symptoms of psoriasis. This study unveils the importance of gut microbiota-derived OMVs, which can target inflamed skin via both the gut-skin axis and local skin administration, providing a promising alternative to live bacteria therapy for the treatment of skin inflammatory diseases.