Multi-omics analysis of outer membrane vesicles from P. goldsteinii in a psoriasis mouse model.

Aims: Psoriasis is a chronic skin inflammation with no complete cure. Parabacteroides goldsteinii (P. goldsteinii), a probiotic, alleviates inflammation by modulating gut microbiota. Its outer membrane vesicles (PG-OMVs) deliver microbial molecules to influence host-microbiota interactions. However, their role in psoriasis remains unclear. This study explores the effects and mechanisms of PG-OMVs in psoriasis.

Materials And Methods: PG-OMVs were isolated from P. goldsteinii using high-pressure tangential flow ultrafiltration combined with size exclusion chromatography, and characterized by transmission electron microscopy and nano-flow cytometry. Subsequently, Lipidomic and proteomic analysis was performed to investigate the composition of PG-OMVs. A psoriasis-like mouse model was established using imiquimod to evaluate their therapeutic effects. Furthermore, transcriptomic analysis, in situ sequencing, and 16S rRNA sequencing were applied to skin and fecal samples to explore underlying mechanisms. An in vitro model using LPS-stimulated HaCaT keratinocytes was also employed to assess the cytotoxicity and anti-inflammatory activity of PG-OMVs.

Key Findings: PG-OMVs have an average diameter of approximately 84.9 nm and a uniformly disc-like morphology. Lipidomic and proteomic revealed diverse lipid species and proteins potentially involved in regulating metabolic dysfunction. In the imiquimod-induced mouse model, PG-OMVs alleviated skin lesions and histopathological changes. Mechanistic studies showed that PG-OMVs modulate mTOR, TNF, and IL-17 pathways, regulate inflammatory and proliferative genes (e.g., AKT1, mTOR, FOS, FOSB), and restore gut microbial balance. In vitro, PG-OMVs significantly suppressed pro-inflammatory cytokines.

Significance: This study demonstrates that PG-OMVs ameliorate psoriasis by regulating inflammatory pathways and the gut microbiota, offering a promising therapeutic strategy.