Bacteroides fragilis outer membrane vesicle mediates Pseudomonadota colonization by inducing autophagy on the skin

Skin homeostasis is essential for host defense. Though constantly exposed to the external environment, signals from anaerobes have been detected in deeper skin layers, with their functional role in cutaneous immunity remaining unclear. Here, we explored whether skin-associated Bacteroidota contribute to pathogen exclusion via host autophagy. Comparative analysis of the skin microbiota revealed a progressive reduction in Pseudomonadota abundance alongside an increase in Bacteroidota during childhood-to-adulthood transition. A significant inverse correlation between Bacteroidota and Pseudomonadota abundance was observed in pediatric cohorts. Bacteroides fragilis and its secreted outer membrane vesicles (OMVs) induced autophagy, which facilitated Pseudomonadota clearance in macrophages. In vivo colonization experiments showed that live B. fragilis bacteria or intact OMVs outcompeted Pseudomonadota in wild-type mice, but not in lc3a -/- mice. These findings provide a plausible model explaining the inverse association detected in human cohorts, indicating that B. fragilis may help suppress potentially pathogenic taxa like Pseudomonadota on the skin.