Bifidobacterium lactis Derived Vesicles Attenuates Hippocampal Neuroinflammation via Targeting IL-33 to Regulate FoxO6/P53 Signaling

Hippocampal Neuroinflammation (HNF) is a critical driver of cognitive impairment. The lipo-polysaccharide (LPS) accumulate amyloid beta (Aβ) and lead to HNF. The Bifidobacterium lactis (BL) 99 have anti-inflammatory ability. However, the whether BL99-derived microbiota-derived vesi-cles (MV) could alleviate LPS induced HNF remain unclear. To investigate, we used ultrafiltration with ultracentrifuge to extract BL99-derived-MV (BL99-MV). We used hippocampal neuronal HT22 cells (HT22) to establish LPS induced HNF model, and ex-plored BL99-MV alleviate LPS induced HNF. The confocal microscopy showed that BL99-MV were taken up by HT22 and reduced oxidative stress (ROS) level. The PCR showed that BL99-MV up-regulate IL-10 level, down-regulate TNF-α, IL-1β and IL-6. Transcriptomic analysis revealed that 4,127 differentially expressed genes, with 2,549 genes upregulated and 1,578 genes down-regulated in BL99-MV group than LPS group. Compared to LPS group, BL99-MV decreased FoxO6, IL-33, P53 and NFκB expression, while increased FoxO1 and Bcl2 expression. The WB showed that BL99-MV modulated NFκB, FoxO6, P53, Caspase9 and Caspase3 protein expression via reducing IL-33 expression in HT22. The findings demonstrated that IL-33 as a regulator for FoxO6/P53 signaling.