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The lipopolysaccharide (LPS) accumulate amyloid beta (A\u03b2) and lead to HNF. The Bifidobacterium lactis (BL) 99 have anti-inflammatory ability. However, whether BL99-derived microbiota-derived vesicles (MV) could alleviate LPS-induced HNF remains unclear. Methods: To investigate, we used ultrafiltration with ultracentrifuge to extract BL99-derived-MV (BL99-MV). We used hippocampal neuronal HT22 cells (HT22) to establish the LPS-induced HNF model, and explored whether BL99-MV alleviate LPS-induced HNF. Results: The confocal microscopy showed that BL99-MV were taken up by HT22 and reduced the oxidative stress (ROS) level. The PCR showed that BL99-MV up-regulate IL-10 level, and down-regulate TNF-\u03b1, IL-1\u03b2, and IL-6. Transcriptomic analysis revealed 4127 differentially expressed genes, with 2549 genes upregulated and 1578 genes downregulated in the BL99-MV group compared to the LPS group. Compared to the LPS group, BL99-MV decreased FoxO6, IL-33, P53, and NF\u03baB expression, but increased FoxO1 and Bcl2 expression. The WB showed that BL99-MV modulated NF\u03baB, FoxO6, P53, Caspase9, and Caspase3 protein expression by reducing IL-33 expression in HT22. The findings demonstrated IL-33 as a regulator for FoxO6\/P53 signaling. Conclusions: Here, we hypothesized that BL99-MV alleviated LPS-induced HNF to promote HT22 survival and synaptic development by regulating FoxO6\/P53 signaling by targeting IL-33.<\/jats:p>","DOI":"10.3390\/nu16213586","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T11:31:57Z","timestamp":1729596717000},"page":"3586","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Bifidobacterium lactis-Derived Vesicles Attenuate Hippocampal Neuroinflammation by Targeting IL-33 to Regulate FoxO6\/P53 Signaling"],"prefix":"10.3390","volume":"16","author":[{"given":"Xiaoyu","family":"Du","sequence":"first","affiliation":[{"name":"School of Food and Health, Beijing Technology and Business University, Beijing 100048, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1175-4636","authenticated-orcid":false,"given":"Ming","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Food and Health, Beijing Technology and Business University, Beijing 100048, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaozhong","family":"Zeng","sequence":"additional","affiliation":[{"name":"National Center of Technology Innovation for Dairy, Hohhot 010110, China"},{"name":"Inner Mongolia Yili Industrial Group Co., Ltd., Hohhot 010100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4818-9079","authenticated-orcid":false,"given":"Bing","family":"Fang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanglian","family":"Lan","sequence":"additional","affiliation":[{"name":"National Center of Technology Innovation for Dairy, Hohhot 010110, China"},{"name":"Inner Mongolia Yili Industrial Group Co., Ltd., Hohhot 010100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weilian","family":"Hung","sequence":"additional","affiliation":[{"name":"National Center of Technology Innovation for Dairy, Hohhot 010110, China"},{"name":"Inner Mongolia Yili Industrial Group Co., Ltd., Hohhot 010100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1327-4003","authenticated-orcid":false,"given":"Haina","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Food and Health, Beijing Technology and Business University, Beijing 100048, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3491","DOI":"10.1111\/ene.14913","article-title":"Encephalitis as a neurological complication of COVID-19: A systematic review and meta-analysis of incidence, outcomes, and predictors","volume":"28","author":"Siow","year":"2021","journal-title":"Eur. 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