id_963. INNOVATIVE NEUROPROTECTION: COMMENSAL BIFIDOBACTERIUM EXTRACELLULAR VESICLES PRESERVE BLOOD–BRAIN BARRIER FUNCTION UNDER INFLAMMATORY CONDITIONS
Agnieszka Zabłocka1, Dominika Kozakiewicz1, Natalia Małek2, Dominika Jakubczyk1, Józefa Macała1, Sabina Górska1
1 Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Laboratory of Microbiome Immunobiology, R. Weigla 12, 53-114, Wroclaw, Poland
2 Wroclaw University of Science and Technology, Department of Chemical Biology and Bioimaging, Faculty of Chemistry, Wybrzeże Wyspianskiego 27, 50-370 Wroclaw, Poland
INTRODUCTION: Age-related alterations of the gut microbiota contribute to systemic inflammation. Circulating pro-inflammatory factors may impair blood–brain barrier (BBB) integrity, promoting central nervous system inflammation, neuronal damage, and progressive cognitive decline. Although the gut–brain axis is increasingly recognised as a key regulator of brain health, the specific contribution of commensal bacteria and their secreted products remains poorly defined.
AIM(S): This study aimed to characterise bacterial extracellular vesicles (BEV) produced by Bifidobacterium animalis subsp. animalis CCDM 366 (Ba366) and to evaluate the protective effects of Ba366 and its BEV on BBB integrity.
METHOD(S): Human brain microvascular endothelial cells (HBEC-5i) were used as an in vitro BBB model. The effects of Ba366 and BEV were assessed under physiological and inflammatory conditions. Cell viability and proliferation were analysed using MTT assay and Incucyte S3 live-cell imaging. BBB integrity was evaluated by transendothelial electrical resistance and paracellular permeability assays. Transcriptomic analysis was performed to identify changes in gene expression.
RESULTS: Ba366 and BEV were non-cytotoxic to HBEC-5i cells, modulated cell proliferation, reduced paracellular permeability, and enhanced barrier integrity. Ba366 enriched genes associated with cell proliferation and hormonal and neuronal signalling, whereas BEV enriched genes involved in ion transport, neurotransmitter signalling, membrane function, and pathways regulating autophagy and cell growth.
CONCLUSIONS: Ba366 and its BEV modulate BBB integrity and function through complementary molecular mechanisms. In the context of age-associated gut microbiota dysbiosis and systemic inflammation, these findings support the potential of Ba366-derived components to preserve or restore BBB integrity and mitigate neuroinflammatory processes.
FINANCIAL SUPPORT: This work was supported by the Biocodex Microbiota Foundation.