Selenium Nanoparticles-Enriched Lactobacillus casei ATCC 393 Prevents Cognitive Dysfunction in Mice Through Modulating Microbiota-Gut-Brain Axis

Lei Qiao, Yue Chen, Xiaofan Song, Xina Dou, Chunlan Xu The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an, People’s Republic of ChinaCorrespondence: Chunlan Xu, The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an, People’s Republic of China, Tel +86 29-88460543, Fax +86 29-88460332, Email clxu@nwpu.edu.cnPurpose: The bidirectional communication between the gut and the central nervous system mediated by gut microbiota is closely related to the occurrence and development of neurodegenerative diseases, including Alzheimer’s disease (AD). Selenium (Se) has been identified as playing a role against AD. Probiotics have beneficial effects on host brain function and behavior by modulating the microbiota-gut-brain axis. Herein, we evaluated the protective effects of Lactobacillus casei ATCC 393 (L. casei ATCC 393) and selenium nanoparticles-enriched L. casei ATCC 393 (L. casei ATCC 393-SeNPs) against D-galactose/aluminum chloride-induced AD model mice.Methods: The Morris Water Maze (MWM) test was used to assess cognitive function of mice. The morphology and histopathological changes, antioxidant capacity and immune responses in the brain and ileum were evaluated. The alterations in intestinal permeability of the mice were determined using FITC-dextran. Gut microbiota composition was assessed using 16s rRNA sequencing.Results: Thirteen weeks intervention with L. casei ATCC 393 or L. casei ATCC 393-SeNPs significantly improved cognitive dysfunction, and minimized amyloid beta (Aβ) aggregation, hyperphosphorylation of TAU protein, and prevented neuronal death by modulating Akt/cAMP-response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway. Moreover, compared with L. casei ATCC 393, L. casei ATCC 393-SeNPs further effectively mi