Neuroprotective Effects ofClostridium butyricumagainst Vascular Dementia in Mice via Metabolic Butyrate

Abstract

Probiotics actively participate in neuropsychiatric disorders. However, the role of gut microbiota in brain disorders and vascular dementia (VaD) remains unclear. We used a mouse model of VaD induced by a permanent right unilateral common carotid arteries occlusion (rUCCAO) to investigate the neuroprotective effects and possible underlying mechanisms ofClostridium butyricum. Following rUCCAO,C. butyricumwas intragastrically administered for 6 successive weeks. Cognitive function was estimated. Morphological examination was performed by electron microscopy and hematoxylin-eosin (H&E) staining. The BDNF-PI3K/Akt pathway-related proteins were assessed by western blot and immunohistochemistry. The diversity of gut microbiota and the levels of butyrate in the feces and the brains were determined. The results showed thatC. butyricumsignificantly attenuated the cognitive dysfunction and histopathological changes in VaD mice.C. butyricumnot only increased the levels of BDNF and Bcl-2 and decreased level of Bax but also induced Akt phosphorylation (p-Akt) and ultimately reduced neuronal apoptosis. Moreover,C. butyricumcould regulate the gut microbiota and restore the butyrate content in the feces and the brains. These results suggest thatC. butyricummight be effective in the treatment of VaD by regulating the gut-brain axis and that it can be considered a new therapeutic strategy against VaD.