Modulatory effect of porous silicon water-formulated catechin on gut microbiome in chronic unpredictable mild stress-induced dementia in a rat model

Stress-induced dysbiosis exacerbates mental health by modulating the nervous system and gut permeability. In this study, we investigate the therapeutic potential of porous silicon water-mixed catechin in alleviating chronic stress-induced dementia in rats. In a 28-day study, chronic unpredictable mild stress (CUMS)-induced rats were treated with <i>Lactobacillus acidophilus</i> (2.5 × 10^9 CFU, p.o), porous silicon water (7 mg/kg, p.o), catechin (30 mg/kg, p.o), and porous silicon water-mixed catechin (PSC) (7 mg and 30 mg/kg, p.o). The effect of porous silicon water-mixed catechin was evaluated through behavioral studies, plasma acetylcholinesterase activity, plasma glutamate, brain reactive oxygen species (ROS), brain endogenous anti-oxidant enzymes, metagenomics analysis, and histological examination of the prefrontal cortex and hippocampus. Administration of PSC significantly improved spatial learning and memory by reducing escape latency time and increased exploratory behavior in the open platform. PSC significantly inhibited acetylcholinesterase enzyme activity and restored endogenous antioxidants such as superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH) while reducing lipid peroxidation (LPO) compared to the CUMS group. In addition, PSC decreased the brain ROS levels, as determined by a fluorescence assay, and reduced plasma glutamate levels. 16S rRNA V3-V4 metagenomic analysis revealed a significant increase in microbial diversity (Shannon index: 7.52), microbial richness (Chao1 index: 1059.41), β-diversity index, and overall taxonomic abundance in treated rats. CUMS-induced morphological alterations in the hippocampus and prefrontal cortex were significantly improved following PSC administration. In the present study, Pearson correlation coefficient (r) demonstrates an association between gut microbial abundance and AChE activity. Hence, it has been concluded that PSC treatment may significantly modulate the gut microbiome and improve cognition in chronic unpredictable mild stress-induced dementia.