Abstract
Chronic stress disrupts gut microbiota homeostasis, contributing to anxiety and depression. This study explored the effects of Limosilactobacillus reuteri fermented brown rice (FBR) on anxiety using an ICR mouse chronic mild stress (CMS) model. Anxiety was assessed through body weight, corticosterone levels, neurotransmitter profiles, and behavioral tests. A four-week FBR regimen reduced corticosterone, restored neurotransmitters like gamma-aminobutyric acid (GABA) and serotonin, and improved anxiety-related behaviors. Metagenomic (16S rRNA) and metabolomic analyses revealed enhanced amino acid metabolism, energy metabolism, and short-chain fatty acid (SCFA) production in FBR-treated mice. FBR-enriched beneficial gut bacteria, aligning the microbiota profile with that of non-stressed mice. FBR also modulated GABA receptor-related gene expression, promoting relaxation. Network pharmacology identified quercetin, GABA, glutamic acid, phenylalanine, and ferulic acid as bioactive compounds with neuroprotective potential. These findings highlight FBR's potential as a gut-brain axis-targeted therapeutic for anxiety and stress-related disorders.