Lacticaseibacillus rhamnosus-Derived Exopolysaccharide Attenuates D-Galactose-Induced Oxidative Stress and Inflammatory Brain Injury and Modulates Gut Microbiota in a Mouse Model

This study aimed to investigate the protective effect of a novel exopolysaccharide EPSRam12, produced by Lacticaseibacillus rhamnosus Ram12, against D-galactose-induced brain injury and gut microbiota dysbiosis in mice. The findings demonstrate that EPSRam12 increases the level of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase, total antioxidant capacity, and the level of anti-inflammatory cytokine IL-10, while decreasing malonaldehyde, nitric oxide, pro-inflammatory cytokines including TNF-α, IL-1β, IL-6, MCP-1, and the mRNA expression of cyclooxygenase-2, inducible nitric oxide synthase, and the activation of nuclear factor-kappa-B in the brain tissues of D-galactose-treated mice. Further analyses reveal that EPSRam12 improves gut mucosal barrier function and increases the levels of short-chain fatty acids (SCFAs) in the intestine while restoring gut microbial diversity by enriching the abundance of SCFA-producing microbial genera Prevotella, Clostridium, Intestinimonas, and Acetatifactor while decreasing potential pathobionts including Helicobacter. These findings of antioxidative and anti-inflammatory effects in the brain and ameliorative effects on epithelial integrity, SCFAs and microbiota in the gut, provide novel insights into the effect of EPSRam12 intervention on the gut–microbiome–brain axis and should facilitate prospective understanding of microbial exopolysaccharide for improved host health.