A Novel Probiotic Limosilactobacillus fermentum IOB802 and Its Postbiotic Alleviate Cognitive Impairment Induced by Scopolamine in Mice.

Cognitive impairment is acknowledged as an early stage between normal aging and Alzheimer's disease, emphasizing the need for prompt intervention. There is growing evidence that the gut-brain axis plays a role in regulating cognitive function, indicating that probiotics and their derivatives may impact cognitive functions through the brain-gut axis. In this study, we isolated and identified a novel bacterial strain Limosilactobacillus fermentum IOB802 (IOB802) from traditionally fermented pickles. This strain showed promising probiotic properties, and its postbiotic was also prepared. Both the probiotic IOB802 and its postbiotic preparation significantly improved memory and learning abilities by using a mouse model with cognitive impairment induced by scopolamine. In comparison to the scopolamine group, IOB802 and IOB802 postbiotic administration decreased acetylcholinesterase activity by 59.2% and 29.51%, increased antioxidant enzyme activity by 44.45% and 29.43%, and lowered lipid peroxidation by 44.19% and 32.53%, respectively. Moreover, IOB802 postbiotic notably boosted acetylcholine levels by 72.08%. In addition, the treatments preserved the integrity of neurons in specific regions of the hippocampus, as shown by histological analysis. The IOB802 postbiotic increased the expression of neurotrophic factors BDNF and NGF by 1.36- and 1.73-fold, while reducing the expression of inflammatory cytokines TNF-α, IL-6, and IL-1β by 2.05-, 1.85-, and 2.46-fold, respectively. Compared to the scopolamine group, IL-6 and IL-1β expression decreased by 1.32- and 2.37-fold in the IOB802 group. Additionally, IOB802, especially its postbiotic, was found to restore disrupted intestinal flora caused by scopolamine. These findings suggest that IOB802 and its postbiotic can improve cognitive function through enhancing cholinergic activity, reducing oxidative stress, providing neuroprotection, and restoring gut microbiota composition. Postbiotics, in particular, may represent a promising alternative to live probiotics for supporting cognitive health.