Replenishing the Alzheimer’s disease–associated depleted species Lactobacillus gasseri improves gut microbiota composition and reduces amyloid-β pathology

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive memory loss and cognitive decline. Although the abnormal metabolism of amyloid-β (Aβ) remains a central hypothesis of AD pathogenesis, effective therapeutic strategies are still lacking. Growing evidence suggests that the gut microbiota and its metabolites influence brain function, and that gut dysbiosis can disrupt metabolic homeostasis, increase intestinal permeability, and promote the translocation of pathogens or inflammatory signals that impair cognition. In this study, we observed that APP ^{NL−G−F/NL−G−F} transgenic mice exhibited a marked reduction in the relative abundance of Lactobacillus gasseri compared with wild-type controls. Oral administration of L. gasseri for 8 weeks significantly improved short-term memory performance in the transgenic mice. Furthermore, L. gasseri supplementation reshaped the gut microbial composition and reduced Aβ accumulation in the intestine, colon, and hippocampus. Taken together, these findings suggest that restoring L. gasseri abundance may represent a promising probiotic-based strategy for improving intestinal homeostasis and mitigating neurodegenerative processes in AD.