Probiotics Lactobacillus acidophilus LA4 and Lacticaseibacillus paracasei F5 Alleviate Cognitive Dysfunction in Alzheimer's Disease Models: A Dual-Screening Study in Drosophila and Mice.

2026-01-24
Foods (Basel, Switzerland) 15(3)

PubMed: 41683016
DOI: 10.3390/foods15030429

Study Design

Population: transgenic Drosophila to a D-galactose/AlCl3-induced murine model; In AD mice
Methods: Through a staged screening from transgenic Drosophila to a D-galactose/AlCl3-induced murine model, Lactobacillus acidophilus LA4 and Lacticaseibacillus paracasei F5 were prioritized

Identifying probiotics that modulate the gut-brain axis is vital for non-pharmacological Alzheimer's disease (AD) therapy. Through a staged screening from transgenic Drosophila to a D-galactose/AlCl₃-induced murine model, Lactobacillus acidophilus LA4 and Lacticaseibacillus paracasei F5 were prioritized for their ability to improve climbing indices and reduce Aβ deposition and AChE activity. In AD mice, LA4 and F5 significantly ameliorated cognitive deficits and anxiety-like behaviors. Mechanistically, both strains reduced hippocampal Aβ_1-42 and p-Tau levels, inhibited AChE, suppressed pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), and enhanced antioxidant enzymes (SOD, GSH-Px). 16S rRNA analysis revealed restored Firmicutes/Bacteroidetes ratios and enrichment of SCFA-producers (Muribaculaceae, Dubosiella). Metabolomics highlighted remodeled purine and arginine pathways, with strain-specific effects on primary bile acid biosynthesis/sphingolipid metabolism (LA4) and butanoate metabolism/nicotinate and nicotinamide metabolism (F5). Consequently, LA4 and F5 alleviate AD pathology by restructuring microbial and metabolic profiles, thereby mitigating neuroinflammation and oxidative stress. These findings confirm the potential of specific probiotics as functional food ingredients for the prevention and adjuvant treatment of neurodegenerative diseases.

Research Insights

Supplement	Dose	Health Outcome	Effect Type	Effect Size	Source
Lactobacillus rhamnosus Lr-32	—	Improved Cognitive Function	Beneficial	Large	View source LA4 and F5 significantly ameliorated cognitive deficits and anxiety-like behaviors... Consequently, LA4 and F5 alleviate AD pathology by restructuring microbial and metabolic profiles, thereby mitigating neuroinflammation and oxidative stress.