Ameliorative effects of probiotics in AlCl3-induced mouse model of Alzheimer's disease

Abstract

In recent years, gut microbiome alterations have been linked with complex underlying mechanisms of neurodegenerative disorders including Alzheimer's disease (AD). The gut microbiota modulates gut brain axis by facilitating development of hypothalamic-pituitary-adrenal axis and synthesis of neuromodulators. The study was designed to unravel the effect of combined consumption of probiotics; Lactobacillus rhamnosus GG (LGG®) and Bifidobacterium BB-12 (BB-12®) (1 × 10⁹ CFU) on AlCl₃-induced AD mouse model in comparison with potent acetylcholine esterase inhibitor drug for AD, donepezil. Mice were randomly allocated to six different study groups (n = 8). Behavioral tests were conducted to assess effect of AlCl₃ (300 mg/kg) and probiotics treatment on cognition and anxiety through Morris Water Maze (MWM), Novel Object Recognition (NOR), Elevated Plus Maze (EPM), and Y-maze. The results indicated that the combined probiotic treatment significantly (p < 0.0001) reduced anxiety-like behavior post AlCl₃ exposure. The AlCl₃ + LGG® and BB-12®-treated group showed significantly improved spatial (p < 0.0001) and recognition memory (p < 0.0001) in comparison to AlCl₃-treated group. The expression status of inflammatory cytokines (TNF-α and IL-1β) was also normalized upon treatment with LGG® and BB-12® post AlCl₃ exposure. Our findings indicated that the probiotics LGG® and BB-12® have strong potential to overcome neuroinflammatory imbalance, cognitive deficits and anxiety-like behavior, therefore can be considered as a combination therapy for AD through modulation of gut brain axis. KEY POINTS: • Bifidobacterium BB-12 and Lactobacillus rhamnosus GG were fed to AlCl₃-induced Alzheimer's disease mice. • This combination of probiotics had remarkable ameliorating effects on anxiety, neuroinflammation and cognitive deficits. • These effects may suggest that combined consumption of these probiotics instigate potential mitigation of AD associated consequences through gut brain axis modulation.

Keywords: Alzheimer’s disease; Bifidobacterium BB-12; Gut Microbiota-Brain axis; Lactobacillus rhamnosus LGG; Probiotics.