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.
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The original contributions presented in the study are included in the article and its supplementary information file. Further inquiries can be directed to the corresponding author.
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This work was supported by National University of Sciences and Technology (NUST), Islamabad, Pakistan. The funding sources had no involvement in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.
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SZ, substantial contribution to conception and design of the study and finalization of the manuscript; MH, all experimental work, data analysis, interpretation, and drafting the article.
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The study was reviewed and approved by Internal Review Board, NUST (IRB no. 09–2022-ASAB-01/01). All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
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Hamid, M., Zahid, S. Ameliorative effects of probiotics in AlCl3-induced mouse model of Alzheimer’s disease. Appl Microbiol Biotechnol 107, 5803–5812 (2023). https://doi.org/10.1007/s00253-023-12686-y
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DOI: https://doi.org/10.1007/s00253-023-12686-y