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Dysbiosis and Alzheimer’s disease: role of probiotics, prebiotics and synbiotics

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Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by dementia and the accumulation of amyloid beta in the brain. Recently, microbial dysbiosis has been identified as one of the major factors involved in the onset and progression of AD. Imbalance in gut microbiota is known to affect central nervous system (CNS) functions through the gut-brain axis and involves inflammatory, immune, neuroendocrine and metabolic pathways. An altered gut microbiome is known to affect the gut and BBB permeability, resulting in imbalance in levels of neurotransmitters and neuroactive peptides/factors. Restoration of levels of beneficial microorganisms in the gut has demonstrated promising effects in AD in pre-clinical and clinical studies. The current review enlists the important beneficial microbial species present in the gut, the effect of their metabolites on CNS, mechanisms involved in dysbiosis related to AD and the beneficial effects of probiotics on AD. It also highlights challenges involved in large-scale manufacturing and quality control of probiotic formulations.

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Data availability

Data sharing is not applicable to this article as no new data were created or analysed in this study.

Abbreviations

AD:

Alzheimer’s disease

ROS:

reactive oxygen species

CNS:

central nervous system

GABA:

gamma amino butyric acid

SCFA:

short-chain fatty acids

COX-2:

cyclooxygenase-2

FMT:

faecal microbiota transplantation

Aβ:

β-amyloid

TLR2:

toll-like receptor-2

MAPK:

mitogen-activated protein kinase activator protein-1

FDA:

Food and Drug Administration

NMDAR:

N-methyl-D-aspartate receptor

BDNF:

brain-derived neurotropic factor

BBB:

blood-brain barrier

TGF β:

transforming growth factor beta

TNF-α:

tumour necrosis factor alpha

IL:

interleukin

HPA:

hypothalamic-pituitary-adrenal

DALYs:

disability-adjusted life years

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Acknowledgements

The authors are thankful to Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM’s NMIMS for providing the infrastructural facilities.

Funding

The authors received financial support from the Central Council for Research in Unani Medicine, Ministry of AYUSH (3-18/2021-CCRUM/Tech).

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Authors and Affiliations

  1. Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, Shri Vile Parle Kelavani Mandal’s Narsee Monjee Institute of Management Studies, Mumbai, India

    Ami Thakkar, Amisha Vora & Ginpreet Kaur

  2. Central Council for Research in Unani Medicine, Ministry of AYUSH, New Delhi, India

    Jamal Akhtar

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  1. Ami Thakkar
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  2. Amisha Vora
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  3. Ginpreet Kaur
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Contributions

Amisha Vora and Ginpreet Kaur made the draft of the review. Ami Thakkar and Amisha Vora contributed by doing literature searches and preparing a manuscript draft. Amisha Vora, Jamal Akhtar and Ginpreet Kaur revised and approved the manuscript. All authors contributed to the article and approved the submitted version. The authors confirm that no paper mill and artificial intelligence was used.

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Correspondence to Amisha Vora.

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Thakkar, A., Vora, A., Kaur, G. et al. Dysbiosis and Alzheimer’s disease: role of probiotics, prebiotics and synbiotics. Naunyn-Schmiedeberg's Arch Pharmacol 396, 2911–2923 (2023). https://doi.org/10.1007/s00210-023-02554-x

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