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Gut Microbiota Composition and Epigenetic Molecular Changes Connected to the Pathogenesis of Alzheimer’s Disease

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Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder, and its pathogenesis is not fully known. Although there are several hypotheses, such as neuroinflammation, tau hyperphosphorylation, amyloid-β plaques, neurofibrillary tangles, and oxidative stress, none of them completely explain the origin and progression of AD. Emerging evidence suggests that gut microbiota and epigenetics can directly influence the pathogenesis of AD via their effects on multiple pathways, including neuroinflammation, oxidative stress, and amyloid protein. Various gut microbes such as Actinobacteria, Bacteroidetes, E. coli, Firmicutes, Proteobacteria, Tenericutes, and Verrucomicrobia are known to play a crucial role in the pathogenesis of AD. These microbes and their metabolites modulate various physiological processes that contribute to AD pathogenesis, such as neuroinflammation and other inflammatory processes, amyloid deposition, cytokine storm syndrome, altered BDNF and NMDA signaling, impairing neurodevelopmental processes. Likewise, epigenetic markers associated with AD mainly include histone modifications and DNA methylation, which are under the direct control of a variety of enzymes, such as acetylases and methylases. The activity of these enzymes is dependent upon the metabolites generated by the host’s gut microbiome, suggesting the significance of epigenetics in AD pathogenesis. It is interesting to know that both gut microbiota and epigenetics are dynamic processes and show a high degree of variation according to diet, stressors, and environmental factors. The bidirectional relation between the gut microbiota and epigenetics suggests that they might work in synchrony to modulate AD representation, its pathogenesis, and progression. They both also provide numerous targets for early diagnostic biomarkers and for the development of AD therapeutics. This review discusses the gut microbiota and epigenetics connection in the pathogenesis of AD and aims to highlight vast opportunities for diagnosis and therapeutics of AD.

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Acknowledgments

The authors would like to acknowledge the Govt. College of Pharmacy, Shoolini University of Biotechnology and Management Sciences for supporting this work.

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  1. Department of Pharmaceutics, Govt. College of Pharmacy, Rohru, Himachal Pradesh, India

    Priyanka Nagu

  2. Department of Pharmacy, Shri Jagdishprasad Jhabarmal Tibrewala University, Jhunjhunu, Rajasthan, India

    Priyanka Nagu

  3. Faculty of Pharmaceutical Sciences, Shoolini University of Biotechnology and Management Sciences, Solan, Himachal Pradesh, India

    Arun Parashar

  4. Chitkara College of Pharmacy, Chitkara University, Punjab, India

    Tapan Behl

  5. Department of Pharmacology, Govt. College of Pharmacy, Rohru, Himachal Pradesh, India

    Vineet Mehta

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PN and VM designed and planned the manuscript. PN was involved in collecting literature and designing the manuscript’s first draft. TB and AP provided technical input and were involved in extensive manuscript editing. VM edited the manuscript, provided technical inputs, and finalized the draft for publication.

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Correspondence to Vineet Mehta.

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Nagu, P., Parashar, A., Behl, T. et al. Gut Microbiota Composition and Epigenetic Molecular Changes Connected to the Pathogenesis of Alzheimer’s Disease. J Mol Neurosci 71, 1436–1455 (2021). https://doi.org/10.1007/s12031-021-01829-3

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