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Mol Neurobiol. 2019 Mar;56(3):1841-1851. doi: 10.1007/s12035-018-1188-4. Epub 2018 Jun 23.

The Gut Microbiome Alterations and Inflammation-Driven Pathogenesis of Alzheimer's Disease-a Critical Review.

Author information

1
Laboratory of Virology, Department of Immunology of Infectious Diseases, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
2
Laboratory of Parasitology, General Karol Kaczkowski Military Institute of Hygiene and Epidemiology, Warsaw, Poland.
3
Department of Psychiatry and Behavioral Sciences, and The Consortium on Aging, The University of Texas Health Science Center at Houston, Houston, TX, USA.
4
Department of Family Medicine, Wroclaw Medical University, Wroclaw, Poland.
5
Laboratory of Medical Microbiology, Department of Immunology of Infectious Diseases, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
6
Department of Psychiatry, Wroclaw Medical University, Wroclaw, Poland. jerzy.leszek@umed.wroc.pl.

Abstract

One of the most important scientific discoveries of recent years was the disclosure that the intestinal microflora takes part in bidirectional communication between the gut and the brain. Scientists suggest that human gut microflora may even act as the "second brain" and be responsible for neurodegenerative disorders like Alzheimer's disease (AD). Although human-associated microbial communities are generally stable, they can be altered by common human actions and experiences. Enteric bacteria, commensal, and pathogenic microorganisms, may have a major impact on immune system, brain development, and behavior, as they are able to produce several neurotransmitters and neuromodulators like serotonin, kynurenine, catecholamine, etc., as well as amyloids. However, brain destructive mechanisms, that can lead to dementia and AD, start with the intestinal microbiome dysbiosis, development of local and systemic inflammation, and dysregulation of the gut-brain axis. Increased permeability of the gut epithelial barrier results in invasion of different bacteria, viruses, and their neuroactive products that support neuroinflammatory reactions in the brain. It seems that, inflammatory-infectious hypothesis of AD, with the great role of the gut microbiome, starts to gently push into the shadow the amyloid cascade hypothesis that has dominated for decades. It is strongly postulated that AD may begin in the gut, and is closely related to the imbalance of gut microbiota. This is promising area for therapeutic intervention. Modulation of gut microbiota through personalized diet or beneficial microbiota intervention, alter microbial partners and their products including amyloid protein, will probably become a new treatment for AD.

KEYWORDS:

Alzheimer’s disease; Gut microbiome; Microbial amyloid; Neuroinflammation; Therapeutic intervention

PMID:
29936690
PMCID:
PMC6394610
DOI:
10.1007/s12035-018-1188-4
[Indexed for MEDLINE]
Free PMC Article

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