Submit Manuscript  

Article Details


The Gut-Brain Axis, Including the Microbiome, Leaky Gut and Bacterial Translocation: Mechanisms and Pathophysiological Role in Alzheimer’s Disease

[ Vol. 22 , Issue. 40 ]

Author(s):

Cristiano A. Köhler, Michael Maes, Anastasiya Slyepchenko, Michael Berk, Marco Solmi, Krista L. Lanctôt and André F. Carvalho   Pages 6152 - 6166 ( 15 )

Abstract:


Alzheimer’s disease (AD), the most common form of dementia, is a progressive disorder manifested by gradual memory loss and subsequent impairment in mental and behavioral functions. Though the primary risk factor for AD is advancing age, other factors such as diabetes mellitus, hyperlipidemia, obesity, vascular factors and depression play a role in its pathogenesis. The human gastrointestinal tract has a diverse commensal microbial population, which has bidirectional interactions with the human host that are symbiotic in health, and in addition to nutrition, digestion, plays major roles in inflammation and immunity. The most prevalent hypothesis for AD is the amyloid hypothesis, which states that changes in the proteolytic processing of the amyloid precursor protein leads to the accumulation of the amyloid beta (Aβ) peptide. Aβ then triggers an immune response that drives neuroinflammation and neurodegeneration in AD. The specific role of gut microbiota in modulating neuro-immune functions well beyond the gastrointestinal tract may constitute an important influence on the process of neurodegeneration. We first review the main mechanisms involved in AD physiopathology. Then, we review the alterations in gut microbiota and gut-brain axis that might be relevant to mediate or otherwise affect AD pathogenesis, especially those associated with aging. We finally summarize possible mechanisms that could mediate the involvement of gut-brain axis in AD physiopathology, and propose an integrative model.

Keywords:

Alzheimer’s disease, amyloid beta, gut, microbiota, aging, dementia, gut-brain axis, psychiatry, neurology

Affiliation:

Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Rua Prof. Costa Mendes, 1608, 4º andar, 60430-040, Fortaleza, CE, Brazil.



Read Full-Text article