Journal of Research in Medical and Dental Science
eISSN No. 2347-2367 pISSN No. 2347-2545

The Gut Microbiota-brain Signaling: Behavioral Abnormalities of The Gut Microbiota Underlie Alzheimer’s Disease Development and Progression. Dictatorship or Bidirectional Relationship?

Author(s): Menizibeya O Welcome

Abstract

Over the past decades, renewed research interest revealed crucial role of the gut microbiota in a range of health abnormalities including neurodevelopmental, neurodegenerative and neuropsychiatric diseases such as multiple sclerosis, autism spectrum disorders, and schizophrenia. More recently, emerging studies have shown that dysfunctions in gut microbiota can trigger the development or progression of Alzheimer’s disease (AD), which is the most common neurodegenerative disease worldwide. This paper presents a state-of-the-art review of recent data on the association between dysfunctions of the gut microbiota and AD development and progression. The review stresses on the functional integrity and expression of sealing and leaky junctional complexes of the intestinal and blood-brain barriers as well as contemporary understanding of the multiple mechanisms that underlie the association between barrier dysfunctions and β-amyloid accumulation, resulting to neuro inflammation and subsequently, progressive decrease in cognitive functions. Key determinants of cerebral amyloid accumulation and abnormal gut microbiota are also discussed. Very recent data on the interaction of the gut microbiota and local/distant immunocytes as well as calcium signaling defects that predispose to AD are also discussed. Both germ free animal models of AD and human subjects have shown that senescence, diseases, genetic and epigenetic modifications, and environmental hazards predispose to substantial reduction in composition of beneficial microbes, particularly Firmicutes and Bacteroidetes phyla and increase proinflammatory bacteria of the Proteobacteria phylum. Finally, emerging treatment with different types of psychobiotics and their limitations are highlighted. The gut microbiota-brain bidirectionality in intestinal dysfunctions and AD etiopathogensis is also discussed.

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