The Influence of the Gut Microbiota on Alzheimer's Disease: A Narrative Review

Abstract

Alzheimer's disease (AD) is a common neurodegenerative disease that tends to occur in the elderly. The main symptom is hypomnesia. More and more older people are suffering from this disease worldwide. By 2050, 152 million people worldwide are expected to have AD. It is thought that the aggregation of amyloid-beta peptides and hyper-phosphorylated tau tangles contribute to AD. The microbiotagut-brain (MGB) axis appears as a new concept. The MGB axis is a collection of microbial molecules produced in the gastrointestinal tract that influence the physiological function of the brain. In this review, we discuss how the gut microbiota (GM) and its metabolites affect AD in different ways. Dysregulation of the GM has been shown to be involved in various mechanisms involved in memory and learning functions. We review the current literature on the role of the entero-brain axis in the pathogenesis of AD and its potential role as a future therapeutic target in the treatment and/or prevention of AD.

MicroRNA (miRNA) Complexity in Alzheimer’s Disease (AD)

“…Recent evidence also indicates that resident microbes of the human gastrointestinal (GI)-tract microbiome have the potential to provide a life-long supply of microbial-derived neurotoxins including bacterial amyloids and RNA, glycolipids including lipopolysaccharide (LPS), and other potent endotoxins that appear to have significant and deleterious effects on brain miRNA complexity and which contribute to altered gene expression signaling in the AD brain [ 31 , 50 , 51 , 107 , 108 , 109 , 110 ];…”

“…The now well documented obvious importance of a global disruption in miRNA signaling in the AD-affected brain currently suggests that blocking or modulating miRNA abundance or the transcription factors such as the NF-kB p50/p65 complex that regulates miRNA generation may have some therapeutic value [ 5 , 7 , 9 , 12 , 26 , 30 , 37 ]. To this end a number of stabilized anti-miRNA (AM; antogomir), sense-RNA and anti-sense RNA-based oligonucleotide strategies have been proposed as novel therapeutic agents in the clinical management of AD [ 28 , 29 , 76 , 79 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 ]. The major problem using these types of approaches are: (i) the extreme heterogeneity of AD onset, neuropathology and disease course among individual AD patients; and (ii) the fact that miRNAs and the transcription factors that regulate them (such as the pro-inflammatory dimeric NF-kB p50/p65 complex) have both multiple and complicated off-target effects [ 28 , 37 , 39 , 112 , 113 , 114 ].…”

Gut Microbial Metabolome and Dysbiosis in Neurodegenerative Diseases: Psychobiotics and Fecal Microbiota Transplantation as a Therapeutic Approach—A Comprehensive Narrative Review

“…Recent studies have shown that these products modify the intestinal microbiota and improve cognitive functioning through the expression of neurotransmitter receptors and neuromodulators [307]. Specifically, studies in animal models showed inhibition of oxidative stress and cell apoptosis.…”

Bile acid profile associated with CSF and PET biomarkers in Alzheimer’s disease

“…Recent studies have shown that the gut microbiota can affect the development of Alzheimer's disease (AD) through various mechanisms, including neuroinflammation, amyloid-beta (Aβ) deposition, and tau protein accumulation. The gut microbiota can affect AD through several pathways, including the modulation of neurochemical and neurometabolic pathways, synthesis and secretion of neurotrophic factors, and the production of microbial molecules that influence brain function [1].…”