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Title: The Gut Microbiome and Alzheimer's Disease: A Growing Relationship
Authors: Bou Zerdan, Maroun
Hebbo, Elsa
Hijazi, Ali
El Gemayel, Maria
Nasr, Janane
Nasr, Dayana
Yaghi, Marita
Bouferraa, Youssef
Nagarajan, Arun
Affiliations: Faculty of Medicine 
Keywords: Alzheimer’s disease
Gut microbiome
Issue Date: 2022-12-27
Part of: Current Alzheimer Research
Volume: 19
Issue: 12
Start page: 808
End page: 818
Evidence that the gut microbiota plays a key role in the pathogenesis of Alzheimer's disease is already un-ravelling. The microbiota-gut-brain axis is a bidirectional communication system that is not fully understood but includes neural, immune, endocrine, and metabolic pathways. The progression of Alzheimer's disease is supported by mechanisms related to the imbalance in the gut microbiota and the development of amyloid plaques in the brain, which are at the origin of Alzheimer's disease. Alterations in the composition of the gut microbiome led to dysregulation in the pathways governing this system. This leads to neurodegeneration through neuroinflammation and neurotransmitter dysregulation. Neurodegeneration and disruption of the blood-brain barrier are frontiers at the origin of Alzheimer's disease. Furthermore, bacteria populating the gut microbiota can secrete large amounts of amyloid proteins and lipopolysaccharides, which modulate signaling pathways and alter the production of proinflammatory cytokines associated with the pathogenesis of Alz-heimer's disease. Importantly, through molecular mimicry, bacterial amyloids may elicit cross-seeding of misfolding and induce microglial priming at different levels of the brain-gut-microbiota axis. The potential mechanisms of amyloid spreading include neuron-to-neuron or distal neuron spreading, direct blood-brain barrier crossing, or via other cells such as astrocytes, fibroblasts, microglia, and immune system cells. Gut microbiota metabolites, including short-chain fatty acids, pro-inflammatory factors, and neurotransmitters may also affect AD pathogenesis and associated cognitive decline. The purpose of this review is to summarize and discuss the current findings that may elucidate the role of gut microbiota in the development of Alzheimer's disease. Understanding the underlying mechanisms may provide new insights into novel therapeutic strategies for Alzheimer's disease, such as probiotics and targeted oligosaccharides.
DOI: 10.2174/1567205020666221227090125
Type: Journal Article
Appears in Collections:Faculty of Medicine

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