The Possible Role of Gut Microbiome in Alzheimer Disease Pathophysiology; A Systematic Review

Background and objective: Alzheimer s disease (AD) is the most common neurodegenerative disorder which is characterized by the presence of extracellular deposition of amyloid-beta (Aβ), intraneuronal neurofibrillary tangles (NFT) and neuroinflammation. The gut microbiome is the community of commensal, symbiotic, and pathogenic microorganisms residing in the gastrointestinal tract which plays a major role in keeping host homeostasis through modulation of immunity, nutrition, and inflammation. Recent studies suggest that the gut microbiome modulates brain function and behavior via gut-brain axis, a complex and bidirectional network between gut and CNS, but the mechanism is unknown, so in this study we aimed to investigate the role of gut microbiota on AD pathophysiology. Method: An electronic search was performed in PubMed, Google Scholar and SCOPUS databases by keywords including Alzheimer s disease, microbiota, dementia, and gut microbiome. The extracted papers were studied based on inclusion criteria, and 13 articles from all obtained studies were selected in order to consider in the current study. Findings: The results of this study reveal that changes in gut microbial content and heterogeneity induced by diet, stress, pathogen infections, and using antibiotics affect Aβ accumulation and inflammatory processes and therefore associates with the pathogenesis of AD. The disruption of gut microbiota increases the intestinal permeability therefore the bacterial lipopolysaccharide (LPS) will find a way to the bloodstream, impairs blood brain barrier(BBB) and cause neuroinflammation. LPS increases hippocampal Aβ deposition and cognitive dysfunction. Gut microbiota disruption induces amyloidosis through increasing blood-to brain influx, decreasing brain-to-blood efflux and the neuronal Aβ production. Some studies reported the changes in metabolites and signaling pathways including vitamins and omega 3 polyunsaturated fatty acids (ω-3 PUFA) which are necessary for brain health, serotonin synthesis and the function of GABAergic system, the expression level of neurotoxin β-N-methylamino-L-alanine (BMAA), glutamate receptor N-methyl-D-aspartate (NMDA) and brain derived neurotrophic factor (BDNF) triggering NFT and Aβ deposits in the brain due to shifts in gut microbiota composition and therefore, increasing the risk of AD. Conclusion: In recent years the role of gut microbiota in the pathogenesis of many diseases particularly neurodegenerative diseases has attracted a lot of attention. However, the exact mechanism by which got microbiome affects brain function remains unclear. Modulation of gut microbiome composition by personalized diet interventions or using probiotics would become a new era of research in future works and will open a new window toward prevention and early treatment of neurodegenerative diseases.

کلیدواژه ها:

Alzheimer s disease ، dementia ، microbiota ، gut microbiome