Gut microbiome plays a role in Alzheimer's

By Dr. Chinta SidharthanReviewed by Danielle Ellis, B.Sc.Nov 17 2022

In a recent review published in the journal Pharmacological Research, researchers in Brazil investigated the role of gut microbiota in cognition, brain function, behavior, and neurodegenerative disease pathogenesis.

Study: Relevance of gutmicrobiota in cognition, behaviour and Alzheimer’s disease. Image Credit: nobeastsofierce / Shutterstock

Background

A growing body of evidence indicates that the gut microbiome plays an essential function in gastrointestinal health and in metabolic processes such as glucose processing, immune responses, inflammation, bone health, and central and peripheral neurotransmission.

The assembly and balance of gut microbiota begin in infancy through exposure to maternal microbiomes and continues to develop throughout the individual’s life, modified by factors such as diet. In addition, recent research has highlighted the involvement of gut microbiota in brain homeostasis, with studies in neurophysiology, neurochemistry, and neuropsychiatry reporting the role of gut microbiome disruption in brain disease pathogenesis.

Changes in gut microbiota composition have been associated with a range of diseases and disorders, such as asthma, diabetes, autoimmune disorders, Parkinson’s disease, depression, autism spectrum disorders, and Alzheimer’s disease. Enriched diets that modulate gut microbiota have shown positive results in obesity and diabetes patients.

Exposure to common peptides between humans and gut microbes is thought to increase the risk of neurodegenerative diseases such as Alzheimer’s in individuals with a genetic predisposition to the disease.

Microbiota-gut-brain axis

The review discussed various studies that explored the communication between the gut and the central nervous system mediated by the gut microbiome, also known as the microbiota-gut-brain axis. Gut microbiota secretes signaling molecules and regulates the immune system, which activates the vagus nerve and affects the brain. Changes in gut microbiota can disrupt the optimal functioning of central nervous system microglia, indirectly contributing to neurodegenerative disease pathogenesis.

Studies showed that changes in gut microbiota composition, especially relating to specific Bacteroides, Lactobacillus, Clostridium, and Bifidobacterium species, affected brain function in rodent models and humans. Furthermore, experiments with mice models lacking gut microbiota showed increased cognitive, spatial, and working memory impairments compared to wild-type mice.

Furthermore, rat models with ampicillin-induced dysbiosis exhibited anxiety, memory impairment, and increased inflammation. Probiotic treatment reestablished healthy gut microbes and resulted in a reduction of cognitive and behavioral dysfunctions. The results from these studies support the potential role of the gut microbiome in the pathogenesis of diseases such as Parkinson’s and Alzheimer’s.

Secretion of neurotransmitters

The gut microbiome is indirectly involved in neuronal communication through the secretion of neurotransmitters such as serotonin and gamma-aminobutyric acid (GABA) and trophic factors such as brain-derived neurotrophic factor (BDNF), indicating a host-microbe mutualism which extends beyond gastrointestinal homeostasis.

Lactobacillus and Bifidobacterium species produce the inhibitory neurotransmitter GABA from monosodium glutamate. Dysbiosis involving bacteria from these two genera results in decreased production of GABA, leading to excitotoxicity of the central nervous system. The subsequent accumulation of glutamate also results in the down-regulation of messenger ribonucleic acid (mRNA) expression of the N-methyl-D-aspartate receptor.

Serotonin is an essential neurotransmitter in the enteric and central nervous systems and is synthesized from the amino acid tryptophan found in dietary proteins. Almost 90% of serotonin synthesis occurs in the enterochromaffin cells found in the gastrointestinal epithelium and requires a balance between the tryptophan uptake in the epithelia and the bacterial usage of the amino acid. Enterococci and Escherichia coli are thought to play a role in modulating tryptophan availability for serotonin synthesis.

Additionally, the gut microbiota is also involved in the production of protein and mRNA of the trophic factor BDNF, which is essential for the survival and functioning of neurons in the central and peripheral nervous systems.

Microbiome and Alzheimer’s disease

Alzheimer’s disease is characterized by the excessive production and aggregation of amyloid-beta (Aβ) peptides leading to extracellular insoluble plaque formation. Gut microbiota release by-products such as amyloids and lipopolysaccharides into the gut environment, the absorption of which could alter inflammatory cytokine signaling pathways, contributing to Alzheimer’s disease pathogenesis and Aβ accumulation.

Various studies with probiotics and dietary interventions have indicated increased cognitive function and decreased Aβ accumulation in Alzheimer’s patients. Studies have also suggested a correlation between amyloidosis, cognitive impairment, and gut microbiome-secreted pro-inflammatory cytokines. Furthermore, gut peptides such as leptin and ghrelin are thought to affect nervous functions such as memory and learning, and gut microbiome changes are seen to affect plasma ghrelin levels.

Conclusions

Overall, this comprehensive review discussed the role of gut microbiota in neuronal communications between the gut and the brain and reported the results from various studies that explored the association between microbiome diversity and cognitive function.

Furthermore, the authors also examined the involvement of gut microbiota in synthesizing neurotransmitters and the association between gut microbiome function and the pathogenesis of Alzheimer’s disease.

Why is the gut microbiome important?