The Gut Microbiome as Insight into Alzheimer’s Disease

by | Nov 9, 2020 | Alzheimer's Disease, I. Issues, Physical Therapy / Medicine and Rehabilitation | 0 comments

Cartoon image of gut and brain with bidirectional arrow between the two.

Alzheimer’s disease (AD) and other related dementias are predicted to be the greatest challenge facing healthcare and medical systems across the world. In fact, America’s total annual payments to provide care to afflicted individuals are projected to increase from 405 billion dollars in 2020 to over 1.1 trillion dollars in 2050 (1). Over recent years, AD has been added to the growing lists of diseases associated with gut microbial alterations and ultimately the brain-gut axis (3). Current research into the brain-gut axis not only provides greater insight into the pathophysiology of the disease, but also provides promise for therapeutic interventions and preventative measures.

Alzheimer’s and other dementias are characterized by progressive decline in cognitive domains which causes loss of ability to perform common activities of daily living; key features of AD are amyloid beta plaques and neurofibrillary tangles of hyperphosphorylated tau protein that trigger neuroinflammation, often leading to synapse loss and neuronal death within the brain (2). 

Studies have also found that AD is affected by gut health. Dysbiosis, or imbalance of microbes in the intestine, is known to affect the brain-gut barrier (2,4).  This brain-gut access describes the constant bidirectional communication between the central nervous system and gastrointestinal tract through the gut immune system, neuroendocrine system, neural networks, neurotransmitters, neural regulators, and the body’s physiological barriers (2,8). AD patients have increased gut inflammation (2,4), gut barrier dysfunction (2), and decreased gut microbial richness and diversity (3). Vogt et al. observed correlations between levels of differentially abundant gut microbiota and cerebrospinal fluid biomarkers of AD, supporting the link between the gut microbiota and AD pathology (3). Interestingly, the gut microbiota is a source of amyloid, which helps gut bacterial cells bind and resist destruction by immune factors (2). The gut-formed amyloid, while not identical, is similar in tertiary structure to the brain-formed amyloid. Research suggests that “cross seeding,” where the gut amyloidogenic protein causes other amyloid proteins to adopt their pathogenic beta sheet structure, may induce the amyloid plaques seen in AD (2,3). Bacterial lipopolysaccharides, created in the gut, have also been detected in hippocampus and neocortex brain lysates in AD patients. This finding is important because lipopolysaccharides colocalize with the amyloid plaques around blood vessels and work to activate a neuroinflammatory response, seen in many AD patients (2,9). Additionally, the gut microbiota can alter levels of neurotransmitters, protein and receptors involved in synaptic plasticity, and production of other neuroprotective molecules such as fatty acids and antioxidants (4).

The etiology of AD is multifactorial, and while there are no current treatments for AD, understanding the brain-gut axis is crucial for determining how pharmacology, lifestyle, and other risk factors can affect the course of the disease. Since the gut microbiota plays an important role in AD, substances such as antibiotic agents can positively or negatively affect the disease and must be carefully evaluated before use as therapeutic agents (4). Likewise, probiotics, prebiotics, and other dietary regimens may have the potential to create beneficial effects. With a greater understanding of how the gut and brain influence each other, we work towards a greater understanding of and response to AD.

Sources:

  1. Alzheimers-facts-and-figures.pdf. Retrieved September 6, 2020, from https://www.alz.org/media/Documents/alzheimers-facts-and-figures.pdf
  2. Kowalski, K., & Mulak, A. (2019). Brain-Gut-Microbiota Axis in Alzheimer’s Disease. Journal of Neurogastroenterology and Motility, 25(1), 48. https://doi.org/10.5056/jnm18087
  3. Vogt, N. M., Kerby, R. L., Dill-McFarland, K. A., Harding, S. J., Merluzzi, A. P., Johnson, S. C., Carlsson, C. M., Asthana, S., Zetterberg, H., Blennow, K., Bendlin, B. B., & Rey, F. E. (2017). Gut microbiome alterations in Alzheimer’s disease. Scientific Reports, 7. https://doi.org/10.1038/s41598-017-13601-y
  4. Angelucci, F., Cechova, K., Amlerova, J., & Hort, J. (2019). Antibiotics, gut microbiota, and Alzheimer’s disease. Journal of Neuroinflammation, 16. https://doi.org/10.1186/s12974-019-1494-4
  5. Weller, J., & Budson, A. (2018). Current understanding of Alzheimer’s disease diagnosis and treatment. F1000Research, 7. https://doi.org/10.12688/f1000research.14506.1
  6. Mendiola-Precoma, J., Berumen, L. C., Padilla, K., & Garcia-Alcocer, G. (2016). Therapies for Prevention and Treatment of Alzheimer’s Disease. BioMed Research International, 2016. https://doi.org/10.1155/2016/2589276
  7. Rusek, M., Pluta, R., Ułamek-Kozioł, M., & Czuczwar, S. J. (2019). Ketogenic Diet in Alzheimer’s Disease. International Journal of Molecular Sciences, 20(16). https://doi.org/10.3390/ijms20163892
  8. Wang, H.-X., & Wang, Y.-P. (2016). Gut Microbiota-brain Axis. Chinese Medical Journal, 129(19), 2373–2380. https://doi.org/10.4103/0366-6999.190667
  9. Zhan, X., Stamova, B., Jin, L.-W., DeCarli, C., Phinney, B., & Sharp, F. R. (2016). Gram-negative bacterial molecules associate with Alzheimer disease pathology. Neurology, 87(22), 2324–2332. https://doi.org/10.1212/WNL.0000000000003391

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