May 8, 2021

Does the Key to Understanding Alzheimer’s Lie in the Gut?

Written by: Marina Peric, M.D.
Reviewed by: Mubashar Rehman, PHD

The human body is a home for a variety of microorganisms. Bacteria, viruses, and fungi reside on the skin, the eyes, in the upper parts of the respiratory system, lower parts of the urinary system, the vagina, and alongside the whole digestive tract – from the oral cavity to the anus. All these human body inhabitants are collectively called microbiota, and microbiota is particularly rich and varied in the gut.
These microorganisms are no parasites. The body surfaces they populate do make their warm home, but in return, they help digestion, provide vitamin K, promote the development of the immune system, and prevent harmful microorganisms from populating. Just as the microbiota can’t live without the host, the host can’t live without the microbiota – it is cooperation to mutual satisfaction.
While a normal and balanced microbiota is necessary for overall health, changes in its composition and quantity can lead to diseases and disorders. Imbalanced gut microbiota can, for example, lead to diseases related to the digestive system. But some years ago, scientists came to a groundbreaking discovery – changes in gut microbiota are associated with brain diseases!

How Is This Possible?

It is well known that the brain communicates with the gut in several ways – by nerves, different chemicals that flow through the bloodstream, etc. Moreover, a significant part of the nervous system is located in the gut. This communication goes both ways, the brain sends signals to the gut, and the gut send signals to the brain. A disruption of this so-called brain-gut axis is known to lead to disorders such as irritable bowel syndrome (IBS).

Being an inseparable constituent of the gut, microorganisms also take part in this communication. The chemicals they produce influence the gut, the brain, and their whole signaling pathway. This is why the mentioned axis had to be renamed to the brain-gut-microbiota axis.

This gave rise to the idea that changes in microbiota could contribute to the development of brain diseases. This became a hot topic in science in the past five years, and many studies examining this hypothesis were successfully conducted and published. Most of them proved the hypothesis – changes in microbiota were associated with Alzheimer’s! A 2020 research by Zhenhuang and colleagues went further and proved that correlations exist not only with Alzheimer’s but also with schizophrenia and depression.

Mysterious Alzheimer’s

Alzheimer’s disease is the most common cause of dementia – in 2017, an estimated 40 million people worldwide suffered from it. The number of people who are indirectly affected is even bigger, as the disease is a great burden for the families, health system, caregivers, and society as a whole. The number of people with Alzheimer’s tends to grow, and unless something is done to prevent it, the number of people affected will multiply in the next decades.

Although a myriad of studies has been done, the cause of the disease and the mechanism of its development are still not clear. The treating options are also quite limited.

The key change in the development of the disease is the accumulation of a substance known as amyloid around brain cells. Amyloid triggers the brain’s immune cells, called microglia, and this leads to an inflammatory reaction. At first, the inflammation clears the amyloid and protects the brain. With aging, the immune system becomes less efficient, the inflammatory reaction becomes chronic, and the amyloid deposits more and more. The inflammation also damages the barrier between neurons and the bloodstream (the blood-brain barrier), and toxic substances from blood can easily pass into the brain tissue. Changes happen inside the neurons too. A substance called tau protein deposits within them and hinders their activity. Combined, all of this leads to losing connections between neurons and their death.

Recently, this hypothesis has been put into question, because amyloid deposits can sometimes be observed in older people who don’t have clinical signs of dementia. On the other hand, there are patients with Alzheimer’s without this type of brain change. Thus, there is a need for a more complete theory.

Are Gut Bacteria The Missing Piece? 

In the light of the brain-gut-microbiota axis, researchers have started to question whether Alzheimer’s could have an infectious background. It wasn’t long before changes in the gut microbiota were associated with the development of the disease.

There are several mechanisms through which bacteria from the gut can affect the brain. Changes in microbiota composition can cause a dysregulation of the immune system. Bacterial products can be found in the blood, and while some of them protect the body from inflammation, others support it. This contributes to a chronic inflammatory process in the brain, which is thought to be crucial for the development of Alzheimer’s disease.

In patients with Alzheimer’s, the microbiota has a reduced diversity and an altered composition, with a deficit of some bacteria and a surplus of others. Certain bacterial products found in the blood of people suffering from Alzheimer’s were associated with increased deposition of amyloid in the brain. Some of these products, such as lipopolysaccharides and some short-chain fatty acids which stimulate inflammation in the brain, are found in higher quantities in those with Alzheimer’s. At the same time, a relative number of ''good'' bacteria, which produce anti-inflammatory fatty acids, is decreased in these patients.

Hope for the Future

This discovery opens a new door to a more effective treatment of Alzheimer’s. Replacing the ‘’bad’’ bacteria in the gut with the ‘’good’’ ones could be one potential approach. Altering the gut microbiota through changes in lifestyle and diet is another one.

The main reason why there’s no cure for Alzheimer’s is that the knowledge about the nature of the disease is still insufficient. As more becomes known about the mechanisms and signaling pathways between the gut bacteria and the brain, it will become possible to develop therapeutics which would target specific cells and molecules involved in the disease development. Therapy directed towards the regulation of gut microbiota could be the future of managing Alzheimer’s.

Preclinical and clinical studies of such potential drugs are already being conducted worldwide. The results vary, and the obstacles are numerous, but it is probably only a matter of time when an appropriate treatment plan will be established. This new and targeted therapeutic approach promises a brighter future for millions of people worldwide.

References

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  2. Cryan JF, O'Riordan KJ, Cowan CSM, et al. The Microbiota-Gut-Brain Axis. Physiol Rev. 2019;99(4):1877-2013.
  3. Marizzoni M, Cattaneo A, Mirabelli P, et al. Short-Chain Fatty Acids and Lipopolysaccharide as Mediators Between Gut Dysbiosis and Amyloid Pathology in Alzheimer’s Disease. J AlzheimersDis. 2020;78(2):683.
  4. Angelucci F, Cechova K, Amlerova J, Hort J. Antibiotics, gut microbiota, and Alzheimer's disease. J Neuroinflammation. 2019;16(1):108.
  5. Kowalski K, Mulak A. Brain-Gut-Microbiota Axis in Alzheimer's Disease. J Neurogastroenterol Motil. 2019;25(1):48-60.
  6. Zhuang Z, Yang R, Wang W, Qi L, Huang T. Associations between gut microbiota and Alzheimer's disease, major depressive disorder, and schizophrenia. J Neuroinflammation. 2020;17(1):288. Published 2020 Oct 2. doi:10.1186/s12974-020-01961-8
  7. Sochocka M, Donskow-Łysoniewska K, Diniz BS, Kurpas D, Brzozowska E, Leszek J. The Gut Microbiome Alterations and Inflammation-Driven Pathogenesis of Alzheimer's Disease-a Critical Review. Mol Neurobiol. 2019;56(3):1841-1851.
  8. Zhu F, Li C, Chu F, Tian X, Zhu J. Target Dysbiosis of Gut Microbes as a Future Therapeutic Manipulation in Alzheimer's Disease. Front Aging Neurosci. 2020;12:544235.
Article written by Marina Peric, M.D.
Marina is a medical doctor from Belgrade, Serbia. She graduated with high honors in 2020 and is aspiring to become a pathologist. During her studies, she took part in several scientific researches, mostly in the pharmacology niche. She was also an assisting teacher at the Department of Histology and Embryology for 5 years (2015-2020). Marina has years of experience as a writer on health-related topics. Apart from English, she fluently speaks several languages, including Spanish, Russian, and Czech.

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