Introduction
Alzheimer’s disease is a progressive neurodegenerative disorder. The exact pathophysiology remains unclear despite numerous efforts taken to understand it. It can be surprisingly challenging to digest that the gut and the brain are connected. There are billions or trillions of microbes living in the gastrointestinal tract. These are generally termed the gut microbiota. Research has shown that the gut microbes and brain are connected through the gut-brain axis. The gut-brain axis refers to the physical and chemical communication between the gut and the brain.
What Is Alzheimer’s Disease?
Alzheimer’s disease is a progressive neurological disorder that hinders memory and other cognitive functions. The nerve cells and other cells in the brain are found to destroy themselves. Research shows that this could be due to the accumulation of proteins called tau and amyloids in the brain cells. The patient shows mild memory loss in the earlier stages. This progresses gradually and can reach a stage where the affected person might find it hard even to continue a conversation. The areas of the brain that control thought, memory, and language are affected in this condition. Recent studies show that the gut microbiota has an important role in the condition.
What Is Gut Microbiome?
Studies reveal the presence of trillions and billions of microbes living in the human gastrointestinal system. These include different types of bacteria, viruses, fungi, and other microorganisms. All these are collectively called the gut microbiomes. The majority of the gut microbiota comprises Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes. They play an important role in maintaining the health of the body. They are important in the process of digestion and assimilation of nutrients. In addition, they also support the immune system and make chemicals that control the brain's functioning. In general, they are responsible for maintaining a healthy body. When this disrupts, the body can become unhealthy. Alzheimer’s disease is also thought to be part of this imbalance.
The gut microbiota produces enzymes and digests many types of food that the human body otherwise finds difficult to break down. The microbes residing in the enteric mucosal linings (lining of the intestine) prevent the entry of pathogenic microorganisms into the body, acting as an immuno-neutral zone. In addition, it also influences the gastrointestinal tract and the central nervous system to work in balance. When this balance is disrupted, it results in a diseased body.
How Are Gut Microbiome and Alzheimer’s Disease Linked?
Studies show that chronic inflammation in the brain can lead to Alzheimer’s disease. Inflammatory molecules called cytokines are released as a result of inflammation. This calls for help from other cells of the immune system as well. If this continues, the chronic inflammation can cause damage or even death of neurons.
The immune cells in the brain are called microglia. They play an important role in maintaining healthy neurons, checking for invaders and cellular debris in the brain, and keeping it healthy in a healthy human being. When they find it difficult to function, or when they receive a signal from the other cells of the immune system, they are charged to engulf the invader and clear the problem. As a result, inflammatory signals are produced. As the brain ages, the activated microglia tend to stay in the activated state for a longer period of time. These exaggerated immune responses have been linked to neurodegenerative disorders like Alzheimer’s disease.
This understanding has made the experts burn their brains on the ways to reduce inflammation. They hypothesize that this would be beneficial in improving brain health. These studies proved that certain foods that are high in fiber (like whole grains, fruits, and vegetables) can be beneficial to improve brain health by reducing inflammation. The gut microbiota converts the fiber in these foods to short-chain fatty acids (SCFA). The short-chain fatty acids help in reducing inflammation and improve memory signals.
Other hypotheses on how the gut microbe helps to improve brain health can include modulation of the immune system, regulation of the blood-brain barrier, removal of the tau and amyloid protein plaques in the cells, and modification of metabolism. Studies show that people who had intestinal conditions were at a higher risk of developing Alzheimer’s disease at later stages. The alteration in the fecal microbiome was also found to be linked to Alzheimer’s disease. Eighty-five percent of people facing dementia were found to have dysbiosis in the gastrointestinal tract. People with the condition were found to have low diversity and gut microbial richness.
Several microbes were linked to the production of amyloid fibers. These fibers had the ability to cross the intestinal epithelium and reach the blood. Crossing the blood-brain barrier, they found their way to the brain, causing an accumulation in the brain cells. This was another method of how gut microbiota could cause Alzheimer’s disease. In addition, these factors produced by the gut microbes resemble the amyloids. This causes them to bind to certain receptors in the microglia. This increases the risk of Alzheimer's disease.
Oxidative stress is another causative factor in the pathophysiology of Alzheimer’s disease. A disturbance in the balance between the production of free radicals and the body’s ability to detoxify them is called oxidative stress. A dysbiosis in the gut microbiota can increase the levels of oxidative stress in the central nervous system. For example, Lactobacillus, E. coli, and Bifidobacterium convert nitrate and nitrite into nitric oxide (NO). This increases the permeability of the blood-brain barrier. This contributes to neurotoxicity, leading to Alzheimer’s disease later in life. Hydrogen is another highly dissociable bioactive gas produced by anaerobic bacteria like Enterobacteriaceae. The hydrogen production is reduced when the gut microbiota is out of balance. The neurons in the central nervous system have less hydrogen as a result. This can lead to oxidative stress, paving the way for the development of Alzheimer’s disease.
Conclusion
Alzheimer’s disease is a progressive neurodegenerative disorder. Studies show that the gut microbiota plays an important role in causing the condition. There are many mechanisms through which gut dysbiosis can cause the condition. In short, a healthy gut is important to prevent the development of Alzheimer’s disease. The use of prebiotics and probiotics in daily life can help in this. These are available as dietary supplements and in fermented food.
