The Gut Flora and Alzheimer’s Disease (AD)
The hallmark of Alzheimer’s disease (AD) is associated with the accumulation of “senile” plaques that are composed of amyloid-beta (Aβ) protein that surround neurons in affected regions.
This accumulation results in loss of neurons in the hippocampus and cerebral cortex, leading to progressive cognitive decline such as memory defects.
A connection between the brain and the gastrointestinal tract has been suggested due to the significant influence of the gastrointestinal flora (microbiome or microbiota) over the brain-gut axis [1] [2].
1. What Is the Role of Gut Flora in Alzheimer’s Disease?
The gastrointestinal tract is full of harmless bacteria that positively affect our health and contribute to our body’s natural processes. However, unbalance of the gut flora (Dysbiosis) can lead to significant pathological changes that can affect our immune system and brain functions.
This unbalance is due to several reasons such as a dietary change, accidental chemical consumption (unwashed pesticides on fruit and vegetables), alcohol consumption, inflammation, and excessive antibiotics’ medication.
2- What Is the Role of Dietary Changes in Alzheimer’s disease (AD)?
To reduce the risk of losing neurons in the hippocampus and cerebral cortex, responsible for the progressive cognitive decline (memory loss), it is necessary to consume food that is rich in compounds that promote and maintain the survival of neurons and their connectivity to each other.
- Glutathione
Glutathione is an antioxidant that prevents damage to neurons that are caused by reactive oxidative stress, such as free radicals, and heavy metals.
Substances that are metabolized in the liver and excreted in the bile require conjugation with glutathione to facilitate their absorption by the gut circulation [3].
Glutathione is mainly found in foods such as beef, poultry, eggs, milk, avocados, strawberries, oranges, blueberries, watermelon, peaches, and grapefruit.
- Polyphenols
Polyphenols are organic compounds that include flavonoids, such as quercetin, and epigallocatechin gallate. Quercetin is an inhibitor of the enzyme, BACE-1 (beta-amyloid precursor protein–cleaving enzyme 1) that has a role in the formation of beta-amyloid plaques [4].
In the gut, the microbiota transforms polyphenols into neuroprotective polyphenols that protect neurons during Alzheimer’s disease [4].
Foods that are rich in polyphenols include cocoa products, blueberries, various spices, dried herbs, flaxseed, nuts (chestnut, hazelnut), olive and artichoke heads.
- Curcumin (Turmeric)
Curcumin is a bioactive polyphenolic extract of turmeric that is used as a spice, food additive, and herbal medicine.
Curcumin has antioxidant, anti-inflammatory, metal binding, and neuroprotective activities that improve the cognitive functions in patients with Alzheimer’s disease (AD) [5].
In the gut, curcumin was suggested to favor beneficial bacteria by increasing the abundance of Bifidobacterium and Lactobacilli and reducing pathogenic bacteria such as Prevotellaceae, Enterobacteria, Enterococci, and Coriobacteriia that can affect brain health [6].
Vitamin B6 is an essential coenzyme involved in the metabolism of glucose, fat, and proteins [7]. Vitamin B6 is also involved in lowering the level of homocysteine (made from methionine) in the blood by converting it into cysteine.
An increased homocysteine level (hyperhomocysteinemia) can result in blood vessels damage, including vessels in the brain which can affect nutrients supply to neurons leading to their death by starvation [8].
In the gut, Vitamin B6 (microbial vitamin B6) can be produced by bacteria such as Bacteroidetes and Proteobacteria, where it also contributes to the gut immunity to ensure the proper function of the gut in nutrients absorption [9].
Vitamin B6 is mainly found in meat products such as Beef, pork, chicken, and fish.
Vitamin B12 is a coenzyme involved in fatty acids and protein metabolisms, DNA synthesis, and maturation of red blood cells.
It is also necessary for the production of myelin, a protein covering neurons, and necessary for the nervous system function through its role in the transfer of nerve impulses and metabolic support of neurons [10].
Like vitamin B6, vitamin B12 also reduces homocysteine level (hyperhomocysteinemia) and prevents the damage of blood vessels, including vessels of the brain which, and therefore, can affect nutrients supply to neurons leading to their death by starvation [11].
In the gut, certain bacteria and archaea produce vitamin B12 during food fermentation.
It is naturally present in foods such as meat, liver, milk, clams, fortified breakfast cereals, and eggs.
Vitamin B9 is required for DNA synthesis and for the activation of vitamin B12, and therefore, indirectly plays an important role in protecting blood vessels from damage, including the brain blood vessels [12].
Many bacteria in the gut produce an active form of folic acid known as tetrahydrofolate (THF), including Bacteroides, firmicutes, actinobacteria, fusobacteria, and proteobacteria.
Many types of food contain vitamin B9; however, due to its instability (e.g., high heat cooking), it is being added to several food sources as a fortifier to prevent a vitamin B9 deficiency.
- Unsaturated Fatty Acids
Unsaturated Fatty Acids are parts of phospholipids that are necessary for the formation of the membranes of cells, including neurons. One of the most known unsaturated Fatty Acids is omega-3 polyunsaturated fatty acids [13].
In the gut, the microbiota regulates the availability and absorption of unsaturated fatty acids
Foods that are rich in omega-3 polyunsaturated fatty acids include salmon, sardines, and mackerel.
- Lecithin
Lecithin is a fatty substance composed of a mixture of phospholipids that are rich in choline, a necessary component of the neurotransmitter acetylcholine that is involved in memory, mood, muscle, and nervous system functions [14].
In the gut, food that contains lecithin is digested by the pancreas and mucosal enzymes to produce choline that is absorbed by the gut circulation.
Lecithin is mainly found in foods such as meat, poultry, fish, dairy products, and eggs.
- Caffeine
Caffeine is a stimulant of the central nervous system where it has effects on learning, memory, alertness, and concentration. Caffeine has antioxidant effects and may protect against cell damage, including damages to neurons, by reducing oxidative stress [15].
Beverages, such as coffee, tea, soft and energy drinks, are digested by the gut flora to generate caffeine that is absorbed by the intestine’s circulation.
The most common prebiotics are fructooligosaccharides, galactooligosaccharides, and trans-galactooligosaccharides, but other prebiotics plays important roles in health and aging such as insulin enriched-oligofructose, lactulose, and oligofructose [16].
They are indigestible carbohydrates that are fermented and broken down by probiotics to obtain survival energy, and short-chain fatty acids such as lactic acid, butyric acid, and propionic acid.
The administration of prebiotics such as non-starch polysaccharides was shown to improve the performance of working and recognition memory and cognitive functions [17].
Prebiotics are found in carrots, quinoa, radishes, onions, chicory roots, konjac roots, oats, yams, garlic, barley, wheat bran, berries, apples, asparagus, bananas, leeks, chia seeds, flax seeds, cocoa, coconut, jicama root, and dandelion greens.
The gut contains beneficial bacteria known as good bacteria, such as Lactobacillus and Bifidobacterium. These bacteria help other gut bacteria produce nutrients for the body by providing them with nutrients that are commonly known as prebiotics [18].
Probiotics are found in yogurt, lactobacillus milk, some cheeses such as Gouda, cheddar, cottage cheese, and mozzarella, pickles, sauerkraut, kefir, kimchi, tempeh, kombucha, and miso.
3- What Is the Role of Alcohol in Alzheimer’s disease (AD)?
Excessive consumption of alcohol for a long period can damage the brain and reduce the size of the brain white matter responsible for signal transmission in the brain.
It can also cause a deficiency in vitamin B1 resulting in diseases such as Korsakoff’s syndrome characterized by alterations in short-term memory [19].
4- What Is the Role of Pesticides in Alzheimer’s disease (AD)?
Pesticides are neurotoxins that can induce oxidative stress, the fibrilization of tau and alpha-synuclein (formation of amyloid fibrils), alteration in the function of mitochondria, and the loss of neurons [20].
People such as gardeners and farmers that use pesticides for their activities are at higher risks of neurodegenerative diseases such as Alzheimer’s disease (AD).
Accidental consumption of pesticides associated with unwashed pesticides on fruit and vegetables can also increase the risk of developing Alzheimer’s disease (AD).
5- What Is the Role of Excessive Antibiotic Medication in Alzheimer’s disease (AD)?
Excessive use of antibiotics can cause an imbalance in the gut flora (microbiota) and affect the function of the probiotic population necessary for the generation of essential nutrients to the function of the body organs, including the brain [21].
6- What Is the Role of Neuroinflammation in Alzheimer’s disease (AD)?
Imbalance of the gut flora (Dysbiosis) can lead to disruptions in the gastrointestinal permeability and blood-brain barrier, that are due to the secretion of amyloid and lipopolysaccharides (LPS), known to modulate the inflammatory signaling pathway leading to neuroinflammation, neuronal injury, and ultimately to neuronal death in Alzheimer’s disease (AD) [1] [22].
Conclusion
To reduce the risk of Alzheimer’s disease (AD) that could be associated with an unbalance in the Gut flora (Dysbiosis), a healthy diet and the implementation of a healthy nutritive plan throughout a life of an individual is necessary.
Intake of pre-and probiotics, vitamins (B-complex vitamins), calcium, magnesium, zinc, and beta-carotene, can help prevent dysbiosis, while the consumption of processed meat, high carbohydrates containing food, and dairy products as well as excessive use of antibiotics, may promote dysbiosis.
