Prebiotics

The Second Brain and Alzheimer's

Have you ever heard your gut referred to as your second brain? Well, the reason why some scientists refer to the gut as the second brain is because the gut has its own nervous system called the enteric nervous system (ENS) complete with neuron and neurotransmitters. The central nervous system includes the brain and spinal cord. The CNS and ENS communicate with each other, however the brain tends to receive signals from the gut rather than the other way around. Importantly for us, the ENS has been shown to affect memory and learning as well as have the ability to influence Alzheimer’s disease.1

Prebiotics, the Brain and Prions

It would be beneficial to illustrate the link between the brain and the gut before talking further about prebiotics. To do that, let’s quickly talk about prions. We have previously discussed prion diseases in the chapter about different Alzheimer’s hypotheses. Prions are misfolded proteins that are considered infectious because they can cause a cascade effect which results in more and more of that same misfolded prion protein causing a disease. In mad cow disease, the prion protein is eaten and that protein migrates from the stomach to the brain where the protein propagates until the infected person is killed. The ENS is thought to play a central role in the transport of mad cow prions to the brain by shuttling the prions from the stomach to the nerves that are connected directly to the brain.2

The Microbiome and Amyloid Priming

It is common knowledge that our guts house millions of microorganisms, but what some people might not realize is that these microorganisms have been shown to have a strong influence on the health of our brains. The microbes within our bodies are our microbiome and everyone has a different composition of microbes in their gut, making their microbiome similar to a fingerprint. These microbes help with digestion, but they also influence our brains and immune system.

As you all know, amyloid beta is one of the characteristics of Alzheimer’s disease. Microbes in the gut produce other types of amyloid proteins. Amyloid proteins are proteins which clump together in a particular way forming a molecular structure called beta-sheets. An example of a bacterial amyloid protein is a protein called curli which is produced by e. Coli. Some scientists believe that the amyloid proteins produced by the microbiome can somehow prime the brain to produce amyloid-beta plaques similar to how prions can create a cascade effect of misfolded proteins. The hypothesis is that amyloid proteins in the gut microbiome cause the brain amyloid-beta proteins to form the pathogenic beta-sheet structure characteristic of amyloid beta plaques. Several studie of shown that this cross-seeding effect is possible in both in vitro experiments and in vivo experiments.3

The Microbiome and Neuroinflammation

Some bacteria has a cell wall composed of lipopolysaccharides (LPS). LPS has been found to migrate to amyloid beta plaques. It has been found that the brain concentration of LPS is higher in people with Alzheimer’s. In addition, LPS activates the immune system and causes inflammation, including neuroinflammation. Long-term chronic neuroinflammation by bacterial LPS could hinder the clearance of amyloid-beta plaques. Gut inflammation originating from the microbiome could causes the intestines to become more permeable which in turn creates more inflammation within the body.3

The mucus lining of the intestines protects your cells against pathogenic bacteria, but the mucus lining and the barrier of your gut is dependent on the type and amount of bacteria within your microbiome. A bacteria called Akkermansia muciniphila improves the gut barrier and reduces inflammation. Lactobacillus plantarum, E. coli Nissle, and Bifidobacterium infantis can also improve the gut barrier. On the other hand, pathogenic E. coli strains, Salmonella, Shigella, Helicobacter pylori, Vibrio, or Clostridium damage the gut barrier and can increase intestinal permeability. We need to keep the gut microbiome in the gut, but damage to our intestines could cause microbes to leave the gut and enter into the bloodstream causing damage throughout the body.3

Using Gut Microbes to Fight Alzheimer's

To help fight Alzheimer’s it is important for us to eat foods that promote the growth of the gut microbes we want and to inhibit the growth of microbes that are harmful. Some scientists have suggested fecal microbiota transplantation from young donors to older people. However, changing your diet to promote the growth of good microbes is undoubtedly a more practical option.3

The microbiome is relatively stable over a person’s lifetime, large changes in diet can influence the microbiome. People that moved from Thailand to the United States were shown to have a westernization of their microbiome, presumably from the westernization of their diet. Consumption of antibiotics, either by ingesting food treated with antibiotics or taking antibiotics for medical purposes, can kill off much of the microbiome. Some scientists have hypothesized that the routine consumption of antibiotics has led to the increase of many chronic diseases within industrialized countries. When the natural microbiome is killed off, harmful microbes are able to colonize the gut since they no longer have to compete with billions of other microbes.4,5,6

Diet and the Microbiome

While there is not much clarity on which exact organisms or ratio of organisms constitutes a healthy microbiome, a diet rich in fruits and vegetables with little to no meat are associated with Prevotella organisms within the gut. On the other hand, heavy meat eaters and people who tend to eat the typical western diet will have more Bacteroides. One in vivo study found that an increase in Bacteroides in the guts of mice increases amyloid beta plaques in the brain. This result has been collaborated in clinical studies. A Japanese researcher found that Bacteroides was decreased in demented patients compared to non-demented patients. Multiple human studies have noted that the diversity of microbes in the gut of Alzheimer’s patients is reduced. One difference is that Firmicutes appears to be reduced in Alzheimer’s patients and Proteobacteria seems to be increased.4,6

The diets discussed in this chapter can also alter the microbiome. For example, a gluten free and a ketogenic diet have both been shown to decrease the overall diversity of the microbiome. Some researchers recommend adding prebiotics and probiotics in order to restore the normal balanced microbiome. Probiotics are live microbes, whereas prebiotics are foods or supplements that help microbes in the gut flourish. We’ll discuss probiotics and prebiotics in more detail in the next chapter, but now we’ll discuss prebiotic foods that can benefit the microbiome.7

Prebiotics and a Healthy Microbiome

Prebiotics are critical in establishing a healthy gut microbiome. For a food to be classified as a prebiotic it must satisfy three requirements. First, it must not be resistant to the low pH of stomach acid, be broken down by enzymes or absorbed into the GI tract. Second, it must be able to be fermented by the microbes in the microbiome. Third, the growth of gut bacteria can be selectively stimulated by the food and the growth of the bacteria improves your overall health.8

The following foods are considered to be good prebiotics: asparagus, banana, barley, beans, chicory, garlic, honey, Jerusalem artichoke, microalgae, milk, onion, sugar beet, peas, rye, seaweeds, soybean, tomato, and wheat.8