Welcome back to my series on neurodegeneration. So far in this series I have discussed a number of topics including: general concepts about neurodegeneration and genetics in my introductory post, Frontotemporal Lobar Degeneration, Type 2 Diabetes Related Dementia, Alzheimer’s Disease, and considerations for dietary prevention of neurodegeneration related to gluten, sugar, fat, and protein consumption.
- Neurodegeneration: Path to Prevention Part 1 – Introduction
- Frontotemporal Lobar Degeneration: Neurodegeneration The Path to Prevention Part 2
- Type 2 Diabetes Related Dementia: Neurodegeneration the Path to Prevention Part 3
- Alzheimer’s Disease: Neurodegeneration the Path to Prevention – Part 4
- Preventing Neurodegeneration with Diet Part 1 – Gluten and Sugar
- Preventing neurodegeneration with Diet Part 2 – Fat and Protein
Today I will be moving away from how a proper dietary macronutrient profile can possibly reduce the risk of neurodegeneration to some cutting edge discoveries surrounding the gut microbiome in relation to what is called the gut-brain axis and it’s possible impact on brain functioning. Before I begin however, I feel it important to mention that the vast majority of the evidence discussed (specific to gut-brain axis) comes from animal studies and hypothesised mechanisms of action. Notwithstanding the above, it is still becoming quite clear that the well accepted 2 way gut-brain axis communication could now possibly be called the microbiome-gut-brain axis due to the recently discovered impact our gut bacteria have on this 2 way communication process (1). Below I will be discussing the relation between our gut-microbiome with systemic and CNS inflammation, genetic expression (epigenetics), and direct influence on neurodegenerative pathology.
Gut-Microbiome and Inflammation
If you recall from my previous posts in this series, I provided clear evidence that inflammation within the central nervous system is central to neurodegeneration. I also provided evidence showing that, for a number of neurodegenerative conditions, elevated systemic (outside of the central nervous system) inflammation is also present. Moreover, I provided evidence that inflammatory mediators present in the periphery (outside the central nervous system) can pass through and/or negatively influence inflammatory mediators in the central nervous system. All of the above leading to the conclusion that it is likely in our best interest to limit as many causes of low grade chronic inflammation as much as possible, particularly if you are at genetic risk of neurodegeneration.
What is becoming more evident in the scientific and practitioner world these days is that the composition and activity of our gut microbiome can directly influence our immune system and the regulation of inflammation in our bodies (2, 3, 4, 5). There are many mechanisms leading to this relationship (leaky gut, pro-inflammatory mediator production, etc) and I will not bore you all with the specifics, but what is important to know is that proper gut bacteria composition regulates the immune system while inappropriate gut bacteria composition dysregulates the immune system, causing issues such as chronic systemic inflammation. Unfortunately, we are not yet fully sure what comprises a completely healthy microbiome population as this can differ significantly from person to person; however, there are projects currently under way to try and nail down the type, number and activity of a healthy human gut microbiome.
Microbiome-Gut-Brain Axis and Neurodegeneration
Now on to the cool stuff, at least I find it cool. As I mentioned above, recent evidence is pointing to a direct link between our microbiome and our central nervous system (1, 6, 7, 8, 9, 10, 11). While it is fairly accepted knowledge that there is a direct gut-brain connection, termed the gut-brain axis, the above noted recent evidence is strong enough to indicate that our gut microbiome probably plays a primary role in this communication axis, leading to the suggested new term microbiome-gut-brain axis.
So, obviously if our gut can communicate directly with our brain, it is likely that brain and psychological health may be impacted by this relationship. But how, and how might this relate to neurodegeneration?
First lets discuss the minimal evidence for humans. One study (7, 9) showed that, women with no gastrointestinal issues, who were fed a fermented milk product for a 4 week period had positive alterations in brain activity during a mental function test. Another study (10) theorized that the epidemiological evidence showing that smokers and coffee drinkers have a lower risk of Parkinson’s Disease (please don’t smoke) could be do to the fact that these 2 substances can affect our gut bacteria in a way that mitigates intestinal inflammation, leading to less pathological (misfolded) proteins in the enteric nervous system (see definition below), and thus reducing the risk of Parkinson’s disease. A further study (11) discussed the gut-brain access and it’s relationship to Schizophrenia. Specifically, they proposed mechanisms of how disrupted gut bacteria could impact this disease through increased inflammatory mediators and decreases in Brain-Derived Neurotrophic Factor (BDNF), which is vitally important for brain development, neurogenesis and brain plasticity.
When we look at animal studies, there is a bit more evidence of the above, along with more suggested mechanisms of how this communication actually takes place. While you may not know this, our gastrointestinal tract nervous system (enteric) is actually connected right to our brains via the vagus nerve. However, our enteric nervous system can actually functional all on it’s own even when the vagus nerve connection is severed, leading to another term for the enteric nervous system…Second Brain. So, now that we know our GI tracts are connected directly to our brain, what mechanisms have been suggested linking our gut bacteria to behaviour and conditions involving the central nervous system? It is suggested that our microbiome communicates with our brain via the autonomic nervous system, the enteric nervous system, the neuroendocrine system, the circulatory system, the lymphatic system, and the immune system (6, 8). To illustrate the possibilities here, I want to note that some bacteria can produce signalling molecules that can be transported through the intestinal barrier and shuttled by our circulatory and lymphatic systems to target organs (i.e The Brain) (8). Pretty amazing stuff!
In the first post in this series I discussed information on epigenetics, the fact that our actual DNA is not sufficient to express all human individual traits. Specifically, a genetic mutation is not always sufficient to cause the specific disease it is linked to; the activation and/or deactivation of that gene, or other genes that increase or decrease the risk of the condition, is what may be more important. The environmental factors that play with gene activation are epigenetic factors. Interestingly, it has been suggested that the gut microbiome could actually be a significant epigenetic entity (1). Many molecules and metabolic byproducts associated with certain gut bacteria have been shown to directly affect DNA transcription and related processes (i.e. gene activation) (1). For instance, gut bacteria, via their metabolism, are one of the main producers of short chain fatty acids, which have been linked to genetic processes involved in neuroprotection and neuroregeneration (1)! Basically if we want our genes to be utilized properly we must keep our epigenetic entity properly regulated.
Finally, for an example of a direct link to neurodegeneration, BMAA, a neurotoxin found to be elevated in ALS and Parkinson’s patient brains, has been hypothesized to be created by an intestinal bacteria, and stress, GI disease and malnutrition negatively impact the production of BMAA (6). BMAA has even been shown to be part of the misfolded proteins found in nervous system tissue of individuals with Alzheimer’s, Parkinson’s, and Prion Diseases (6).
Notwithstanding the above, there is not a ton of information linking neurodegenerative diseases directly to the microbiome-gut-brain axis, but as I have outlined in my previous posts in this series, we know that inflammation is a key player, along with the obvious neuronal cell death. So, we definitely want to protect the brain by reducing risks for inflammation and optimizing our ability for neurogenesis and brain plasticity. It is simply becoming more clear that our gut microbiome plays a key role in these factors so we should try and keep it healthy.
The important takeaway here is that we should be doing our best to ensure our guts are full of healthy helpful bacteria and the best way to do this is to eat a whole food (no processed food), low sugar, low Omega 6/rancid oil diet full of pro and prebiotic foods. So, don’t hesitate to eat fermented vegetables (sauerkraut, kimchi), kombucha, kefir water, and fermented milk products (yogurt, kefir, aged cheese) if you tolerate dairy. It may also be beneficial to connect with a practitioner who can recommend a high quality probiotic supplement.
I hope this post has been informative. I know it was for me when I was researching it!
The Barefoot Golfer