The Gut-Brain Axis in Traumatic Brain Injury

It’s no longer a secret that the composition and health of your gut has an substantial impact on the health of the brain and nervous system. Research on the role the gut microbiome has exploded in the last 10 years with blockbuster studies showing that your gut bacteria composition can affect mental health conditions like depression [1] and neurological disorders like Parkinson’s Disease [2].

Although chiropractic is generally associated with bad backs and tight muscles, most chiropractors have a deep seated interest in the connection between the brain, the immune system, and the gut. While there haven’t been any hard studies on the topic, some authors are looking at this connection to see if the gut-brain axis may be a link between head injuries and neurodegenerative disease. This specific topic actually ties into all of my scientific interests in one shot, so you’ll hopefully get a lot from some of the extra content and diagrams I’m going to try to lay out in this article.

A Tale of Two Brains

Most everyone is aware of the importance of the brain in your head, but there is also a staggering number of neurons that exist in your gut. This bundle of nerves in the gut is collectively known as the enteric nervous system (ENS). There are an estimated 500 million neurons in the gut which exceeds the number of neurons in the spinal cord, and makes it the second only to the brain in terms of neural density. This has lead some scientists to affectionately call the ENS the 2nd brain, so maybe making “gut” decisions might not be such a terrible thing (jk).

The number of neurons in the gut might actually be the second most interesting thing about the ENS. The most interesting thing is that the ENS can actually function without talking to the brain if it needs to. The gut has it’s own set of interneurons and integrating centers so that it can carry out reflexes and functions without the help of the brain. In normally functioning humans, the brain does talk to the gut through the vagus nerve, but the vagus nerve can be severed and the gut will continue to work of it’s own power.

The gut is also a MAJOR producer of neurotransmitters for the body which are the chemical currency of the nervous system. The gut produces about 90% of the total serotonin in the body and about 50% of body’s dopamine which can have major implications in the function of the brain and mood [3]. We’ll get into the importance of that a little later.

Shield’s Down: The Gut and the Brain Barrier

The brain and the gut also has some similarities in that both have physiological barriers that have been topics of high interest for neurodegenerative disease.

The gut has a barrier that keeps potentially harmful substances from getting IN to your blood stream while the brain has a barrier to keeps harmful substances in the blood OUT of the brain.

The barrier in your brain is called the blood-brain barrier and it’s fairly well established that disruption of the blood brain barrier is associated with a host of neurological disorders [4]

Intestinal permeability, also known as leaky gut, is also well supported in the literature as a driver of systemic inflammation, but has been subject to a lot of abuse from various practitioners overstating it’s prevalence and significance. While not everything is leaky gut, and not every leaky gut needs an intensive supplement regiment, intestinal permeability is a real phenomenon has the potential to create disease in the gut like Celiac, inflammatory bowel disease, and metabolic syndrome. [5]

Losing these barriers is like losing a layer of defense which can make your body more prone to attack from disease causing agents, or even the cells of your own immune system.

Neuroinflammation — Collateral damage from your Body’s Defenses

So we have these barriers in our gut and our brain that help prevent harmful substances from getting into our blood or into our brains. We know that when these barriers get disrupted that our body is more susceptible to threats from outside the body. However, the increased permeability of these barriers may be the major driving force in threats from the INSIDE of the body.

Our immune system is made up of several classes of white blood cells and proteins that patrol the body looking for any bacteria, viruses, parasites, fungi, or other organisms that may potentially harm us. While the immune system does a remarkable job protecting us, scenarios can arise when the immune system accidentally does the body harm. This is the case in autoimmune disorders like multiple sclerosis, rheumatoid arthritis, Grave’s Disease, and Crohn’s Disease.

The presence of these autoimmune reactions can be the result of an immune system that is isn’t regulated properly or has accidentally built antibodies that can inadvertantly attack the body’s own tissues. When you have a leaky gut, these immune cells can get primed to attack compounds that don’t normally harm the body (think gluten or food allergies). When there is a leaky blood-brain barrier, these immune reactions can occur in the brain and spinal cord which normally tries to keep inflammation OUT. When these reactions occur in or around the brain, it can cause neuroinflammation which can gradually deteriorate brain tissue. Some authors have suggested that post-concussion syndrome may be a form of an inflammatory brain illness, but that hypothesis hasn’t been studied extensively yet. [6]

It is something that’s worth paying attention to because many neurodegenerative disorders seem to have a link to the brain being exposed to chronic neuroinflammation, and surely chronic traumatic encephalopathy would fit that bill.

Microglia: When the Brain’s Helper Cells Go Rogue

Your brain is loaded with non-neuronal helper cells called glia. Glia help support the neurons in your brain by providing protection, insulation, and repair whenever it needs. They take up a huge chunk of brain material and actually outnumber neurons in the brain by a factor of 10.

A special type of glia exists in the brain called microglia. Microglia are macrophages inside of the brain and they help clean up dead or unnecessary debris hanging out in the brain. They play a role in protecting the brain from infections, but they also do really cool things like prune synapses that aren’t used anymore, or get rid or clean up dead brain cells after injury. [Source for graphic and summary]

Like most immune cells, their default setting is turned to the off switch. You don’t want immune cells overly active otherwise they create a lot of inflammation. When infections or injuries arise, these cells become primed and active to help initiate the clean up and repair inside the brain.

This means that they start eating away at dead cells and recruiting other immune cells to create inflammation. Short-term inflammation is essential to healing, so we need these cells to generate inflammation for short periods of time while tissues heal. But sometimes, when a cell gets turned on, the off switch gets broken and it stays on leading to chronic inflammation.

Chronic activation of microglia has been implicated in multiple neurological diseases with autism, MS, and Alzheimer’s Disease chief among them. [7]

The Vagus Nerve — The Bridge for the Gut-Brain Connection

If you’ve been following this blog for a while, you know that I love writing about this cranial nerve because it appears to be relevant in all aspects of our health. You can comb through my previous thoughts on the vagus nerve here.

The vagus nerve is a specialized nerve that comes off the brain stem and is connected to many of the body’s vital organs. It has a particularly important role in the gut-brain axis because it is a primary conduit for the brain in your gut to talk to the brain in your head.

This becomes really important when we consider that the brain acts as a biological thermostat for multiple functions in the body, including regulation of the immune system. It’s been well established that changes in the your gut bacteria can dictate inflammation in the brain [8] and brain damage can influence gut permeability [9]. Many scientists suspect that the vagus nerve is a central player in these phenomenon.

How important is this bridge? Some evidence suggests that the vagus nerve may be a conduit for how rogue proteins in Parkinson’s Disease can spread into the brain.

Concussions: Disrupting the Barriers and Stirring the Pot of Inflammation

So now it’s time to put it all together. How does something like a concussion affect this entire system? Two recent review papers have gone into this concept with some detail, but here are the big ideas [10–11]:

• Traumatic brain injury (TBI) can cause dysautonomia resulting in poor functionality of the vagus nerve and poor motility of the gut.
• Animal models have shown that experimentally induced brain injury can lead to more porous gut permeability within 3 hours of TBI.
• TBI disrupts the blood brain barrier
• TBI will lead to priming of microglia and neuroinflammation. Structural signs of brain injury are correlated to the amount of microglia primed in the brain
• A disrupted gut lining after TBI is more susceptible to rogue bacteria infiltrating the blood stream and creating systemic inflammation. Systemic inflammation can further impact the brain’s microglia promoting more neuroinflammation long after TBI.

In a worst case scenario, the disruption of the gut barrier and the brain barrier allow for a persistent cycle of systemic inflammation and constant activation of brain microglia.

Do we know if this happens in humans yet? Truthfully the answer is no. There haven’t been any experiments done that have looked at this relationship yet so it’s too early to say if this is a real phenomenon that can tie together brain injury and neurodegeneration.

So what probiotic should I take after a concussion?

So the natural question after reading this is what type of treatment do you need after a concussion? When we talk about guts, the usual line of thinking is to think about probiotics, but that probably won’t lead us to the answers people with brain injuries really need.

Remember that big cast of characters we talked about before we addressed the topic of concussion? Here’s a refresher:

• The brain
• The “brain” in your gut (enteric nervous system)
• Intestinal barrier
• Blood-brain barrier
• Microglia
• Vagus nerve

Brain injury is a multi-faceted injury that has wide effects on numerous parts of the body. There’s no magic potion that will specifically hit everything in a positive way. Here are some ways we’ve seen patients improve with problems in the gut-brain axis:

• Cervical, vestibular, ocular rehabilitation with graded exercise is becoming the gold standard in concussion recovery
• Cardiovascular exercise to improve hippocampal and global neuroplasticity
• Correction at the craniocervical junction to improve cerebrospinal fluid dynamics, decrease stress on the blood brain barrier, and improve circulation of neuroinflammatory compounds
• Vagus nerve stimulation to improve neuroplasticity, decrease systemic inflammation, and increase gut repair
• Neurofeedback for plasticity and improve parasympathetic tone
• Pre- and probiotics to repair gut permeability
• Ketogenic/fasting type diets to decrease neuroinflammation and alter gut biome
• Reduction of common dietary gut irritants

There’s a lot more that we could add to this list, but these are some of the most common things that we see that can help some of the more challenging patient presentations.

Will these therapies stop or prevent neurodegenerative diseases? We can’t say for sure, but they are all things that tend to improve the lives of people with early signs of neurological deterioration so time will tell if this can impact the brain injury population as a whole.

1. Marin I, Goertz J, Ren T et al. Microbiota alteration is associated with the development of stress-induced despair behavior. Scientific Reports. 7 Article number: 43859 (2017)
2. Sampson T, Debelius J, Thron T, et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s Disease. Cell. 2016 Volume 167, Issue 6.
3. Stroller-Conrad J. Microbes Help Produce Serotonin in the Gut. Cal Tech Matters Newsletter. April 9, 2015. http://www.caltech.edu/news/microbes-help-produce-serotonin-gut-46495
4. Zlokovic BV. The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron. 2008 Jan 24;57(2):178–201.
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6. Rathbone, AT, Tharmaradinam S, Jiang S, et al. A review of the neuro-and systemic inflammatory responses in post concussion symptoms: Introduction of the ‘post-iflammatory brain syndrome’ PIBS. Brain, Behav. Immun. 46, 1–16 (2015).
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11. Sundman MH, Chen NK, Subbian V, and Chou YH. The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease. Brain Behav Immun. 2017 Nov; 66:31–44.