These are notes from an interview with Dr Datis Kharrazian about the gut/brain axis:
As a doctor, it really bothers him when he doesn't have answers for patients. This motivates him to do more research. He is the author of
Why Do I Still Have Thyroid Symptoms? When My Lab Tests Are Normal. He has also written a more recent book about the brain called
Why Isn't My Brain Working? This is an interview in which he talks about the bigger picture behind these questions, the gut brain axis.
The existence of a gut/brain axis is well established in medical research and literature, there are even medical journals devoted to this topic. He says the issues around the gut/brain axis are bigger than just yeast overgrowth, and infections, and food reactions..they can involve the neurology of the gut and got/brain axis itself. Many neurodegenerative diseases begin in the gut. One of the first considerations is if the person has motility issues, because that can indicate that the brain is involved. Gut motility is how we move food through our bodies from eating it to elimination. This includes constipation, in which someone may need to drink coffee or use laxatives in order to have a bowel movement. Motility problems do not always indicate gut/brain axis involvement, he says, but do indicate that this needs to be considered and ruled out (this is called "neurogenic" when the problem has to do with poor control from the brain).
Poor gut motility means food is not moving through the gut well enough, which leads to fermentation, yeast and bacterial overgrowth, enzyme deficiencies (the brain is needed to properly release digestive enzymes), an environment favorable to parasites, and inadequate hydrochloric acid release. The first step in ruling this out is to look at medical history...is there evidence of constipation, slowed passage of food? The next step is to listen for bowel sounds which also give a clue about how well the system is moving. Poor motility will result in fewer bowel sounds, as the muscles aren't moving as much. Looking at vagal nerve function is also useful, and can be checked by seeing how much the arches on the palate move when the patient says "ah", as these arches are enervated by the vagus nerve. He also says that as neurons are beginning to degenerate, they sometimes begin to fire on their own, so you can see spasms- in this case, spasms in the arches as the person says "ah". This can also manifest as an overactive gag reflex or no gag reflex.
The vagus nerve is in the brainstem. (
This may be a connection with EDS, which can cause compression of the brainstem, and is often associated with poor gut motility and serious gut problems). He says that if a person has gut dysfunction stemming from the gut/brain axis, that taking digestive supports such as enzymes and supplements, and following a clean diet, may be important to keep the gut functioning to some extent, but won't fix the problem. Fixing the problem means addressing it from the brain down. The brain needs to activate the vagus nerve, which then needs to activate the gut. One exercise to build this plasticity back into the brain is to gargle vigorously several times per day. The vagus nerve is next to a part of the brain that is involved in producing tears, and people may need to gargle with an intensity enough to produce tears. Another way to activate the gut/brain axis and build strength is to induce a gag reflex, which can be done with a tongue depressor. The third thing is to have patients do a coffee enema once a day, not for detox reasons, but to induce the urge to have a bowel movement, so that the person can then "practice" inhibiting the urge as long as possible, which also builds strength into the gut/brain axis. It is important to maintain gut function with supports such as clean diet, enzymes, etc, in order to minimize inflammation, because inflammation in the gut can also lead to problems in the gut/brain axis (it goes both ways). Singing loudly can also stimulate the vagal muscles in the back of the throat.
The frontal cortex fires into the vagal brainstem motor nuclei, that fires into your enteric motor system. There are also fibers from the insular cortex that fire into somatotopic areas and autonomic areas that control blood flow and digestive enzyme secretion. The insular cortex and the hypothalamus fire into a part of the brainstem called the nuclear ambiguous, which controls autonomic function in the gut. Parasympathetic stimulation of the gut causes blood flow, enzyme secretion, motility, and generally good function of the gut.
SIBO (Small Intestine Bacterial Overgrowth) is when bacteria from the colon migrate up into teh small intestine, and once there they are reactive to many food components and this leads to bloating, pain, and poor gut function. SIBO begins with a dysfunction in the migrating motor complexes, and failed valve control, which is neurogenic based. It is about the brain or gut nervous system failing. SIBO generally indicates a degenerative gut neural problem, and many people with it have early signs of Parkinson's, have had traumatic brain injury, etc. Standard treatment uses prokinetic drugs (to stimulate movement in the gut), and antibiotics, lead to almost a 100% rate of relapse. Those methods don't actually address the underlying cause. Also, early intervention is extremely important. Neural plasticity works both ways, so as function is lost, it becomes harder and harder to get back, and he says that there is a point of no return.
Ultimately, he says, gut/brain axis problems begin in the brain. One example is Parkinson's Disease. He says that Parkinson's is an alpha synucleinopathy, in which a protein called alpha synuclein builds up between nerves, interferes with their ability to communicate, and leads to them degenerating. This degeneration begins in two places...it starts in the gut, leading to gut dysfunction, and then goes into the olfactory bulb, causing the sense of smell to diminish and eventually be lost. Stiffness is another of the early signs. Another example of brain involvement is with dementia, which leads to less output from the pons. Top supplements to support the brain include things that improve acetylcholine function, since the vagus nerve and the gut enteric system are predominantly acetylcholine driven. Examples include Huperzine and Galantamine which can be purchased OTC. Galantamine is the most used medication for dementia in the world, but not in the US.
There is a strong relationship between brain function and leaky gut, which is more correctly called "intestinal permeability". In animal studies, intestinal permeability can be observed within 3 hours of a brain injury. In one study, animals that experienced traumatic brain injury but also had electrical stimulation of the vagus nerve, did NOT develop intestinal permeability. There are also studies in humans showing that traumatic brain injury results in clear gut dysfunction and vagus nerve problems. The autonomic system carries blood to the gut, blood is what carries everything to the gut that it needs to function and stay healthy. He also says this is why we see so much gut dysfunction in autism, and he points out that this requires treatment of the gut/brain axis, in addition to gut support. Inflammation in the gut travels back to the brain, via the gut-to-brain axis, and triggers glial activation and an inflammatory cascade in the brain.
Celiac research is finding that a chemical called zonulin is released with gut permeability, which also opens up the tight junctions in the brain, leading to permeability of the blood-brain-barrier. Zonulin was first discovered by researchers studying the effects of cholera, and found to be a protein that causes the tight connections between intestinal cells, called tight junctions, to open up. There are now studies coming out showing that people who have inflammatory bowel disease also have white matter lesions in the brain, which means that the gut inflammation is starting to cause brain degeneration- it's causing the myelin (the protective covering of nerves) to be destroyed.
His preferred way to test for intestinal permeability is through Cyrex labs, using array number 2. This test looks for both trans-cellular and paracellular permeability in the gut, based on which antibodies are elevated. This gives a good sense of whether the blood-brain-barrier is also leaky. Leaky gut used to be tested for with a test called the Lactulose/mannitol test, in which two sugars were given, and then tested for in the urine. Lactulose is such a large sugar that it should not make it into the blood from the gut, so if it appears in large amounts in the urine, it is clearly gettingthrough somehow. Another quick method is to take GABA, a calming neurotransmitter, which does not normally cross the blood-brain-barrier. If a person feels different after taking it they know their BBB is compromised (most people will feel calm, but some have a paradoxical effect and will feel hyper). Now, Cyrex labs also has a panel that looks for antibodies against the BBB.
The immune system in the brain is different than it is in the rest of the body. In the brain, the immune cells are called glial cells, and once turned on, they do not turn off, the way that immune cells in the rest of the body can be shut off. They eventually die, but they will recruit new cells to take over before they die. There are studies showing that turmeric and luteolin can actually shut off the glial activation. When people have brain inflammation, the speed between neurons slows down, which people experience as brain fog, memory problems, sluggish thinking, etc.
People who experience traumatic Brain Injury frequently develop autoimmunity. The gut and the brain communicate both ways, back and forth with each other. Many peptides in the gut, such as CCK and some enzymes, are known to be neurologically active in the brain. There is now a lot of evidence in the scientific literature that once intestinal permeability occurs, autoimmunity frequently follows. You don't need the brain to be involved at first, the standard american diet is pro-inflammatory and can cause gut permeability directly, which then causes glial activation in the brain. Once the gut is compromised, people tent to react to GMOs, soy, and hybridized foods such as modern wheat. He says the reason that people tend to feel better on a paleo-type is because these newer proteins tend to be the most immune reactive.
Autoimmunity is a condition in which the immune system begins to attack itself, it is referred to as loss of self-tolerance. Chronic inflammation disrupts Treg cells, which are critical to maintaining self-tolerance. As we get more intestinal permeability, we get more inflammation, and our immune systems become more over-zealous, which then leads to loss of chemical tolerance (to chemicals in the environment such as gasoline fumes or perfume), which cause triggering events, which then makes the immune system go crazy making auto antibodies for various tissues in the body. He uses a panel from Cyrex to look for antibodies against a wide variety of targets. It turns out that finding antibodies is predictive of future illness.
Gluten is very inflammatory, and cross reacts with the brain. Gluten antibodies can target parts of the brain through a process of molecular mimicry. Antibodies against gluten have been shown to cross react with cerebellar Purkinje cells as well as to
synapsin (a protein found in all neurons), among other things. Gluten is not the only concern with wheat, WGA (wheat germ agglutinin) causes similar issues, and is highest in sprouted wheat. When testing for celiac, they have found that antibodies for transglutaminase 2 target the gut, for transglutaminase 3 target the skin, and transglutaminase 6 targets the brain. In testing of people with gluten antibodies, about 20% have transglutaminase 2 while more like 60% have transglutaminase 6. About 60% of gluten-reactive people do not have gut symptoms but do have brain symptoms. He says that it just happened that gastroenterologists "found" gluten first, so gluten-mediated autoimmunity became though of as a gut disease.
As for his diet recommendations, he says in a simple sense it's the paleo diet. However, what they have found is that even paleo allowed foods can cross react in many autoimmune diseases. So in the future, he feels that people will be tested for which antibodies they produce, and then will have a customized diet that avoids the foods that lead to reactions in their own bodies, so it will be more specific than "just" the paleo diet.
