Written by: Dr. Brandon Brock, MSN, BSN, RN, NP-C, DCN, DCM, DAAIM, BCIM, DACNB, FICC
Structural content edited by: Tara Brock
How Did My Guts, Get to My Head?
SIBO (Small intestinal bacterial overgrowth), that nasty condition where gut flora migrates into the wrong places (large intestines to small intestines) and there is abnormal growth ultimately due to stagnation causing gut distention as a result of methane and hydrogen gas production and eventual breakdown in barriers, infiltration of molecules that can be deemed as antigen and the story just keeps getting worse from there.
Many people sit and suffer in silence with this and they have no diagnosis to speak of because many practicing in the field do not understand this story, or how to fix it, nor know how to test or question the patient about it. The story of pathological intestinal overgrowth can start for a lot of fundamental reasons. Things that protect a person from SIBO include the ability to have adequate gastric secretions, pancreatic enzyme production, gut motility, mucosal immunity, good anatomic valve function in the GI system such as the ileocecal valve that separates the large from the small intestine. I would also include good thyroid function, neurological autonomic output related to the brain, brain-immune interaction, adequate cerebellar function and right brain function as well as left brain function when appropriate and needed. When we look at the basic fundamental understandings of this condition at this point, it is no wonder that those suffering from thyroid disease, autoimmunity, neurodegeneration, head trauma and conditions of the brainstem, cerebellum and cortex can ultimately have a much larger chance of SIBO developing, and if treated and eradicated, never coming back if ALL factors are addressed.
Before I get going down the path of autoimmunity, infection or other metabolic issues it is evident that one thing correlates with all of the aforementioned, and that is appropriate vagal function. That is correct, good brain integration leading to good vagal tone, which generates good stomach acidity, good enzyme formation, gut motility, mucosal blood flow, valve integrity and even immune and liver modulation to an extent. Good brain function and neurochemicals and neurotransmitters also drive the receptors of the hypothalamus (Beta 2 receptors) are imperative to drive the receptors of the hypothalamus (Beta 2 receptors) are imperative to drive Hypothalamic based TRH, which in turn drives the thyroid to generate stomach acidity, protection of the mucosal lining and energy and function to the enteric nervous system for motility that is appropriate to physiological need.
TRH coming out of the hypothalamus goes to the pituitary for TSH (Thyroid Stimulating Hormone) production, but it also goes to the brainstem to activate all preganglionic parasympathetic neurons to give autonomic function that is appropriate in this story, and it is symmetric to the needs and metabolic demands set forth by TSH output from the pituitary to the thyroid to generate T4 and eventual free bioactive T3 that goes to all receptors. It is the meeting point of the endocrine drive for metabolism and the autonomic nervous system is the brains way of contributing autonomically to keep symmetry between the chemical and the neurological.
So to summarize this portion of the story, the brain activates the hypothalamus, which activates the pituitary for TSH (Thyroid Stimulating Hormone) generation, and T4, which then drives gut mucosal integrity. TRH also activates the pontine system to generate appropriate autonomic responses to various stimuli, which will match metabolic demand and blood shunting to various areas. This story is suggestive of physiologic hypothalamic – thyroid – gastric loops and hypothalamic – brainstem –autonomic – gut loops. The two together give a mirrored component of appropriate physiological needs for gut function and the need to be proper and drive the brain to summation and realization for related autonomic needs and fuel delivery to support such thyroid functions.
So, back to the causation of this pathological process being discussed. Many ideas and hypothetical content exists, including some of the aforementioned. One other issue is that the patient can have irritable bowel symptoms, which is common in SIBO. This at times can be as a result of various antibodies and autoimmunity. It is known that ulcerative colitis and Crohn’s, which can be present, as a result of ASCA and ANCA antibodies; however, there are others. AntiGCdtB and antiGvinculin antibodies can also develop from various factors, some including infection as the main drivers. In the end, as bacteria settles, they start to generate gasses that can be measured on the lactulose breath test to be elevated, thus causing possible hydrogen positivity on testing or methane positivity on testing. Hydrogen is notorious for diarrhea and methane constipation. This is important to understand as it pertains to treatment. For instance, if there is mainly hydrogen producers present in the patient and proven on the gas test, Rifaximin might be used with a good yield of outcomes.
Infection as stated can also play a role in this. For instance, C. Jejuni has been shown to generate SIBO through CdtB neurotoxicity. CdtB can then undergo mimicry and cross reactivity can develop, commonly generate antibody production to Vinculin as a result of simple cross reactivity or molecular regulation issues. Vinculin is really part of the mechanism that makes the enteric nervous system summate thus causing the guts to innately move. So post infectious IBS with C.Jejuni, or even E. Coli, salmonella, shigella or camphylobacter can lead to CdtB antibodies which can lead to cross reactivity with Vinculin antibodies and now the bowel becomes irritable and the normal prokinetic movement is significantly stunted or erratic due to changes in the fragile central integrated state of the enteric neuronal structure. This allows the misplaced bacteria to stop and become settled as a result of migration loss and translocate due to gas induced valve opening. Typically these bacteria that translocate are troubling to the host and can support all the pathological processes that occur with SIBO (See diagram at the bottom). One of them is the production of lithocolic acid from these stagnant gatherings, which can produce further enteric neuronal damage and perpetuate the already present Vinculin related slowness. The bacteria hanging out can really eat up large portions of dietary protein, thus causing edema in our peripheral due to albumin loss in the blood, immune deficiency and dysregulation due to immunoglobulin loss from protein globulin depletion, hemoglobin loss and transport proteins that are so vital. These will all ultimately go down to the point of causing many health issues.
This is all due to the loss of protein and the loss of generating albumin and globulin, which allows even more things to happen. Fat (ADEK) and other vital nutrients are now in a process of malabsorption and low levels manifest. This can create so many things, one being a possible co-morbidity of anemia due to iron or B vitamin loss as well as bleeding and reticulocyte elevation thus causing blood loss anemia or even pH buffering issues if hemoglobin is impacted due to globulin changes. This whole process can also cause the tight junctions to break down and allow LPS, which is a toxic byproduct from bacteria, the ability to translocate from gut to blood stream and this ultimately leads to gut inflammation and gut barrier loss. This now allows systemic inflammation to occur which can impact neurotransmitters, further stop thyroid production, conversion problems or many chemicals vital for function, proteomic receptor down-regulation, and finally alter production and down regulation of thyroid receptor sensitivity. It can also cause insulin resistance, chronic pain, weight gain and more inflammation. The multitude of all of the issues listed in that last sentence is beyond the scope of this writing due to sheer space.
So imagine, an infection, this stimulates CdtB antibodies – this cross reacts with Vinculin antibodies – this generates IBS – the gut becomes sluggish and fluctuant – fats are messed up pertaining to absorption – protein is messed up pertaining to absorption – gas is produced – distention occurs – valves open – more bad guys move in – gut mucosal barriers are broken – enteric neurons are further damaged – various things escape from the gut and create systemic inflammation – this alters many neurological patterns and capabilities – the hypothalamus starts to slow – TRH goes down – simultaneously the pituitary stops making TSH for metabolic demands and the brainstem preganglionic neurons slow vagal output – both T4 and vagal function are vital for gut function and as a result, the initial infection has now come full circle with the thyroid and the loss in brain vagal function promoting demise that is much the same as the initial infection.
There is also a loss in immune control and regulation with this mechanism so the overgrowths are not regulated and amplify their own existence, hence the stubbornness and reoccurrence of these overgrowth conditions. To simplify it looks a little like this:
Exposure to an antigen likely occurs3 gut infection ensues – bad guts develop– leaky membranes is inevitable – or dendritic sensitization manifests – immune cross reactivity prevails– damage to the brain and thyroid and possibly other tissues is the end result – and back to guts is eventual. The loops of death, they are all around us, this one happens to go in the following:
- Gut to brain.
- Brain to gut.
- Brain to thyroid.
- Thyroid to brain.
- Brain and thyroid to immune.
- Immune back to the brain and the thyroid.
These patients get sick with NEUROLOGICAL conditions all of the time in addition to the GI symptoms or others. Symptoms are never the exact same from person to person. So the question is this, does infectious disease, gut motility, stomach acid production, autoimmunity in the gut, systemic infection/inflammation and thyroid function have anything to do with brain? The answer is a resounding most likely! Do medications impact this story and thus promote the demise already set in place? They certainly can. If the loops goes around and around enough, you can get total end organ death or failure and then more loops develop and health will spiral out of control.
Over the next several years, Dr. Kharrazhian and I are going to show you functional neurology as it is in a pure science and art; however, there will be the addition of things like the story I just told you, along with medication interactions, nutrition and diet that can be used in conjunction with neurological stimulation in a way that patients can start to control these terrible loops and get rid of the underlying issues and then clinicians can learn to stop the return by making a good GI environment, immune stability, thyroid enhancement, brain activation, mucosal integrity and enteric nervous system activation.
I love these days, when the whole story about the brain and its many underlying agitating factors are coming to light and the field of functional neurology and functional medicine are evolving. It is so amazing that they are evolving together and the more they do, the more it looks like one cannot be totally used without the other. Welcome to the evolution!
Figure One: D.Kharrazian
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