Dr.Brock Lectures

Dr. Brock Talks

Dr. Brock

by

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:

  1. Gut to brain.
  2. Brain to gut.
  3. Brain to thyroid.
  4. Thyroid to brain.
  5. Brain and thyroid to immune.
  6. 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

References

  1. Petitpierre M, Gomowski P, Girard JGP. Irritable bowel syndrome and hypersensitivity to food. Ann Allergy.1985;54:538-540.
  2. Maxton DG, Martin DF, Whorwell PJ, Godfrey M. Abdominal distension in female patients with irritable bowel syndrome: exploration of possible mechanisms.  Gut.1991;32:662-664.
  3. Lea R, Houghton LA, Reilly B, Whorwell PJ. Abdominal distension in irritable bowel syndrome (IBS): is there a relationship to visceral sensitivity?  Gastroenterology.2003;124:A-398.
  4. Lasser RB, Bond JH, Levitt MD. The role of intestinal gas in functional abdominal pain.  N Engl J Med.1975;293:524-525.
  5. Silverman DHS, Munakata JA, Ennes H, Mandelkern MA, Hoh CK, Mayer EA. Regional cerebral activity in normal and pathologic perception of visceral pain.  Gastroenterology.1997;112:64-72.   
  6. Chadwick V, Chen W, Shu D.  et al.  Activation of the mucosal immune system in irritable bowel syndrome.  Gastroenterology.2002;122:1778-1783.
  7. Pimentel M, Chow E, Lin HC. Eradication of small intestinal bacterial overgrowth reduces symptoms in irritable bowel syndrome.  Am J Gastroenterol.2000;95:3503-3506.
  8. Pimentel M, Mayer AG, Park S, Chow EJ, Hasan A, Kong Y. Methane production during lactulose breath test is associated with gastrointestinal disease presentation.  Dig Dis Sci.2003;48:86-92.
  9. Pimentel M, Kong Y, Park S. IBS subjects with methane on lactulose breath test have lower postprandial serotonin levels than subjects with hydrogen.  Dig Dis Sci.2004;49:84-87.
  10. Vantrappen G, Janssens J, Hellemans J, Ghoos Y. The interdigestive motor complex of normal subjects and patients with bacterial overgrowth of the small intestine. J Clin Invest.1977;59:1158-1166.
  11. Van Felius ID, Akkermans LM, Bosscha K.  et al.  Interdigestive small bowel motility and duodenal bacterial overgrowth in experimental acute pancreatitis.  Neurogastronterol Motil.2003;15:267-276. 
  12. Berg RD, Wommack E, Deitch EA. Immunosuppression and intestinal bacterial overgrowth synergistically promote bacterial translocation. Arch Surg.1988;123:1359-1364.
  13. Gwee KA, Collins SM, Read NW.  et al.  Increased rectal mucosal expression of interleukin 1beta in recently acquired post-infectious irritable bowel syndrome. Gut.2003;52:523-526.
  14. Tornblom H, Lindberg G, Nyberg B, Veress B. Full-thickness biopsy of the jejunum reveals inflammation and enteric neuropathy in irritable bowel syndrome.  Gastroenterology.2002;123:1972-1979.
  15. Collins SM. A case for immunological basis for irritable bowel syndrome.  Gastroenterology.2002;122:2078-2080.
  16. Deitch EA, Specian RD, Berg RD. Endotoxin-induced bacterial translocation and mucosal permeability: role of xanthine oxidase, complement activation and macrophage products.  Crit Care Med.1991;19:785-791.
  17. Goyal RK, Hirano I. The enteric nervous system.  N Engl J Med.1996;334:1106-1115.
  18. Veale D, Kavanagh G, Fielding JF, Fitzgerald O. Primary fibromyalgia and the irritable bowel syndrome: different expressions of a common pathogenetic process. BR J Rheumatol.1991;30:220-222.
  19. Hasko G. Receptor-mediated interaction between the sympathetic nervous system and immune system in inflammation.  Neurochem Res.2001;26:1039-1044.
  20. Besedovsky H, del Rey A, Sorkin E, Da Prada M, Burri R, Honegger C. The immune response evokes changes in brain noradrenergic neurons. Science.1983;221:564-566.
  21. Rivier C. Effect of peripheral and central cytokines on the hypothalamic-pituitary-adrenal axis in the rat. Ann N Y Acad Sci.1993;697:97-105.
  22. Anisman H, Merali Z. Cytokines, stress and depressive illness: brain-immune interactions. Ann Med.2003;35:2-11.