This great guest post was written by Brett Hawes, CNP. I encourage you to go check out his website!
Leaky gut seems to be the latest buzzword in alternative health these days. It has been linked to many health conditions including autoimmune disorders, food allergies, digestive issues, chronic fatigue syndrome, fibromyalgia and rheumatoid arthritis (to name just a few). This has obviously sparked much debate since leaky gut syndrome (LGS) is not an officially recognized medical condition. This has also caused a lot of people to self-diagnose themselves as having LGS (I have seen enough paranoid students pass through my classroom). I can understand why people self-diagnose – symptoms associated with LGS commonly include:
- Chronic intestinal bloating, gas, cramping and pain
- Alternating constipation and diarrhea
- Headaches and roaming muscular pains poor sleeping,
- Lack of concentration, poor mental ability, depression, and anxiety
- Chronic physical fatigue and lethargy
- Complaints of itchy skin, rashes and acne
- Intolerance to many foods or environmental chemicals
Looking at the list above, many people might automatically assume that they have LGS. But, these symptoms are involved with many other health conditions and it would be foolish to embark on a full leaky gut protocol unnecessarily. The first step to take in figuring out whether or not you actually have leaky gut is to get tested. There is a simple urine test known as a lactulose-mannitol test. In short, lactulose and mannitol are sugars that are not normally absorbed. The test requires that you drink this sugar solution and then, a certain amount of time afterward, collect a urine sample. If there is any trace of these sugars in the urine, you have leaky gut. This, unfortunately, is usually where many practitioners stop. We still have not figured out why the gut is leaky or what is driving it. In order to figure this out, let’s back up a step and delve deeper.
What Exactly is Leaky Gut?
LGS describes a pathological increase in permeability of the intestinal lining that causes increased absorption of intestinally-derived toxins, antigens, inflammatory mediators, and, in some cases, intact pathogens. It is a state of physical damage to the integrity of the intestinal lining.
The epithelial cells of the intestinal lining are joined – bridged – by structures called ‘tight junctions’ (TJ). Normally, TJ passageways remain closed. In LGS the TJ fail to remain properly tight. This allows material in the gut to bypass the normal filtering mechanisms, which allows pathogenic bacteria, yeast, and undigested food to exit the gut and gain circulation through the blood. When the immune system reacts to this stream of inappropriate substances, LGS symptoms are expressed.
What is The Driving Force Behind Your Leaky Gut?
This is an extremely important question to ask. There are in fact a couple of different types of LGS, all having slightly more predominant mechanisms as their underlying driving force. I’ll go through these briefly and also share some of the functional medicine lab tests I use in my practice.
Zonulin has received a great deal of attention in the media and has been heralded as a modern medical ‘breakthrough discovery.’ The tight junctions (described earlier) are anchored by zonulin proteins. While the regulation of intestinal permeability remains somewhat mysterious, zonulin is to date the only known physiologic modulator of tight junctions.
Simply put: the more elevated the zonulin levels are, the leakier the gut (Celiacs have been shown to 30 times higher levels of zonulin than non-Celiacs). Gliadin (a component of gluten) affects the intestinal barrier by increasing zonulin. All cereal grains contain many gliadin-like storage proteins and wheat germ agglutinin-like lectins that may aggravate these junctions via this mechanism (which is why it is essential to avoid all grains when treating leaky gut). Excessive exercise and stress can also elevate zonulin. The zonulin-type of LGS has been associated with:
- Auto-immune disorders
- Celiac disease
- Rheumatoid arthritis
- Type 1 diabetes
- Type 2 diabetes in many instances
- Certain cancers, brain cancer, lung cancer
- Multiple sclerosis (MS)
As you can see above, zonulin-mediated LGS is strongly associated with autoimmune disorders. New tests on the market can actually evaluate zonulin biomarkers in the blood. This gives us a much clearer glimpse into how high it really is and provides a benchmark for before and after treatment.
Lipopolysaccharides (LPS) Bacterial Endotoxin
Bacterial lipopolysaccharides (LPS) are the major outer surface membrane components present in almost all gram-negative bacteria and act as extremely strong stimulators of innate or natural immunity. When the immune system scavenges (eats) pathogenic bacteria in the gut, LPS endotoxins are released. While it is common to see elevated levels in the gut itself, LPS should not be in the blood stream. When blood levels of LPS are elevated, it is a clear indicator that you are dealing with some type of bacterial gut infection, dysbiosis or small intestine bacterial overgrowth (SIBO).This is also a clear sign that there is systemic inflammation (LPS cause inflammation) which has very strong correlations with heart disease, cancer, and any systemic inflammatory diseases. LPS has been strongly associated with heart disease in particular.
Diamine Oxidase (DOA) Deficiency
DOA is an enzyme made in our microvilli (gut lining) and is responsible for breaking down histamine in the body. When it is low, the microvilli atrophy (they shrink). This is a completely different form of leaky gut. It is not a Zonulin-mediated leaky gut, where we have tight junctions that are loose. This is the same mechanism whereby NSAID’s cause leaky gut – they erode the microvilli. This causes low enzyme production and can ultimately erode into an ulcer that may perforate the intestinal lining altogether. This type of LGS is often underlying very difficult and complex cases; it makes people very reactive and very non-specifically reactive. Let me explain.
Histamine is a pro-inflammatory compound naturally produced in the body; usually in response to injury. Foods also contain histamine. If we continually injure the gut (food allergies, medications, alcohol, bacteria, yeast, etc) we will consistently produce histamine. Now, if we add histamine containing foods in the diet, that burden increases even more. Throw in a DOA deficiency and you’ve now lost the ability to break down all that histamine. This creates a vicious cycle of perpetual destruction, inflammation and ‘flare-ups.’ As histamine levels fluctuate in the body you will ebb and flow between more and less reactivity when it comes to foods. This type of leaky gut is more strongly associated with lung issues, skin issues, and tachycardia. There is a lot more to the picture when it comes to DOA and histamine, a little too much for a short article like this. I encourage you to research this more as I believe it will come into focus a lot more as time moves on.
Nearly all LGS cases involve food allergies. The most common culprits are grains and dairy but as the gut becomes leakier, you will become allergic to a wider number of foods. It is a wise choice to do a food sensitivity test that includes IgG1, 2, 3, 4 (including complement markers) and IgE. It’s quite a bit to get into here but, in short, this is a far more accurate test in evaluating a wider spectrum of food allergy sub-types. Complements are strong drivers of inflammation but are not tested in regular IgG tests. IgE reactions are immediate reactions and are not checked on any IgG tests. It is vital to identify and remove food allergens. Failure to do so will result in continued to inflammation and damage to the intestinal lining. If this advanced IgG1, 2, 3, 4 (including complement markers) and IgE test is not available to you, you can also do a regular IgG test such as ELISA test. If this is not available (they can cost a fair bit), an elimination diet can be implemented to identify allergens. Experience has shown me that although cost effective, eliminations diets can be quite difficult to comply with.
LGS can be a very complex and lengthy issue to deal with. Having some solid information before embarking on a treatment plan is critical. This gives you and your practitioner a clear target to shoot at and much better understanding of where you are heading. Testing also provides definitive information that keeps both practitioner and patient in check – you can monitor before and after progress, ensuring that the treatment is working and the patient is complying.
In my functional medicine practice, I typically run the following tests (or a combination thereof):
- Advanced Intestinal Barrier Assessment – checks LPS, DOA, zonulin and histamine levels
- Food Allergy Test – IgG1, 2, 3, 4 (including complement markers) and IgE
- Comprehensive Digestive Stool Analysis – a thorough assessment of digestion, absorption, pathogens, inflammation and more
- Leaky Gut Test – lactulose and mannitol
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- Dastych M, Dastych M Jr, Novotna H, Cihalova J. Lactulose/mannitol test and specificity, sensitivity, and area under curve of intestinal permeability parameters in patients with liver cirrhosis and Crohn’s disease. Dig Dis Sci. 2008;53(10):2789-2792.
- 1983 Jun 17;220(4603):1290-2. Localization of wheat germ agglutinin–like lectins in various species of the gramineae. Mishkind ML, Palevitz BA, Raikhel NV, Keegstra K.
- Fasano A. Intestinal Permeability and its Regulation by Zonulin: Diagnostic and Therapeutic Implications. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2012;10(10):1096-1100. doi:10.1016/j.cgh.2012.08.012.
- Identification of human zonulin, a physiological modulator of tight junctions, as prehaptoglobin-2. Tripathi A, Lammers KM, Goldblum S, Shea-Donohue T, Netzel-Arnett S, Buzza MS, Antalis TM, Vogel SN, Zhao A, Yang S, Arrietta MC, Meddings JB, Fasano A. Proc Natl Acad Sci U S A. 2009 Sep 29; 106(39):16799-804.
- Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms.
- Visser J, Rozing J, Sapone A, Lammers K, Fasano A Ann; N Y Acad Sci. 2009 May; 1165():195-205.
- Farhadi A, Banan A, Fields J, Keshavarzian A. Intestinal barrier: an interface between health and disease. J Gastroenterol Hepatol. 2003;18:479–97
- Maes M, Coucke F, Leunis JC. Normalization of the increased translocation of endotoxin from gram negative enterobacteria (leaky gut) is accompanied by a remission of chronic fatigue syndrome. Neuro Endocrinol Lett. 2007;28(6):739-744.
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