Susan was experiencing severe bloating, gas and diarrhea. She had been to see her GP, 3 Gastroenterologists. All her tests were normal including bloodwork, an endoscopy and a colonoscopy. No one could explain her symptoms. Like most people in her position, Susan began to look for answers on the internet. Eventually, she came across an article on a condition known as leaky gut. Her symptoms appeared to match those of leaky gut. Her question was what were best leaky gut tests.
In this article, we will cover the fundamentals basics of leaky gut, is testing for leaky gut a good idea, and the two best leaky gut tests.
The Fundamentals of Leaky Gut
A leaky gut is a popular term that describes a condition where the lining of the intestines is not functioning correctly. The correct medical term for leaky gut is increased intestinal permeability.
The intestinal lining covers a surface area of about 400 metres squared and requires about 40 per cent of the body’s energy expenditure. That is pretty extraordinary when you think that the brain needs only 20 per cent of the body’s energy expenditure.
This fact tells us that the intestinal lining is essential to our health.
The gut is a hollow tube that connects the mouth to the anus. So, everything that is inside of the gut is technically outside of the body. Therefore everything that is inside of the gut is not technically inside of the body.
Therefore anything that is in the gut to move into the body has to cross that intestinal lining. A fundamental function of the intestinal lining is to let in things that should get in and keep out things that should not stay out.
When certain conditions are present, the intestinal lining’s capability of doing that task breaks down, and then all kinds of problems can happen.
Many factors can interfere with the function of the intestinal lining including:
- A western-type inflammatory diet, lacking in fermentable carbohydrates and fermented foods
- Bacterial, viral, parasitic infections
- Fungal overgrowth
- Heavy metals
- Certain medications like proton pump inhibitors, antibiotics, or NSAIDs
- Lifestyle factors like chronic stress or sleep deprivation or inappropriate physical activity, like too little or too much
- Inadequate immune stimulation during our developmental period. Insufficient immune stimulation is known as the hygiene hypothesis. Better hygiene has done a lot to reduce acute infections, but these overly sterilised environments may have contributed to immune dysregulation because our immune systems aren’t adequately stimulated.
There are other factors which we call endogenous factors. Endogenous means they are factors that occur inside of the body that can contribute to leaky gut.
Endogenous factors include chronic inflammation, SIBO, or gut-brain axis problems
Is testing for leaky gut a good idea?
In my opinion, a leaky gut is almost always a symptom of a deep-seated underlying issue, meaning that the underlying problem comes before a leaky gut.
Causes of a leaky gut may include any of above factors that interfere with the function of the intestinal lining.
One of the critical principles of functional medicine is that we want to get to the bottom of what is causing symptoms or even manifestations of a disease. We want to remove or address those causes or triggers before we try to do anything about the symptom or the sign. The more we can get to the root of the problem, the more effective the intervention will be.
In other words, by suppressing symptoms, it is going to be less effective, and will not last for as long because we have not addressed the underlying cause.
So with intestinal permeability, if we remove the triggers that are causing leaky gut in many cases, you will not need to address intestinal permeability because it will take care of itself.
One of the astonishing things about the cells in the gut is they regenerate every two to three days. Therefore if you remove the triggers that are causing the problem, the cells will revive and the tight junctions can restore themselves, and the intestinal permeability will disappear.
Hence typically in my practice clinic, before looking at a leaky gut, I will test and treat the triggers such as food sensitivities, gut infections and stress. If the patient is still having problems that we could associate with leaky gut, at that point, I will consider testing for intestinal permeability.
Testing options for intestinal permeability
If you look at the research, many different leaky gut tests have been used to define or identify intestinal permeability. Some of these are more common than others, but I am just going to mention a few different ones, and then I will tell you what I use in my practice and what I recommend.
The first is the lactulose/mannitol permeability assay. This test uses molecules, sugars, long-chain sugars called oligosaccharides, and I will explain a little bit more about that in a later.
The second test is an antigenic permeability screen. This test looks at antibodies to particular antigens like lipopolysaccharides and then also antibodies to endogenous molecules like actomyosin, occludin and zonulin. These are proteins that the body produces in the gut that help to regulate tight junction permeability, the structure of the gut and determine whether the gut is permeable or not.
The next marker that researchers sometimes use in studies is an organic acid called D-lactate or D-lactic acid. D-lactate is different from lactic acid that you may have heard about that can be high after exercise. This organic acid is a product of bacterial metabolism which is produced in the gut. Some studies have shown a correlation between high D-lactate and increased intestinal permeability.
Butyrate, which is a short-chain fatty acid, has been investigated as a potential marker for intestinal permeability. Low butyrate is a sign of leaky gut.
Finally, zonulin is a protein that regulates the tight junctions in the gut has been investigated as a marker for intestinal permeability.
What Are The Best Leaky Gut Tests?
In terms of clinical practice and what is readily available and has been most validated by the scientific research, the lactulose/mannitol test and the antigenic permeability screen are the two best leaky gut tests.
The Lactulose/Mannitol Test
The lactulose/mannitol test involves measuring levels of two sugars in the urine after the patient consumes those sugars. By looking at the ratio of the two sugars in the urine you can tell you whether the gut is permeable.
The lactulose/mannitol test is available through Genova Diagnostics.
There are some shortcomings of lactulose/mannitol testing.
One of the issues is that the transport of lactulose or mannitol through the gut barrier is not actually or not necessarily an indicator of a malfunction of the intestinal tight junctions. In other words, a positive result doesn’t necessarily mean that there is intestinal permeability present.
There are a lot of variables that can influence the uptake of the sugars, like GI motility, use of medication like NSAIDs, the surface area of the intestine, gastric emptying, and mucosal blood flow so these variations can affect the result.
Another issue is that some studies have shown that only large molecules (over 5,000 daltons) can change the permeability of intestinal epithelial cells and then result in an inflammatory response in the body.
Lactulose and mannitol are below 500 daltons, which suggests that they may not be appropriate as challenge molecules for an intestinal permeability test.
There are ways to increase lactulose/mannitol testing accuracy including:
- Avoiding foods containing lactulose 24 hours before the test. Lactulose is found in heat-processed dairy and non-dairy beverages such as soy milk and some yoghurts.
- Avoid mannitol for 24 hours before the test. Mannitol is found in brown seaweed, celery, carrot, coconut, cauliflower, cabbage, pineapple, lettuce, watermelon, pumpkin, squash, cassava, pea, asparagus, coffee, olives and berries, and chewing gum.
- Avoid dairy products for 24 hours before the test.
- On the day of the test avoid drinking too much water.
The Antigenic Permeability Screen
The second test for leaky gut is called the antigenic permeability screen. This test was developed by Doctor Aristo Vojdani at Cyrex Labs.
In large part, Dr Vojdani developed the test because of the shortcomings of the lactulose/mannitol test.
Doctor Vojdani wanted to create a test that would better reflect pathological permeability of the gut. So instead of using larger sugars, he decided to screen for antibodies to proteins and bacterial endotoxins, since those are the primary concern when it comes to immunoreactivity.
We know that the uptake of antigens, proteins and bacterial endotoxins, plays a significant role in the pathogenesis of a gastrointestinal and autoimmune disease.
Many studies are showing that the inappropriate transfer of proteins and endotoxins from the gut into the bloodstream initiates an inflammatory response and can contribute to autoimmune disease. This understanding explains the connection between leaky gut and autoimmune disease. Less than 10 per cent of subjects with a genetic susceptibility to autoimmune disease progress to having a clinical autoimmune disease in their lifetime. This fact suggests that environmental triggers like toxic chemicals and infections and dietary proteins are probably involved in the development of autoimmune disease.
The Antigenic Permeability Screen is a blood test. This test is only offered by one lab, Cyrex Labs, and is called Cyrex Array 2.
This test needs to be ordered by a healthcare practitioner who is registered with the Cyrex.
The test involves drawing a blood sample and then testing for antibodies to lipopolysaccharide, IgM, IgG and IgA antibodies,
In practice, for the reasons I explained above I do not check for intestinal permeability very often. Typically I tend to look at the underlying cause of intestinal permeability and address that first. So although the mannitol/lactulose and antigenic permeability screen are the best leaky gut tests, If I do a sound job with addressing the root, in most cases, the intestinal permeability will resolve on its own.
When I do test for permeability, I use the Cyrex test.
This article is not intended to provide medical advice, diagnosis or treatment.
Now I’d like to hear from you. Let us know in the comments below.