Many people reading this are familiar with leaky gut syndrome. This condition involves damage to the enterocytes (cells of the small intestine). What happens is that one or more factors will either cause damage to the tight junctions connecting the enterocytes, and/or will actually penetrate these cells. This results in an increase in intestinal permeability (a leaky gut), which allows proteins and other larger molecules to pass into the blood stream, and in turn can trigger an autoimmune response. This is a mechanism of autoimmunity, and some claim that all autoimmune conditions involve an increase in intestinal permeability. In other words, some suggest that you can’t have an autoimmune condition such as Graves’ Disease or Hashimoto’s Thyroiditis without having a leaky gut. But is this really true?
Dr. Alessio Fasano has done a lot of research on intestinal permeability and autoimmunity. In a journal article entitled “Tight Junctions, Intestinal Permeability, and Autoimmunity Celiac Disease and Type 1 Diabetes Paradigms”, Dr. Fasano concluded that “Genetic predisposition, miscommunication between innate and adaptive immunity, exposure to environmental triggers, and loss of intestinal barrier function secondary to dysfunction of intercellular tight junctions all seem to be key components in the pathogenesis of autoimmune diseases.” (1) [1] This journal article was written in 2009, and while his theory that a loss of intestinal barrier function is a key component in the development of an autoimmune condition still hasn’t been proven, it hasn’t been ruled out either.
Different Methods Of Determining A Loss of Intestinal Barrier Function
There are numerous tests available which can help determine whether someone has a loss of intestinal barrier function, which is synonymous with an increase in intestinal permeability (leaky gut). The classic method of determining whether someone has an increase in intestinal permeability is through the lactulose/mannitol test, which is a urine test. Lactulose is a larger molecule, and if someone has a healthy gut this molecule shouldn’t be absorbed. Therefore, if someone does this test and there are large amounts of lactulose in the urine then this should confirm that the person has a leaky gut. But how accurate is this test? Well, a study in 2008 concluded that the lactulose/mannitol ratio had the highest diagnostic value to assess intestinal permeability (2) [2]. Of course one has to keep in mind that this was before other newer testing methods were developed, such as the intestinal antigenic permeability screen from Cyrex Labs. Another study looked to determine the value of the lactulose/mannitol test in detecting intestinal permeability in those people with Celiac disease (3) [3]. The study showed that the sensitivity of the test was 87% in the screening situation and 81% in the clinical situation.
A few newer tests have been developed in recent years. The company Cyrex Labs has developed a test called the intestinal antigenic permeability screen (the Array #2), which is a blood test that measures the immune system response to an increase in intestinal permeability. It specifically tests for the presence of antibodies against actomyosin, occludin/zonulin, and lipopolysaccharides. Since this test is relatively new I couldn’t find any studies showing the sensitivity of it, although I can say that I have used the test on many of my patients over the last few years and find it to be a valuable test. And many other healthcare professionals use Cyrex Labs as well. The company Dunwoody Labs also has a test for intestinal barrier function, as it tests for zonulin, which is a modulator of intercellular tight junctions. High zonulin levels are found with an increase in intestinal permeability. Once again, I’m not aware of any studies which show how sensitive this test is.
Positive Autoantibodies And A Negative Leaky Gut Test?
Most people reading this know that my practice focuses on thyroid and autoimmune thyroid conditions. And so I see a lot of people with Graves’ Disease and Hashimoto’s Thyroiditis. Although I don’t test everyone for the presence of a leaky gut, over the last few years I have run a decent number of these tests. While some of my patients have obtained the lactulose/mannitol test, most of the time I have recommended the Array #2 from Cyrex Labs. And while a lot of these tests have come back positive, I also have had some come back negative while at the same time the person tested positive for thyroid antibodies.
So what exactly does this mean? Well, this either means that Dr. Fasano’s theory is incorrect, or it means that there are flaws with the intestinal permeability tests. Although the lactulose/mannitol test has a high sensitivity, it still is possible that it can fail to detect an increase in intestinal permeability in some cases. And I suppose the same can be true with the Cyrex Labs testing. With the Array #2, if someone has suppressed immunoglobulins then this can cause a false negative result, and so if someone has very low levels I will usually have them do serum testing for immunoglobulins A, G, and M, as these are the ones utilized on the panel. And while I’ve had a few patients with suppressed immunoglobulins, in most of the cases where someone had a negative intestinal permeability test, their immunoglobulins were well within the reference range.
Is It A Waste Of Money To Test For A Leaky Gut?
Based on what I just stated you might wonder if it is worth testing for a leaky gut. Some healthcare professionals do bypass the testing and assume that everyone with an autoimmune condition has a leaky gut. I’m not suggesting this approach is wrong, as there are times when I will do this as well. In other words, if I strongly suspect that someone has a leaky gut then I very well might put the person on a gut repair protocol without having them spend the money on additional testing. On the other hand, many times I will give the patient the option of choosing to do additional testing, or to bypass the testing and follow a gut repair protocol.
Although testing for a leaky gut does have some flaws, one also has to consider the benefits. For example, if someone gets a test for a leaky gut and it comes out positive, this not only might be revealing the cause of autoimmunity, but it also provides a baseline reading. In other words, if someone tests positive for a leaky gut and is put on a gut repair protocol, one can choose to do a follow-up test at a later date as a way of monitoring the patient’s progress. Or, perhaps one won’t do another test if the person seems to be progressing in all other areas, but will only do a retest if the person isn’t recovering as expected. Obviously different natural healthcare professionals will have different approaches, but while I don’t think everyone needs to be tested for a leaky gut, I do think that such testing has some value.
What Should You Do If The Leaky Gut Test Is Negative?
Another important question to ask is the following: if someone has elevated thyroid antibodies, and if they obtain an intestinal permeability test, what should they do if they test negative for a leaky gut? Should one assume that the test is accurate and not provide any gut repair support? Well, part of this does depend on the person. For example, if someone has Celiac disease and has been eating gluten for numerous years, I usually would expect for them to have a leaky gut, and in this case I very well might bypass the testing and just put the person on a leaky gut protocol. But I have had people test positive for transglutaminase antibodies and shortly after receiving these results test negative on an Array #2 from Cyrex Labs. In other words, they had Celiac disease and were still eating gluten, yet tested negative for a leaky gut.
In this case I would still support the gut and recommend some things for gut repair. This is especially true if the person was experiencing gastrointestinal symptoms. But since a leaky gut doesn’t always cause GI symptoms, if someone has Celiac disease and tested negative for a leaky gut even though they were consuming gluten regularly at the time of doing the test, I almost definitely would tell the person to take some probiotics, L-glutamine, etc. In other words, I wouldn’t rely on the results of the test.
But how about if someone with Graves’ Disease or Hashimoto’s Thyroiditis doesn’t have Celiac disease, tests positive for elevated thyroid antibodies, yet tests negative for a leaky gut? Well, I usually will give the person some basic gut support, and I’ll still encourage the person to eat foods which can help heal the gut, such as fermented food, bone broth, etc.
The reason I decided to write this post is because even if a leaky gut isn’t present in ALL autoimmune conditions, it without question is very common in conditions such as Graves’ Disease and Hashimoto’s Thyroiditis. As a result, many people with these conditions will need to follow a protocol to help repair the gut. However, not everyone with positive autoantibodies who receives testing for a leaky gut will have a positive result. This is either due to these tests not being completely accurate, or it means that some people with autoimmunity don’t have a leaky gut. I do believe that no test is perfect, and therefore it is possible that these tests don’t always pick up an increase in intestinal permeability. I’m honestly not sure if a loss of intestinal barrier function is a necessary component for autoimmunity, but hopefully we’ll find out for certain in the near future.