What is gluten?

How can gluten be harmful?

What is gluten sensitivity?

What are the symptoms of gluten sensitivity?

How is gluten sensitivity diagnosed?

Can I have gluten sensitivity if screening blood tests for celiac sprue are negative or indeterminate?

Why is a stool test a logical test for gluten or other food sensitivity?

Do I have to be eating gluten to be tested?

Can I be tested if I am already on a gluten-free diet?

What is the role of genetic testing?

How do I know if I have intestinal damage due to gluten?

What is the difference between celiac sprue and gluten sensitivity?

Can I have gluten sensitivity if small intestinal biopsies are normal or only minimally abnormal?

Who should be screened for gluten sensitivity?

Why you should not wait for intestinal damage before going on a gluten-free diet

What test should I order for diagnosis of gluten sensitivity?

How do I place orders for multiple family members?

What is gluten?
Gluten is a protein contained in the grains wheat, barley, rye, and oats. It is a unique protein based on its structure that lends a doughy/elastic consistency to flours derived from these grains. This is why over the centuries, gluten-containing grains have come to be used so extensively in breads and other baked goods.Top

How can gluten, a protein from a naturally occurring foodstuff, be harmful?
First, it must be understood that the gluten-containing grains we eat today are actually domesticated and now genetically hybridized versions of what originally were wild grasses endemic to the Tigris-Euphrates river basin. Presumably, due to pressures from shortages of other foods, or ingenuity of ancient peoples, these grasses became a source of food and calories. Learning how to cultivate and farm these and other plants alleviated the pressures of the hunting/gathering lifestyle, paving the way for more abundant and readily available food, which in turn, paved the way for the more stable and populated Agrarian societies that followed. It is believed and seems sensible, that this shift to agriculture-based societies was responsible for the flourishing (note the word flour in flourishing) civilizations of Mesopotamia and Egypt that followed. Thus, wheat, barley, rye, and oats are genetic derivatives of wild grass, and therefore pose the possibility that eating a wild plant may possess some toxicity.

The nature of the toxicity, although to some extent stems directly from the chemical nature of gluten, is mostly due to a reaction that occurs by the immune system of individuals in possession of certain genes that recognize gluten for the foreign protein that it is and hence toxic. The immune system genes in control of this reaction are actually not rare, and may be present in up to 60% of Americans (based on my research). However, there are other, as of yet undetermined, genes that control whether or not a toxic reaction will occur, and further, whether and how much the reaction will result in damage to the intestine and other tissues. It is speculated that the structure of gluten may be similar to an infectious agent (for example a virus) and that is really why the gene is present in the immune system in the first place. It is even possible that the gene controlling reactivity to gluten is so common because millions of years ago it lent a survival advantage against dying from infections to those possessing it. Thus, having an immune system that recognizes gluten as a foreign, potentially toxic protein actually may be a sign of an immune system that is particularly sensitive and protective. Although this may portend protection against infections, the down side is that the same genes lead to more severe, longer lasting immune responses to foods, environmental allergens, and even the human body itself. The consequences of these reactions are food sensitivities (of which gluten sensitivity is just one), allergies/asthma, and autoimmune disease, respectively.Top

What is gluten sensitivity and how is it diagnosed?
Gluten sensitivity implies that there is an ongoing immune reaction to gluten in the diet, usually detected as antibodies against a subprotein of gluten called gliadin. Although recently these antibodies were looked for only in the blood and are found in 12% of the general American public, my research has revealed that these antibodies can be detected in the stool in as many as 35% of what are otherwise normal people (U.S. and International patents pending). If high risk patient populations are tested, or people with symptoms, the percentage usually exceeds 50%. It makes sense that the antibodies are more easily detected in the intestine because the immune system reaction to food is mainly a response occurring inside the intestinal tract. Thus, the end product of intestinal transit, stool, is the most logical (albeit more messy) place to look. This is the rationale of the new tests developed by EnteroLab to serve the testing needs of celiac patients. Top

What are the symptoms of gluten sensitivity?
Although there may be no detectable symptoms of the immune response to gluten, the typical symptoms people develop occur when the reaction begins to damage the intestines. The symptoms, resulting from malabsorption or improper digestion of dietary nutrients, include abdominal bloating or pain, diarrhea, constipation, gaseousness, or nausea with or without vomiting. It appears that acid reflux in the esophagus, manifesting as heartburn, may be a potential symptom as well. Other symptoms people experience include fatigue, joint pains, mouth ulcers, bone pain, abnormal menses in women, and infertility.Top

How is Gluten Sensitivity Diagnosed?
In recent years, testing for gluten sensitivity and celiac sprue usually is initiated with blood tests for antibodies against gliadin, the toxic subfraction of wheat gluten, or for an antiendomysial antibody that is produced against an enzyme present in the intestine and elsewhere in the body called tissue transglutaminase. These tests have revolutionized testing for celiac sprue because they allow for detection of the syndrome before extensive irreparable damage to the intestine, bones, and other tissues has occurred. Up until recently it was thought that nearly all patients with clinically important gluten sensitivity had these antibodies detectable in blood. However, recent studies, including my own, have shown that this is not true. In the early phases of the reaction, or especially when the disease is of a more mild variety, antigliadin and antiendomysial/antitissue transglutaminase antibodies may be absent from blood. Knowing that the immune reaction to gluten and other foods takes place inside the intestinal tract, we began testing the hypothesis that these antibodies may be present in the intestinal tract in gluten sensitive individuals, even if they are absent from blood. Extensive research has revealed that this hypothesis is true, and has resulted in the development of new methods for detection of gluten sensitivity, celiac sprue, and other food sensitivities (U.S. and International patents pending). This test has shown to be 100% sensitive for picking up celiac sprue in those so affected. This test is being offered at an affordable price by EnteroLab.Top

Can I have gluten sensitivity if screening blood tests for celiac sprue are negative or indeterminate?
The answer to this question is definitively yes. Originally screening tests for gluten sensitivity/celiac sprue consisted of blood tests against the damaging protein in gluten called gliadin (antigliadin antibodies). However, with heightened awareness of the possibility of gluten sensitivity in family members of diagnosed celiacs, or in people with syndromes associated with celiac sprue, it has become clear that not all people suspected of being immunologically intolerant to gluten have positive blood tests. This is problematic because these individuals are told outright that they are not gluten intolerant based on negative blood tests. Many times patients themselves are able to deduce that it is wheat that causes them to feel ill or have intestinal symptoms, but when blood tests are negative they are diagnosed with irritable bowel syndrome or sometimes "wheat allergy". It is not surprising to me that blood tests in the early phase of gluten sensitivity are negative. This is because the immunologic reaction to gluten begins and occurs inside the intestinal tract and not in the blood per se. For this reason, I had an idea about a year ago that these antibodies should be more frequently detected in the stool of gluten sensitive individuals rather than in the blood. This turned out to be the case based on extensive analysis of more than 500 normal people or people with various medical syndromes (including bonafide celiacs, patients with microscopic colitis, a form of colitis genetically and clinically related to gluten sensitivity, and patients with chronic diarrhea of unknown origin). Based on this research and its importance, I have brought this new test to the public directly via the internet from www.EnteroLab.com This new stool test can detect antigliadin antibodies in stool whether a person has symptoms or not. It is ideal for children who do not have to be stuck with a needle. Samples can be mailed from your home without having to go to the hospital or a doctor's office. Furthermore, you can decide if you want to be tested and do not have to beg a doctor to test you for gluten sensitivity.

Thus, because the antibodies produced as the result of gluten sensitivity are mainly secreted into the intestine rather than the blood, analyzing stool turns up many more positive tests than blood tests. It is only when the immune reaction has been present for long periods of time and/or the process is far advanced that antibodies are produced in quantities sufficient to leak into the blood.Top

Why is a Stool Test a Logical Test for Gluten or Other Food Sensitivity?
The immune cells present in the intestinal tract comprise the largest mass of tissue in the body assigned the function of protecting against foreign invaders. These invaders are present in the form of proteins called antigens. Although the intestine's immune cells probably evolved originally to ward off infecting organisms, in fact, their most frequent exposure to foreign antigens comes from food. One of the first lines of defense against foreign antigens (food or infections) is the secretion of a special antibody called secretory IgA into the intestinal lumen (i.e., the hollow center of the intestine). Here, these antibodies bind the antigen by a sort of lock and key recognition mechanism, in an attempt to neutralize the antigen so that it cannot enter the body. Because these antibodies do not get reabsorbed after entering the intestinal tract, they travel all the way through the intestine where they can be recognized in the stool. This is the rationale for the new gluten and other food sensitivity testing methodology invented and offered by EnteroLab (U.S. and International patents pending)Top

Do I have to be eating gluten for a gluten antibody test to be positive?
Because production of antigliadin antibodies is under genetic control, your body continues to make these antibodies for an extended period after gluten is removed from the diet, albeit, in lesser quantities the longer gluten is removed from the diet. Research has shown that these antibodies continue to be produced at lower levels for months, even 1-2 years after gluten is removed from the diet. Stool tests can continue to detect these low levels of antigliadin antibody produced in the intestine over this 1-2 year period (and longer if there is still small amounts of gluten in the diet, even hidden gluten); tests for antigliadin antibody in the blood routinely become negative after 3-6 months on a gluten-free diet. Top

If I am already on a gluten-free diet, do I have to return to eating gluten to be accurately tested for gluten sensitivity using the stool test?
Although it has been stated that a person must be eating gluten to be able to detect antibodies to gliadin in blood, we have found that this is not true for our stool tests (and other researchers have found the same when sampling upper intestinal contents with tubes). Because the stool tests (but not blood tests) can find low levels of antigliadin antibody produced in the intestine, we actually recommend that you be tested on your current diet, that is, gluten-containing or gluten-free. The amount of antibody being produced at any given gluten intake will be more meaningful if it reflects your normal condition rather than an artificially created condition by reintroducing gluten (if you have been off of it for a time) or trying to eat gluten in excess. Furthermore, even though a person removes obvious sources of gluten from the diet, there continues to be the potential of hidden gluten in less obvious food or drug sources (such as food additives, medicines, lotions, etc.), or when eating outside the home. Thus, it is possible that the test still may turn up positive for this reason.

Our recommendation then is simply to eat what you are currently eating, or whatever you think is best for you right now. There is no need to introduce the food being test for in any amount, and especially not in large amounts which could make you ill. If you have been off gluten for short periods, the results will be very close to those if you never had removed gluten from the diet. For people who have been gluten-free for longer than 1-2 years, it is actually best to remain gluten-free for the stool test, and to also rely on the gene test to aid in the diagnosis (see next section).

Thus, it is better to test on the current diet before adding the unreliable variable of a one to two week gluten challenge. It varies in different people how they or their immune system will react to gluten, and how long it would be required to eat gluten to make tests positive (as they once may have been before starting the diet). There are no guarantees that a truly gluten sensitive person will have positive tests after a short 1-2 week gluten challenge anyway, even if they get symptoms from it.

Here are the potential scenarios of stool and gene test results if testing is performed on a low gluten or gluten-free diet (rather than doing a gluten challenge).

Scenario 1
Because the stool test is much more sensitive than the blood tests, and the antibody can be produced for years after removal of gluten from the diet, the stool test may well be positive despite being on a reduced or restricted gluten diet. The gene test (which we recommended as a complementary test to the stool testing, especially when someone has been off of gluten for long periods of time because the gene test is never affected by the diet) likely will support the positive results.

Scenario 2
The stool test is negative (because they have limited or stopped gluten for a long period like many years) but the gene test is positive. This data is useful because it tells you at least that antibody production to gluten has stopped on the gluten-free diet. And the positive gene test or potential improvement you may have experienced after beginning your gluten-free diet are supportive that you are gluten sensitive. If the gene test is negative, it is still remotely possible to be gluten sensitive.

Alternatively, if you choose to do a gluten challenge at the outset (again which we do not recommend) and the test is negative, it may be so because damage and antibody production has not yet been initiated. And you do not get the benefit of a comparison of what your antibody levels were when gluten was out of the diet. The comparison itself before and after gluten can be helpful, and is definitely more meaningful than testing after a short time on gluten after being gluten-free for an extended period.

Thus, I recommend testing in the stable gluten-free condition first then in the variable gluten-challenge condition only if necessary.

One final note. Sometimes people experience dramatic improvement of symptoms and feeling of well-being after beginning a gluten-free diet. If the improvement to health was dramatic following removal of gluten from the diet, then this in and of itself is a positive diagnostic test (and perhaps the ultimate test).Top

What role does genetic testing play in the diagnosis of gluten sensitivity?
Currently, tests are available to detect the genes that control the immune system's reaction to gluten. These genes are called human leukocyte antigens or HLA. There are several types of HLA genes within each person. It is a particular type called HLA-DQ that is most useful in the assessment of the probability that a person may be gluten sensitive. The reason gene testing assesses probability rather than disease itself is because some people have the genes for gluten sensitivity but have no detectable evidence of the immune reaction to gluten or have no symptoms. In such people, gluten sensitivity is still possible but the probability (or in other words the chances or the odds) is lower than in a person who may be having symptoms attributable to gluten or that has antibodies detected. HLA testing is most useful when there is diagnostic confusion about whether or not a person is gluten sensitive. Such confusion often stems from one of the following: atypical intestinal biopsy results, the presence of associated diseases (such as microscopic colitis) that may mask the expected improvement of symptoms when gluten is withdrawn from the diet, negative tests for gluten antibodies in the midst of suggestive symptoms or signs of gluten sensitivity or celiac sprue (see the paragraph below to understand the difference), or when there are no symptoms at all and the person or the doctor can hardly believe that gluten sensitivity is really present. Other situations that HLA testing is useful is when a person is already on a gluten-free diet, and for testing family members (particularly children) for the odds that they have or will develop gluten sensitivity.Top

How do I know if gluten sensitivity has damaged my intestines?
If intestinal symptoms are present in the face of a positive antibody test to gliadin, it is likely that some damage is present. Although traditionally, doctors have relied on a biopsy of the upper small intestine to prove or disprove this, it is now known from medical research (including studies I have conducted) that the damage may be imperceptibly subtle, possibly to the extent of being invisible to the microscope. Thus, tests assessing the function of the intestine rather than how it looks under a microscope are playing a more important role in this field.

For more than 50 years, the primary method used to assess for the presence of small intestinal damage and nutrient malabsorption in patients with celiac disease has been a 72-hour quantitative stool collection. However, because this method requires that patients accurately collect all the stools they pass for 3 days (missed stools lead to falsely low results), the test is logistically difficult for medical centers unaccustomed to the procedure, and the voluminous specimens usually are abhorred by patients and laboratory technicians. It poses obvious problems for children who cannot or will not collect all their stools, as well as for patients with chronic diarrhea, who may have bowel movement frequencies reaching 15 or more per day and/or fecal volumes as high as 2 or 3 liters per day. For these reasons, physicians evaluating patients with suspected or proven gluten sensitivity often avoid tests for intestinal malabsorption altogether.

Recently, EnteroLab researchers have developed a new method for quantitating fecal fat excretion that requires collection of only a single stool specimen. Development of this method was based on the fact that as more fat is malabsorbed, the fat globules in stool become more numerous and larger. As reported in the April 2000 issue of the American Journal of Clinical Pathology in an article entitled "A New Method of Quantitative Fecal Fat Microscopy and its Correlation with Chemically Measured Fecal Fat Output", I and Frederick Ogunji Ph.D. tested 180 patients and found a highly statistically significant linear correlation between quantitative fecal fat microscopy (the new method) and chemically measured fecal fat output (the old method). We also showed that microscopic analysis of just one stool gives comparable results to analysis of an entire 3-day collection. Thus, a dedicated quantitative analysis of one stool under a microscope can detect the rise in fecal fat due to intestinal malabsoprtion (or pancreatic maldigestion) as accurately as 3-day stool collections, making these multi-day collections a thing of the past for most patients.

Patients with gluten sensitivity should be evaluated for nutrient malabsorption because if present, this means there is small intestinal damage and institution of a gluten-free diet is imperative to prevent osteoporosis and other nutrient deficiency syndromes. Furthermore, a test at the time of diagnosis serves as a baseline to be compared to later if needed.

This new stool test for intestinal malabsorption and other celiac-testing is available for order online from EnteroLab.Top

What is the difference between celiac sprue and gluten sensitivity?
Gluten sensitivity implies that a person's immune system is intolerant of gluten in the diet and is forming antibodies or displaying some other evidence of an inflammatory reaction. When these reactions cause small intestinal damage visible on a biopsy, the syndrome has been called celiac sprue, celiac disease, or gluten sensitive enteropathy. (Nontropical sprue and idiopathic steatorrhea are other terms that have been used for this disorder in the past.) The clinical definition of celiac sprue also usually requires that there is clinical and/or pathologic improvement following a gluten-free diet.

In the past, celiac sprue could only be diagnosed after somebody developed certain symptoms like diarrhea, weight loss, or growth failure in children. A biopsy would be performed and if abnormal and typical of celiac sprue, and if a gluten free diet brought resolution of diarrhea, weight gain, or growth, only then would a diagnosis of celiac sprue be made. However, recent advances in diagnostic screening tests and application of these tests to people at heightened risk or to general populations have allowed detection of celiac sprue, sometimes even before damage to villi has occurred. This latter scenario is often called gluten sensitivity. Top

Can I have gluten sensitivity if small intestinal biopsies are normal or only minimally abnormal?
Although by definition a normal small bowel biopsy rules out celiac sprue, it does not rule out gluten sensitivity. Although asymptomatic people with gluten sensitivity may have normal or near-normal biopsies, so too may people with symptomatic gluten sensitivity. This has been reported in the medical literature (called "Gluten Sensitivity with minimal Enteropathy" or "Gluten-Sensitive Diarrhea without Celiac Disease". Furthermore, even though such people's intestines appear normal under the microscope, up to one half already have nutrient malabsorption, a major contributor to osteoporosis and malnutrition, attesting to the fact that microscopic analysis of intestinal biopsies is an insensitive way of assessing function and immunologic food sensitivity. However, because there is still a virtually universal reliance on small bowel biopsies to diagnose gluten intolerance, most asymptomatic or symptomatic gluten sensitive people (based on screening tests) will not be diagnosed correctly or be instructed to follow a gluten-free diet even though symptoms may resolve completely.Top

Who should be screened for gluten sensitivity?
Because research has shown that as many as 30% of all Americans may be gluten sensitive, and that 1 in 225 have a severe form of this sensitivity causing the intestinal disease called celiac sprue, a case can be made that everyone in America should be screened for gluten sensitivity. However, there are people with various risk factors or diseases that are at greater risk of developing gluten sensitivity who should undoubtedly be tested. These include: