Celiac Disease and Gluten Sensitivity - Should we be worried?

Introduction to Celiac Disease and Gluten Sensitivity

Consumption of wheat has increased dramatically over the last decades.^[1] Wheat was once thought to be an important part of a healthy diet, but now is seen as a potential health threat for many individuals. Gluten is a food component found in wheat, rye, barley, and cereals. More specifically, it is a protein complex that is formed by gliadin and glutenin, typically used in processed foods as a stabilizing agent. Celiac disease (CD) is a complex chronic immune-mediated disorder whose gastrointestinal symptoms are triggered by eating gluten. Alternatively, there is non-celiac gluten sensitivity (NCGS). People who have NCGS also have symptoms when they ingest gluten, but without the typical diagnostic criteria for CD, which we will discuss shortly. These 2 conditions should be clearly separated from wheat allergy. Wheat allergy occurs when there is an anaphylactic reaction to gluten, with the presence of IgE.

Our focus here will be on CD and NCGS. In a very large study in Italy with 37 specialist centers participating, it was found that 3.2% of people had NCGS.^[2] The average patient's age was 38 years old and there were 5 times as many who were female. They identified CD in 2.8% of the participants. Other frequent findings included irritable bowel syndrome, allergies, and autoimmune diseases. Lab tests in those affected also showed low levels of ferritin (iron stores), folic acid, and vitamin D. This means that CD and NCGS can put people at risk for nutrient deficiencies.

Other studies have found wide variations in prevalence of NCGS, for example sometimes as high as 13%, depending on how it is being assessed (questionnaire, clinical encounters, etc.^[1] As an additional difficulty in identifying NCGS, people who opt to consume a gluten-free diet (GFD) may not have readily identifiable clinical signs and symptoms. A trial introduction of gluten that elicits symptoms may help to lend credibility to a NCGS assessment. As we will see in this article, the key treatment for CD and NCGS is a GFD. GFDs are becoming extremely popular amongst health-conscious communities and the market for gluten-free products is expanding rapidly. There are even events such as the Gluten Free Expo that are fully dedicated to helping people find gluten-free alternatives. What is also of interest is that several people without CD or NCGS opt to go gluten-free because they appear to derive health benefits. This begs the question: should we all be incorporating the GFD?

Pathology of Celiac Disease

CD is a multifactorial condition in the sense that it may take more than one factor to occur for the disease to manifest itself in an individual. CD has a strong genetic component with multiple contributing genes.^[3] Usually it is the HLA genes that are considered primary risk factors. Having these genes does not guarantee someone will have the disease, so some other trigger is likely to activate the disease process (such as exposure to gluten!). Also, there is a small proportion of people who have CD who do not have these genes. Recent studies have identified the possible role that intestinal microbiota may play in the development of CD. For example, a comparison between healthy, diseased, and treated celiac adults has shown a lower number of Streptococcus spp. and Prevotella spp. families in untreated celiac adults.^[4] It's possible that the bacterial populations have been modified by changes in the intestinal environment caused by active CD. It's also been shown that the bacterial species in the feces and duodenum of children with active and treated CD had a lower ratio of harmless to harmful bacteria. Other factors that can play a role include the time when gluten is introduced into the diet of a child. One study found that if gluten exposure is delayed by 6 to 12 months, it can have a positive effect on gluten tolerance.^[5] In particular, it was protective in those that were genetically susceptible to CD.

Recent studies have shown that the colonization of the gastrointestinal tract is important when discussing in relation to autoimmune disorders and food-related conditions.^[6] There may be interactions between the intestinal bacteria and the immune system in the direct differentiation of pro-inflammatory and anti-inflammatory immune cells. Certain strains of bacteria (Bifidobacterium) are able to suppress and reverse proinflammatory effects.^[6] For this reason, these probiotic strains are often suggested as part of the treatment of CD. Interestingly, it is also possible that gluten intolerance could be triggered by viruses or bacteria that actually mimic gluten proteins. The body then reacts with an autoimmune response that can continue after the initial infection has cleared. Due to all the possible causes and the complex interactions with the gastrointestinal system, it is easy to see why having a few of these risk factors may be enough to cause NCGS, without causing full-blown CD. Also for this reason, palliative therapies for both conditions can overlap significantly.

Diagnosis

When it comes to diagnosing CD, there are a number of tests that can be used. Symptoms may help dictate which tests to use, but if the individual is already consuming a GFD, many of the tests lose their utility. The reason for that is that the antibody levels will decrease and so they may not be detected with lab tests at a later date. To confirm a diagnosis in someone who is consuming a GFD, gluten would have to be reintroduced prior to testing.^[7] Blood tests are usually the first lab tests that are done. Antiendomysial antibodies of IgA is one example of a blood test that is used and can detect CD with a high degree of specificity, but there exist other similar ones. Because the blood tests do not provide 100% certainty, it is usually recommended that any positive results are followed-up with more invasive imaging (or biopsy). In particular, endoscopies and intestinal biopsies can be used. Sometimes even if the blood test comes back negative, the doctor may recommend further testing. Biopsy is the gold-standard test for diagnosis of CD.^[8]

The diagnosis for CD is much more clear-cut than for NCGS. One issue with NCGS is that it is not even clear exactly how it should be identified. In the large Italian study we discussed earlier, the authors used a 60-item 'yes or no' questionnaire, but ended up deciding clinically.^[2] The NCGS population reports experiencing problems with wheat or gluten ingestion, but will test negative for specific tests used to diagnose CD. In one study that attempted to identify and effectively describe NCGS, they found that there were a variety of different causative processes and varying clinical histories.^[9] They only reached NCGS diagnosis by excluding both CD and wheat allergy. They found that the most useful indicators were reports of gastrointestinal symptoms with gluten ingestion that improved while on a GFD. In addition, they found that the chances of having NCGS increased if there was a history of food allergies in infancy, atopy, or increased IgG antigliadin antibodies.

Treatments: GFD and Probiotics

As we've discussed, the first-line treatment for CD and for NCGS is a lifelong GFD. There are no prescription drugs that prevent the autoimmunity that occurs as part of these conditions when gluten is present. When followed very strictly, the intestines heal, all symptoms resolve, and other health parameters improve. For example, CD is associated with diabetes, Addison's disease, thyroid disorders, liver disorders, arthritis, and skin conditions.^[6] When it comes to autoimmune disorder, there is a body of research identifying that exposure to gluten is related to a higher prevalence. There is evidence that a GFD is protective. Because of the way the immune system functions, some have suggested that autoimmune diseases can be reverted in childhood by instituting a GFD, but not in adulthood.^[6] However, the GFD is difficult to adhere to and failure to comply can cause relapse. It is possible that some individuals are more sensitive than others. Some individuals may need to be 100% strict, while others may be able to tolerate very small amounts of gluten without experiencing symptoms or relapse.

The other therapy we touched on earlier was probiotics. Biopsies from treated celiac children have demonstrated that a GFD lasting 2 years or more can restore the intestinal microbiota completely. It is possible that certain strains of bacteria like Bifidobacterium are able to suppress and reverse proinflammatory effects and may speed up recovery rates. They may also help the immune system become more tolerant to small amounts of gluten, so that individuals who choose to initiate GFDs do not have to be extremely strict. In terms of maintaining overall health, it may be wise to also address some of the possible consequences of CD. For example, if CD patients are at greater risk for low levels of iron, it may be wise to check iron levels routinely and supplement if necessary. Similarly, it may be wise to supplement with Vitamin D and folic acid to protect against possible depletion. Overall, it may not be necessary to be overly worried about gluten. The GFD has the ability to completely reverse CD and NCGS. The spectrum of sensitivity is quite varied and since a GFD is virtually without risk, it may be worthwhile for all individuals to try it at some point to see if benefits are obtained. After all, the number of people who don't have CD or NCGS or wheat allergy, but derive benefit from GFD seems to be increasing.