Celiac Disease and Gluten Sensitivity
Celiac disease, also known as gluten intolerance, is inflammation of the small intestine caused by exposure to gliadin—a component of gluten, which is a protein found in wheat, barley, rye, and (to a lesser extent) oats. (Oats do not contain gluten by nature, but they can become contaminated in facilities that process the other grains.)
1 in 133 people, or approximately 3 million Americans, currently have celiac disease.
Celiac disease is 2-3 times more common in women than in men.
Varies depending on sensitivity.
Symptoms
When does celiac disease show up for most people?
The average age of diagnosis in the US is about 40, though there is a peak around age six and another in the fourth and fifth decades. Celiac can show up in genetically predisposed children once the environmental trigger (exposure to gluten) has occurred, so historically it was considered more of a childhood disease.
Celiac also presents differently depending on age. In children, diagnosis may be pursued due to diarrhea, malnutrition, failure to gain weight, or delayed puberty. Adults more commonly find out during a workup for IBS, or possibly through investigation into reasons for anemia or low bone density. Age of diagnosis has shifted to include more older adults, and there is increased awareness that symptomatology can vary.
What are the most common celiac disease symptoms?
Recurrent or chronic diarrhea, abdominal pain, bloating, foul-smelling stools, and constipation are the most common gastrointestinal symptoms.
Do people always have GI issues with celiac disease?
No, they can also have what we call extraintestinal symptoms (symptoms beyond the intestines). Sometimes people present with a characteristic rash, joint pains, or even a routine blood test revealing elevated liver enzymes—all these symptoms are more common in adults.
Most people do have GI symptoms, but the spectrum of severity is relatively broad. Around 60-70% of those who have celiac are undiagnosed, likely because celiac can have these non-GI presentations—like fatigue or coordination and balance problems.
Causes
Why do people get celiac disease? Is it purely genetic or are there other factors involved?
There is a relatively strong genetic predisposition. First-degree relatives of those who have celiac have between a four and 15 percent chance of also having celiac disease. Since the general population’s risk is a bit less than one percent, we're looking at about ten times that risk.
That said, genetics alone don't explain the whole story. 30% of the population carries the genes seen in all celiac sufferers (HLA DQ2/DQ8), but only 3% of those carrying the at-risk gene variants develop celiac.
Infections have been theorized to be among the triggers, and a prospective study published in 2019 demonstrated a possible causative association with enterovirus (a common virus that causes gastrointestinal symptoms), but not adenovirus (another prevalent virus). Duration of breastfeeding and age of dietary gluten introduction are two other possible contributing factors.
Can you touch on the immune component in celiac disease?
The immune activation process is thought to occur in two different layers of the small intestine by mechanisms involving both the innate and adaptive immune system.
The epithelial lining of the intestine—the innermost layer where nutrient absorption occurs—is infiltrated by lymphocytes (a type of white blood cell), causing damage to that single cell layer.
A deeper layer of the intestine, called the lamina propria, is the location of a more complex interaction between gliadin—a tissue enzyme called transglutaminase—and genetic material. An inflammatory cascade occurs that damages the tissue, thus blunting the fingerlike projections (villi) that are responsible for the small intestine’s massive surface area.
What about the microbiome?
Recognition of the complexity of immunological individuality has led to increased research of the gut microbiome, its determinants, and its role in widespread communication within our bodies.
The microbiome aids in digestion and immune system development, both of which clearly influence development of celiac.
There is also a new study examining factors such as route of birth (vaginal versus cesarean), breastfeeding, food introduction windows, and other microbiome determinants that will hopefully move us closer to explaining why only some genetically predisposed people develop celiac.
This research area builds on trends that we have seen over time related to the hygiene hypothesis, which proposed that hyper-sterilization of our environment can have deleterious impact on our body ecology.
Diagnosis
How do you diagnose celiac disease? Is a test necessary?
For most children and adults, the best way to screen for celiac disease is with the tissue transglutaminase IgA antibody (tTG-IgA), plus total IgA antibody in order to ensure that the patient generates enough of this antibody to render the celiac disease test accurate.
The extent of testing needed depends on the patient's age and those initial blood test results. Children typically have higher antibody levels, which can confirm diagnosis. In adults, a follow-up endoscopy and biopsy to confirm diagnosis is recommended in more than 50% of cases, as antibody levels often are not as significantly elevated.
How accurate are the tests? Are there factors that could lead to false positives or false negatives?
Tissue transglutaminase IgA antibody testing is about 98% sensitive. Another test sometimes utilized in this workup is HLA (human leukocyte antigen) testing. The HLA DQ2/DQ8 genetic test is much more helpful for determining who does not have celiac than who does, since 30% of the population is positive for the HLA subtype that predisposes to celiac. If someone is negative, however, it essentially rules out celiac.
Do we know why there has been an increase in cases over the last twenty years?
Awareness about celiac has certainly improved, so more people are being diagnosed earlier in their course, though the average length of time to diagnosis is six-to-ten years from the start of symptoms.
It’s often speculated that something has changed with the grains we consume, but grains don't actually have substantially more gluten than a century ago. All autoimmune diseases are more common now than before, and it’s suspected that this increase in prevalence might be related to changes in our immune systems, not changes in the grain itself.
Some gluten sensitivities are not as severe when people travel to other parts of the world. Is this true for celiac?
Most gluten-sensitive people in America are also gluten-sensitive elsewhere, so people with celiac disease should avoid wheat, barley, and rye when traveling.
There are several possible variables that determine someone’s immune response to gluten, including species, cultivar, and growing conditions of the grain, as well as processing methods. But if there were significantly less gluten in grains from abroad, we might expect less celiac disease abroad. And what we've seen is that prevalence is pretty consistent throughout the rest of the world, though it’s somewhat higher in parts of north Africa and lower in parts of Asia.
Treatment
Beyond eliminating gluten, are there other important aspects to treating celiac?
A diet free of gluten is the treatment for celiac disease, currently. However, there is a minority subpopulation that will continue to have symptoms despite elimination of gluten. Therefore, in the time period shortly after diagnosis, it may be important to actively replenish lost nutrients, like iron or B vitamins.
In the weeks and months following diagnosis, resolution can be measured by decreased antibody levels, change in the appearance of the intestinal lining, and normalization of liver enzymes or other abnormalities that were detected at the time of diagnosis. Clinicians should also stay on high alert for conditions more common in people with celiac disease, such as autoimmune thyroid disease and type 1 diabetes.
What are the consequences of untreated celiac disease?
One category of consequences is connected to nutrient malabsorption from inflammation due to blunting of villi in the inflamed small intestine. This includes anemia (from iron or folate deficiency), peripheral neuropathy (due to B vitamin deficiencies), and other sequelae of suboptimal nutrition. Perhaps unsurprisingly, infants born to mothers with celiac disease are at risk for low birth weight.
There are other consequences that are not directly linked to the gut’s role in nutrient assimilation, but rather to its ability to screen proteins through the immune system, 80% of which lives in the small intestine. Specifically, gut inflammation may cause intestinal permeability, which allows undigested proteins to move from the intestines into the bloodstream through protective gates called “tight junctions.” This can lead to extraintestinal symptoms and other deleterious health effects.
Gluten Sensitivity
If people don’t have celiac disease, can they still have gluten sensitivities?
Yes, there is a condition called non-celiac gluten sensitivity (NCGS), sometimes known as non-celiac wheat sensitivity (NCWS), which is an emerging area of research interest.
The mechanism is not totally understood, as this group of people may be sensitive to gluten, non-gluten components of the grain, or both. It is now established that this population of people will test negative for celiac disease, but do have intestinal inflammation. Alessio Fasano, MD is one of the most active researchers to follow in this field.
What are the most common symptoms of non-celiac gluten sensitivities?
As with celiac, the intestinal symptoms are probably more recognized than the extraintestinal symptoms. The extraintestinal symptoms include many of the same as celiac: headaches, mood disruptions, fatigue, brain fog, joint pains, etc. We don’t have strong statistics yet about increased risk of other conditions, like autoimmune disease.
Are there good tests for gluten sensitivity?
Currently, there aren’t great biomarkers for this. Dietary elimination of gluten for a few weeks is the best way to determine tolerance.
Reducing Gluten
Do people with celiac and other gluten sensitivities usually feel better immediately after stopping gluten?
Response to gluten elimination (adopting a celiac disease diet) can depend on the target symptoms. Abnormal stools or gas could improve within days, whereas something like fatigue often takes several weeks to improve. The timeline is highly dependent on which physiological processes are involved.
Are there reasons for people who don’t have celiac or a gluten sensitivity to eat less gluten?
That is a hard question, and depends on who you ask. Theoretically, people who tolerate gluten have no reason to worry. There is an argument to be made that gluten-containing foods can be over-consumed and might be better partially replaced by other, more nutrient-dense carbohydrate sources, like vegetables.
A further justification some people use for avoiding gluten is related to the pesticides which may have been used on the grains, as some people prefer to dramatically limit their exposure.
Useful Links
An information and service resource for patients (Celiac Disease Foundation)
Educational information on celiac (Beyond Celiac)
Harvard’s multicenter celiac research program (Harvard Medical School Celiac Research Program)
A comprehensive take on celiac disease trends (The Celiac Surge)
Connect with our physicians
Jamila Schwartz, MD and Andrew Cunningham, MD are both members of the Galileo Clinical Team. Connect with one of our physicians about Celiac Disease and Gluten Sensitivity or any of the many other conditions we treat.