What's the deal with gluten?

What is gluten?

Gluten is a collection of proteins found in wheat, barley, and rye.  In genetically susceptible individuals, ingestion of gluten initiates an abnormal immune response resulting in inflammation of the small intestine, or Celiac disease (CD).

CD is not an allergy or an intolerance. The immune response in CD is not the same as that seen in peanuts or other food allergies. Such allergic reactions are typically rapid onset and cause a release of histamine, which can result in swelling of the skin, lips, hands, face, eyes, upper respiratory tract, and sometimes violent vomiting or diarrhea within minutes or hours of ingestion. CD requires chronic exposure to gluten, and individuals with CD need to completely avoid gluten ingestion in order to heal from the disease.  Healing can take up to a year. Common symptoms of CD include watery diarrhea, bloating and gas, weight loss, specific skin conditions, neurologic conditions, B12, and iron deficiencies. 

CD is common, found in approximately 1% of the population. However, it is less common than irritable bowel syndrome (1 out of 7), but more common than Crohn's disease (1 out of 500-1000 patients).
 

How does gluten affect the non-celiac patient?

Many people have found that removing gluten from their diet (by avoiding wheat) improves their food related symptoms. Patients may feel less full, less bloated, less gassy, less fatigued, or have reduced episodes of diarrhea. Clinically, this has been called non-celiac wheat sensitivity (NCWS). It is diagnosed after careful exclusion of celiac disease by a gastroenterologist. 

While most people assume gluten triggers bloating and discomfort, there are many other substances in wheat such as wheat sugars and fiber that are the more likely culprits of these symptoms in the non-celiac patient. Clinical studies have shown that the NCWS patient is actually responding adversely to Fructans, which are a polymer or long chain of fructose molecules found not only in wheat but also cabbage, shallots, broccoli, onions, garlic, and asparagus. Fructans belong to a group of sugars called FODMAPs.

What are FODMAPs?

FODMAP stands for Fermentable Oligosaccharides Disaccharides 
Monosaccharides and Polyols. These are carbohydrates or sugars of varying shapes and sizes that are either indigestible or poorly absorbed. FODMAPs bypass the small intestine and instead are fermented in the colon by bacteria, which results in the production of hydrogen and methane gas (i.e. flatus, bloating, abdominal distention, pain), short chain fatty acids, and osmotically active metabolites that pull water into the colon (i.e. diarrhea). Fructans are a type of oligosaccharide (long chain sugar). Lactose, a disaccharide sugar in milk, is another common FODMAP. Love your avocados but get gas? Well, thats sorbitol, a polyol.

How is Celiac disease or NCWS diagnosed?

Initially a blood test is performed, which measures levels of circulating antibody markers. Those that have excluded all gluten from their diet prior to seeing a doctor will need to re-introduce it for 6 weeks with at least 2 slices of bread a day before considering testing. This is because the level of the CD markers decline while on a gluten free diet. If markers are positive, confirmation will be needed by obtaining biopsies of the small intestine during an upper endoscopy

If patients test negative for celiac disease, NCWS is diagnosed when symptoms resolve after removing wheat from the diet. However, an important difference is that an NCWS patient may be able to tolerate more moderate amounts of wheat than the celiac patient.

What markers are most sensitive and specific?  

In the presence of normal serum IgA levels, IgA anti-Tissue Transglutaminase antibody tends to be most sensitive and specific. Others have lower positive predictive values (chance of a positive being true positive). 

Is there a genetic test? 

Yes and no. The test is only useful to exclude CD. Companies like 23andMe are including these genetic markers in their testing panels (HLA DQ2/DQ8). However, these genetic markers are not sufficient to diagnose CD. Rather, their absence helps to exclude it as nearly all CD patients carry them while 40-50% of the non-celiac population also carries them. Testing negative for the genetic markers completely excludes CD.

Genetic testing can be utilized when results of conventional testing are ambiguous, or their is a high suspicion despite conflicting test results (i.e. positive markers, negative biopsy).