Uncovering the truth about celiac disease and non-celiac gluten sensitivity

In the past 20 years, there has been a real controversy over whether or not non-celiac individuals benefit from a gluten-free diet, according to Alessio Fasano, MD, at the 2018 Institute for Functional Medicine (IFM) Annual International Conference in Hollywood, Florida.

Recently, more people are saying everyone should eat a gluten-free diet to prevent inflammation. When asked who they think should adopt a gluten-free lifestyle, no session attendees thought it should be limited to those with celiac disease, and a handful thought everyone should eliminate gluten from their diets. However, the majority of session attendees felt “somewhere in the middle” was most appropriate, which Fasano echoed throughout his talk.

According to an online interview with users ages 18 and older who eat gluten-free foods, the majority, 50 million, embrace a gluten-free diet (GFD) because they feel it is healthier. Approximately 24 million eat a GFD to lose weight, 9 million to resolve gastrointestinal issues, 7 million to resolve gastrointestinal conditions, and 400,000 because they have been diagnosed with celiac disease.

GFD consumers can be broken down in to two categories, medical necessity and no medical necessity. Those in the “medical necessity” category have either a wheat allergy or celiac disease, which is autoimmune-based. The “no medical necessity” group do not have celiac disease, but have a gluten sensitivity.

“When people hear “diet,” they hear “weight control,” but that’s not always the case,” said Fasano, who clarified that most gluten-free products can make people gain weight. 

Gluten “glues” things together and makes food more palatable, he said. When the gluten is removed, it is replaced by fat and sugar, and is therefore highly caloric. If an individual is naturally gluten-free, it can help manage weight, but loading up on gluten-free substitutes does not lead to weight loss.

In a 2017 article in the Journal of the American Medical Association, Fasano and a team of researchers concluded that celiac disease and non-celiac disease are common. Although both conditions are treated with a gluten-free diet, distinguishing between celiac diseases and non-celiac gluten sensitivity is important for long-term therapy. Patients with celiac disease should be followed up closely for dietary adherence, nutritional deficiencies, and the development of possible comorbidities, researchers say.

Mucosal events that trigger a gluten response include increased permeability, gut inflammation, restructuring of intestinal mucosa, and enhanced neutrophil recruitment. Innate immunity is common to both conditions, which adaptive immunity is specific for celiac disease pathogenesis, says Fasano.

Celiac disease is a unique model of autoimmunity because there is so much information available. It is the only autoimmune disease in which specific MHC class II HLA, DQ2 and/or DQ8, are present for more than 95 percent of patients. The auto-antigen, tissue Transglutaminase, is known, the environmental trigger, gluten, is known, and elimination of the environmental trigger leads to a complete resolution of the autoimmune process that can be reignited following re-exposure to gluten.

Genetics plus the environment is what ultimately determines who will develop celiac disease. There are 55 genes related to celiac disease. The most consistent genetic component depends on the presence of specific MHC class II HLA, DQ2 and/or DQ8, genes. Other genes, not yet identified, account for 60 percent of the inherited component of the disease. HLA-DQ2 and/or DQ8 genes are not necessary, but not sufficient for the development of the disease. However, each other gene identified so far contributes only for a fraction of a percent to celiac disease genetics.

In recent years, celiac disease prevalence has skyrocketed from 21 percent in the mid-1970s to 93 percent in the early 2000s. According to Fasano, there are a few things driving this epidemic, which have historically included the quality of gluten in our diets, the quantity of gluten in our diets, the timing of gluten introduction, breast feeding, maturity of gut functions influencing antigen trafficking and handling (GALT, PRRs, mucous production, and barrier function), and changes in microbiome composition.

New research shows that the “window of tolerance” concept is not supported. Breast feeding in general or introduction of gluten while breast feeding showed no protective effect for infants at-risk for celiac disease. Early introduction of gluten traces to induce tolerance was not successful, nor was delaying the introduction of gluten to at-risk infants. Gastrointestinal infections during the first year of life seem influential in increased risk of celiac disease onset. High-risk HLA profiles seem to be the most influential factor predictor of increased risk of celiac disease onset. The research points to changes in microbiome composition as a primary driver in increased celiac disease occurrences.  

However, for gluten-related disorders, the quality and quantity of gluten are the driving factors. Gluten is an evolutionary divergence of oats, barley, rye, and the diploid wheats. With the agricultural revolution and development of genetically modified or engineered grains, wheat today looks much different than it did even 100 years ago. When it comes to quantity, populations today are actually consuming less gluten. Further, a growing body of research shows that gluten cannot be digested by the body.

Fasano posed some key questions about non-celiac gluten sensitivity. Though a number of celebrities, from Oprah to Angelina Jolie, tout a gluten-free lifestyle as their key to weight loss success, many people question whether non-celiac gluten sensitivity exists. Further, practitioners don’t know how it is diagnoses, if it is synonymous with irritable bowel syndrome, if FODMAPs trigger a non-celiac gluten response, or if gluten triggers a non-celiac gluten response or symptoms. 

Based on extensive research, Fasano offered his definition of gluten sensitivity: cases of reaction to ingestion of gluten-containing grains in which both allergic and autoimmune mechanisms have been ruled out. The diagnosis is based on exclusion criteria and is triggered by ingestion of gluten-containing grains. When testing for gluten sensitivity, practitioners may find negative immune-allergy tests to wheat, negative celiac disease serology, and negative duodenal histopathology. There is a possible presence of biomarkers of gluten immune-reaction and of clinical symptoms that can overlap with celiac disease or wheat allergy symptomology. Resolution of symptoms can be achieved following implementation of a gluten-free diet and relapse after exposure to gluten-containing grains.

While there is overlap with irritable bowel syndrome, FODMAPs, and other gastrointestinal issues, Fasano encourages practitioners to be persistent and work closely with patients to identify the root of their symptoms.

“If you don’t question yourself, you are not a good practitioner,” he said. “You aren’t here to prove yourself right—you’re here to change the quality of life for your patients.”

Editor’s note: This article is part of Integrative Practitioner’s live coverage of the Institute of Functional Medicine’s 2018 Annual International Conference. For a full list of coverage, click here.