Reasons for Wheat Sensitivity

Recent study finds that a compromised intestinal barrier and systemic immune activation may explain symptoms in non-celiac patients.

A recent study conducted by researchers at Columbia University Medical Center (CUMC) may have identified a biological reason why people who do not have celiac disease nevertheless experience various symptoms in response to wheat ingestion. The findings, published in the journal Gut, indicate that these people may have a weakened intestinal barrier, which results in an inflammatory immune response throughout the body.Wheat Sensitivity

Non-celiac Gluten or Wheat Sensitivity

Celiac disease is a genetic autoimmune disorder in which the immune system attacks the lining of the small intestine after the ingestion of gluten from wheat, rye, barley or related cereals. This can result in various gastrointestinal (GI) symptoms, such as abdominal pain, diarrhea and bloating.1

However, some people experience celiac-like GI symptoms, as well as various extra-intestinal symptoms-like fatigue, cognitive difficulties or mood disturbances-after ingesting foods that contain gluten, even though they lack the distinguishing blood, tissue or genetic markers of celiac disease. This condition, called non-celiac gluten or wheat sensitivity (NCWS), is currently estimated to affect around 1% of the population (about 3 million Americans)-about the same prevalence as celiac disease.

Prior to this study, the reason for NCWS remained a mystery to researchers. “What motivated me to study this condition was that, despite the large number of people affected and the tremendous interest from the medical community to help these individuals, the causes and mechanism of the associated symptoms have remained unknown and no biomarkers have been available to aid in the diagnosis of patients,” lead study author Armin Alaedini, PhD, told ADVANCE. Alaedini, an assistant professor of medicine at Columbia, also holds an appointment in Columbia’s Institute of Human Nutrition and is a member of the Celiac Disease Center.

Acute Systemic Immune Activation

For this study, CUMC researchers analyzed 80 individuals with NCWS, 40 celiac disease patients and 40 healthy controls. Although extensive intestinal damage is a hallmark of celiac disease, blood markers of innate systemic immune activation were not elevated in the celiac disease group. This may mean that the intestinal immune response in celiac patients has the ability to neutralize microbes or microbial components that may pass through the damaged intestinal cellular barrier, thus preventing a systemic inflammatory response against highly immunostimulatory molecules.1

Researchers found a significant difference in the NCWS group. Though they lacked the intestinal cytotoxic T cells seen in celiac patients, they did have a marker of intestinal cellular damage that corresponded to serologic markers of acute systemic immune activation. These results might mean that the identified systemic immune activation in NCWS is related to increased translocation of microbial and dietary components from the gut into circulation, partly due to intestinal cell damage and weakening of the intestinal barrier.1

Additionally, researchers observed that NCWS patients were able to normalize their levels of immune activation and intestinal cell damage markers if they followed a gluten-free diet for six months. These patients reported that the changes were accompanied by significant improvements in both intestinal and non-intestinal symptoms.

Significance of Study Findings

“Our study shows that the symptoms reported by individuals with this condition are not imagined, as some people have suggested,” said study co-author Peter H. Green, MD, the Phyllis and Ivan Seidenberg Professor of Medicine at CUMC and director of the Celiac Disease Center, in a July 26 CUMC press release. “It demonstrates that there is a biological basis for these symptoms in a significant number of these patients.”1
“These results shift the paradigm in our recognition and understanding of non-celiac wheat sensitivity and will likely have important implications for diagnosis and treatment,” stated co-author Umberto Volta, MD, professor of internal medicine at the University of Bologna, in the press release. CUMC researchers collaborated with the University of Bologna in Italy for this study.1

Currently, according to Alaedini, the only way to diagnose NCWS is through thorough clinical examinations that involve food restriction and food challenges. “As our work shows that there are clear biological changes in the affected patients, which are associated with certain biomarkers, a blood test may become available in the future for diagnosing patients,” he said. “As we learn more about the potential mechanisms involved in non-celiac wheat sensitivity, we will also hopefully be able to identify and evaluate effective new treatment strategies.”

What’s Next?

According to Alaedini, the research team is planning a number of further studies. Though the team identified systemic immune activation and intestinal cell damage in people with NCWS, they have yet to determine how wheat-containing food might be causing the intestinal cell damage. “In other words, the mechanism and trigger for the presumed intestinal damage in the affected individuals are not known,” explained Alaedini. “We are now working on this.”

In addition, because doctors don’t have any blood tests currently available to help diagnose people with NCWS and to assess their response to treatment, the team is developing a blood test to accurately diagnose cases of NCWS. “Considering the number of people believed to be affected by this condition and the significant impact on patients’ health, these are important areas to investigate and deserve more attention and research funding,” Alaedini said.


1. Columbia University Medical Center. Columbia Researchers Find Biological Explanation for Wheat Sensitivity.

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