Biological Mechanisms Involved In Wheat Sensitivity Explained

Researchers at Columbia University Medical Center have found a possible explanation for why some people experience gastrointestinal symptoms after consuming wheat, even in the absence of a wheat allergy or celiac disease. The results of the study – which were published in the journal, Gut – suggest that some wheat-sensitive individuals have a compromised intestinal barrier, which contributes to a systemic inflammatory response.

Celiac disease is an autoimmune disorder in which the immune system mounts an attack against the intestinal lining when genetically-predisposed individuals consume gluten-containing grains. The source of the gluten could be from wheat, barley or rye, and gastrointestinal symptoms of the condition include diarrhea, bloating and abdominal pain.

Interestingly, some individuals experience celiac-like symptoms in response to gluten, despite the lack of blood, tissue and genetic biomarkers characteristic of the disease. These individuals may also display additional extra-intestinal symptoms including mood changes, cognitive difficulties and fatigue after ingesting gluten.

Though researchers have long struggled to find an explanation for this condition, the current study suggests that wheat or gluten consumption may activate an acute systemic immune activation that is not localized to the intestine. While there are no known biomarkers for the disease – which is known as non-celiac gluten or wheat sensitivity (NCWS) – estimates suggest that it affects approximately 3 million people in the US.

The Columbia researchers studied 80 patients with NCWS, and compared them to 40 people with celiac disease and 40 healthy control participants. In the celiac group, the researchers found that blood samples did not indicate the presence of an innate systemic immune activation, despite the intestinal damage associated with the disease. According to the study investigators, this result suggests that the localized immune response in celiac patients is able to block foreign substances – including bacteria and their associated products – from passing through the damaged intestinal lining and triggering a systemic immune reaction.

On the other hand, the NCWS group showed no intestinal cytotoxic T cells characteristic of celiac disease, but they did show a biomarker consistent with intestinal cellular damage and an acute systemic immune activation. This systemic immune activation is likely due to an increase in the amount of microbial material that passes through the intestinal lining and into the circulation.

“A systemic immune activation model would be consistent with the generally rapid onset of the reported symptoms in people with non-celiac wheat sensitivity,” said Armin Alaedini, assistant professor of medicine at Columbia University Medical Center, and the senior author on the study. “The data suggest that, in the future, we may be able to use a combination of biomarkers to identify patients with non-celiac wheat sensitivity, and to monitor their response to treatment.”

Armin and his colleagues also found that when NCWS patients followed a diet free from wheat and other similar cereals for a six month period, they were able to reduce their levels of immune activation back down to normal levels, and limit biomarkers of intestinal cell damage. These patients also reported improvements in both their intestinal and extra-intestinal symptoms after following the wheat-free diet.

According to Armin and his team, they hope to perform future studies aimed at identifying the mechanisms which control the intestinal damage, and eventual failure of the epithelial lining. In addition, they hope to determine whether the identified immune biomarkers may aid in the diagnosis of NCWS.