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Non-Celiac Gluten Sensitivity Research

New Research Explains How Gluten Sensitivity Differs From Celiac Disease

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Updated January 25, 2013

Written or reviewed by a board-certified physician. See About.com's Medical Review Board.

Non-Celiac Gluten Sensitivity Research
© Getty Images/Ryan McVay

Research into non-celiac gluten sensitivity — also known as gluten intolerance — increasingly is proving that you can get serious symptoms from gluten ingestion without having celiac disease.

In a landmark study on gluten sensitivity released in early 2011, prominent celiac researcher Dr. Alessio Fasano concluded that "gluten sensitivity" represents a completely different condition from celiac disease, and most of the people who suffer from gluten sensitivity will never develop celiac. While his research is certainly of interest to the medical community, it's important to note that his research has not yet been replicated and so the medical community at large still considers this a theory in development.

Dr. Fasano and a group made up of prominent celiac disease researchers, including Drs. Peter Green (head of the Columbia University Celiac Disease Center) and Dr Marios Hadjivassiliou (a consultant neurologist and expert in gluten ataxia), followed up the initial study with a consensus statement released in February 2012 proposing ways to differentiate between celiac disease, gluten sensitivity and gluten ataxia.

Additional researchers also have chimed in with findings. Some studies show that some gluten-sensitive people have similar metabolic profiles to diagnosed celiacs, indicating that there might be a pre-celiac condition. Other studies back Dr. Fasano's findings that gluten can trigger symptoms in people who don't have classic celiac disease.

Research into gluten sensitivity is evolving rapidly. In addition, more and more frequently, people who have positive celiac disease blood tests but a negative biopsy are being handed diagnoses of gluten sensitivity.

In some cases, their physician says they can eat gluten in moderation, or they are told to follow the gluten-free diet but that they don't need to be as careful as celiac patients. Others are told they're "potential" celiac disease patients, and to check back in a year or so for more testing to see if they've developed the condition.

More research will be needed to determine if people with gluten sensitivity really can ingest small amounts of gluten without damage, or if a specific sub-group of gluten-sensitives will eventually go on to develop celiac disease.

Read more on possible health risks in gluten sensitivity: Gluten Sensitivity Health Risks

U. of Maryland Pegs 'Gluten Sensitivity' As Real Condition

In Dr. Fasano's initial gluten sensitivity research, published online in March 2011 in BMC Medicine, the researchers found distinctive differences between celiac disease and gluten sensitivity on the molecular level, even though symptoms of the two conditions overlapped considerably.

Dr. Fasano and other University of Maryland researchers compared 42 diagnosed celiacs who had Marsh 3 or Marsh 4 intestinal damage with 26 people whose intestines showed little or no damage, but who still clearly reacted to gluten.

For each participant, the researchers determined the level of intestinal permeability (in celiac disease, your intestines become more permeable, which can allow proteins to escape into the blood stream). They also looked at genetics, along with the expression of genes in the small intestines.

The study found differences in intestinal permeability between the groups of people, along with differences in the expression of the genes that regulate the immune response. That indicates gluten sensitivity is a different condition than celiac disease, according to Dr. Fasano.

Differences in Celiac, Gluten Sensitivity Stem From Immune System Responses

The differences between the two conditions stem from differing immune system responses, Dr. Fasano says.

In gluten sensitivity, the innate immune system -- an older part of the immune system and the body's first line of defense against invaders -- responds to gluten ingestion by fighting the gluten directly. That creates inflammation both inside and outside the digestive system, according to Dr. Fasano.

Meanwhile, celiac disease involves both the innate immune system and the adaptive immune system, he says. The adaptive immune system is a more advanced, sophisticated part of the immune system, and miscommunications between adaptive immune system cells lead those cells to fight your body's own tissues, creating the villous atrophy seen in celiac disease.

People with gluten sensitivity do not get villous atrophy, even though they can still experience near-identical symptoms to celiac, including diarrhea, bloating, abdominal pain, joint pain, depression, brain fog and migraines, according to Dr. Fasano. (Read more on potential symptoms here: Gluten Sensitivity Symptoms.)

However, only those people with the adaptive immune system response unique to celiac disease are at risk for developing intestinal lymphoma and other conditions associated with celiac, such as osteoporosis, Dr. Fasano says.

Some of the gluten-sensitive people included in Dr. Fasano's study had minor intestinal damage (classified as Marsh 1 or 2), but that damage had different biomarkers than those seen in celiac disease.

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