This study evaluates why people with celiac disease and non-celiac gluten/wheat sensitivity develop rapid onset symptoms within hours of gluten exposure. Half of subjects will be given gluten and half will not.

When a person with celiac disease is exposed to gluten, their immune system attacks their bowel and causes abdominal pain, bloating, and diarrhea. This process takes 24-72 hours to occur. Some people without celiac disease develop similar symptoms when they eat gluten or wheat. Doctors and scientists do not know what causes this sensitivity to gluten. People with celiac disease and non-celiac gluten sensitivity report symptoms within hours of being exposed to gluten. This study evaluates why this occurs by looking at changes in blood, urine, stool, and the bowel after being given gluten.

Inclusion Criteria for subjects with Celiac Disease:

• Biopsy proven celiac disease diagnosed at least 2 years prior to recruitment
• Attest to following a gluten free diet to the best of their ability
• Quiescent symptoms on a gluten free diet
• Negative tissue transglutaminase at time of recruitment (to be collected with baseline blood work)
• A prior endoscopy with small bowel biopsies reviewed by a gastrointestinal pathologist revealing healing

Inclusion Criteria for subjects with Non-Celiac Gluten Sensitivity:

• Meet diagnostic consensus criteria as defined by Ludvigsson et al in "The Oslo definitions for coeliac disease and related terms"
• Attest to following a gluten free diet to the best of their ability
• Quiescent symptoms on a gluten free diet
• Prior negative evaluation for celiac disease (including tissue transglutaminase IgA with total IgA or small bowel biopsies)
• If subjects have had a small bowel biopsies revealing increased intraepithelial lymphocytes (IELs), they will be reviewed as a separate subgroup

Inclusion Criteria for Normal Subjects:

• No gastrointestinal diagnosis (reflux, eosinophilic esophagitis, inflammatory bowel disease, or irritable bowel syndrome)
• No gastrointestinal symptoms (diarrhea, abdominal pain, nausea, vomiting, weight loss)
• No family history of celiac disease
• Will not be required to have a baseline biopsy

Exclusion Criteria:

• Tobacco use
• Symptomatic coronary disease
• Active, severe pulmonary disease
• Baseline oxygen requirement
• Coagulopathy (INR>1.5)
• Mastocytosis
• Active H. pylori infection
• Treated celiac disease with neutrophilia or eosinophilia secondary to infection
• Diabetes (type 1 and type 2)
• Crohn's disease or Ulcerative colitis
• Microscopic colitis
• Dermatitis herpetiformis
• Gastroparesis
• Pregnant women

Subjects exposed to the following medications during their respective time frames will be excluded:

• NSAIDs (24 hours)
• Leukotriene inhibitors (24 hours)
• Mast cell stabilizers (24 hours)
• Benzodiazepines (24 hours)
• H2 blockers (2 days)
• H1 blockers (7 days)
• Steroids (systemic or topically active within gastrointestinal tract) (30 days)
• Topical steroids (14 days)
• Intermittent (up to once weekly) tranquilizer (trazodone, doxepin) use (7 days)
• Chronic tricyclic antidepressant or tranquilizer use (trazodone, doxepin) Use of these medications will also be prohibited during the study duration (AAAAI and AAOA).

Subjects will be block randomized to either gluten-containing or placebo challenge.