A lot of the research on gluten is done in the context of celiac disease (CD), a genetic autoimmune disease characterized by intestinal damage and an increased immune response as a result of gliadin consumption, a component of gluten. People with CD should avoid gluten to avoid this damage. Untreated CD combined with continued gluten intake is associated with a greater risk of death. People without CD or people with CD that also avoid gluten do not experience this increased risk.

Non-Celiac Gluten Sensitivity (NCGS) is another big topic for gluten researchers. There is some evidence to suggest people with non-celiac intestinal disorders like Irritable Bowel Syndrome (IBS) are more likely to experience flatulence, pain, and nausea after consuming gluten than people with healthy intestinal tracts. However, people with NCGS do not experience the same level of damage after eating gluten than people with CD. So, the discomfort of people with NCGS may be better explained by other carbohydrates associated with gluten, rather than autoimmune damage. Researchers examining self-diagnosis of gluten sensitivity suggest that many people with NCGS do not actually display any sensitivity and the symptoms may be the result of discussions related to gluten causing intestinal problems, also known as a 'nocebo' effect.

People with CD should avoid gluten at all costs, while people with other intestinal disorders may experience mild to severe discomfort after gluten consumption, possibly due to wheat's ability to produce gas. There is currently no evidence that gluten causes tissue damage when consumed by people without CD.