Gluten
It was hypothesized that gluten, as occurs in celiac disease, is the cause of NCGS. In addition to its ability to elicit abnormal responses of the immune system, in vitro studies on cell cultures showed that gluten is cytotoxic and causes direct intestinal damage. Gluten and gliadin promote cell apoptosis (a form of programmed cell death) and reduce the synthesis of nucleic acids (DNA and RNA) and proteins, leading to a reduction in the viability of cells. Gluten alters cellular morphology and motility, cytoskeleton organization, oxidative balance and intercellular contact (tight junction proteins). Other proteins
Some people may have a reaction to other proteins (α-amylase/trypsin inhibitors [ATIs]) present in gluten-containing cereals that are able to inhibit amylase and trypsin. They have been identified as the possible activator of the innate immune system in celiac disease and NCGS.ATIs are part of the plants natural defence against insects and may  cause toll-like receptor 4 (TLR4)-mediated intestinal inflammation in humans. These TLR4-stimulating activities of ATIs are limited to gluten-containing cereals (wheat, rye, barley, and derivatives) and may induce innate immunity in people with celiac disease or NCGS. ATIs resist proteolytic digestion. ATIs are about 2%–4% of the total protein in modern wheat and are present in commercial gluten. A 2017 study in mice demonstrated that ATIs exacerbate preexisting inflammation and may also worsen it at extraintestinal sites.
Gastrointestinal
Gastrointestinal symptoms may include any of the following: abdominal pain, bloating, bowel habit abnormalities (either diarrhea or constipation), nausea, aerophagia, flatulence, gastroesophageal reflux disease, and aphthous stomatitis. Extraintestinal
NCGS can cause a wide range of extraintestinal symptoms, which can be the only manifestation of NCGS in absence of gastrointestinal symptoms. These include any of the following: headache, migraine, "foggy mind", fatigue, fibromyalgia, joint and muscle pain, leg or arm numbness, tingling of the extremities, dermatitis (eczema or skin rash), atopic disorders such as asthma, rhinitis, other allergies, depression, anxiety, iron-deficiency anemia, folate deficiency, or autoimmune diseases. NCGS is also linked to a wide spectrum of neurological and psychiatric disorders, including  ataxia, schizophrenia, epilepsy, peripheral neuropathy, encephalopathy, vascular dementia, eating disorders, autism, attention deficit hyperactivity disorder (ADHD), hallucinations (so-called "gluten psychosis"),  and various movement disorders (restless legs syndrome, chorea, parkinsonism, Tourette syndrome, palatal tremor,  myoclonus, dystonia, opsoclonus myoclonus syndrome, paroxysms, dyskinesia, myorhythmia, myokymia).Above 20% of people with NCGS have IgE-mediated allergy to one or more inhalants, foods, or metals, among which most common are mites, graminaceae, parietaria, cat or dog hair, shellfish, and nickel. Approximately 35% of patients suffer other food intolerances, mainly lactose intolerance. Causes
The pathogenesis of NCGS is not yet well understood, but the activation of the innate immune system, the direct cytotoxic effects of gluten, and probably the cytotoxicity of other wheat molecules are implicated. Besides gluten, other components in wheat, rye, barley, and their derivatives, including amylasetrypsin inhibitors (ATIs) and FODMAPs, may  cause symptoms.