Gluten Sensitivity: A Gut-Brain Communication Disorder, Not a Gluten Disorder

Recent research shows that so-called gluten sensitivity is often not caused by gluten itself, but by a complex interaction between the gut and the brain. Factors such as fermentable carbohydrates (FODMAPs), anxiety, and expectations can trigger real symptoms, leading millions of people to avoid gluten unnecessarily. The condition, now seen as part of gut-brain communication disorders, requires a personalized approach that unites nutrition and mental health.

Non-celiac gluten sensitivity is a condition in which people report symptoms such as abdominal pain, bloating, fatigue, and discomfort after eating foods containing wheat, rye, or barley, even without having celiac disease or a wheat allergy.

It is estimated that up to 10% of the world's population claims to suffer from this sensitivity. However, recent studies show that, in most cases, gluten may not be the real culprit.

Recent research, reviewed by scientists at the University of Melbourne and published in The Lancet, indicates that, for a large portion of people, the symptoms attributed to gluten are caused by other factors, mainly fermentable carbohydrates, known as FODMAPs, or by psychological and neurological mechanisms involving communication between the gut and the brain.

These carbohydrates are found naturally in various foods, including wheat, onions, legumes, and fruits, and can cause gas and discomfort in sensitive individuals.

The most striking finding is that so-called "gluten sensitivity" may be linked to how the brain interprets signals from the gut. When a person believes that a certain food will cause discomfort, the brain may amplify intestinal sensations, a phenomenon known as the nocebo effect, the opposite of the placebo effect.

This connection is so strong that many patients who report reacting to gluten exhibit similar responses when consuming wheat, placebos, or other gluten-free foods, especially in people with irritable bowel syndrome.

In other words, non-celiac gluten sensitivity may be part of a broader spectrum of gut-brain interaction disorders, and not a specific reaction to gluten. This represents an important shift in how medicine understands and treats this condition.

Currently, there are no laboratory tests or biomarkers that confirm the presence of non-celiac gluten sensitivity. The diagnosis is made by exclusion, that is, only after ruling out celiac disease, food allergies, and other gastrointestinal conditions.

Studies also face methodological difficulties; in many tests, the food used to "provoke" symptoms contains not only gluten but also FODMAPs, making it difficult to know which component actually triggers the discomfort.

The ideal treatment should balance dietary adaptation with psychological support and attention to balanced nutrition. Completely avoiding gluten may be unnecessary and, in some cases, even harmful, as gluten-free products are often more expensive, less nutritious, and influenced by trends and marketing campaigns.

According to researchers, the best approach is a personalized one, carried out by doctors and nutritionists who consider both biological and emotional factors.

Associate Professor Jessica Biesiekierski, one of the leading researchers in the field, argues that it's time to change the popular narrative about gluten. “We need to abandon the idea that gluten is inherently harmful. Many people are avoiding gluten unnecessarily, when the problem may lie in other food components or in how the body reacts to them,” she explains.

Gastroenterologist Jason Tye-Din emphasizes that correctly distinguishing non-celiac gluten sensitivity from other intestinal diseases is essential to ensure accurate diagnoses and more effective treatments.

Non-celiac gluten sensitivity is a real, but complex condition. Science shows that the discomfort suffered by those who experience it should not be ignored; however, gluten may not be the true culprit.

The interaction between the gut, the brain, and emotional factors seems to play a much more important role than previously thought. Understanding this balance is the first step towards more humane treatments, based on science and not on fear of food.

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Non-coeliac gluten sensitivity

JessicaR Biesiekierski, Daisy Jonkers, Carolina Ciacci, and Imran Aziz

The Lancet, October 22, 2025

DOI: 10.1016/S0140-6736(25)01533-8

Abstract:

Non-coeliac gluten sensitivity (NCGS) refers to individuals who report intestinal and extraintestinal symptoms related to the ingestion of gluten-based or wheat-based foods, in the absence of coeliac disease or wheat allergy. Gluten is found in multiple cereals, including wheat, rye, and barley, although the precise trigger of symptoms in NCGS remains unclear. Although approximately 10% of adults worldwide self-report gluten or wheat sensitivity, meta-analyses suggest that, during controlled challenge studies, 16–30% of these individuals have symptoms specifically triggered by gluten. However, methodological variability, including the presence of fermentable carbohydrates in challenge preparations, limits interpretation. Current evidence suggests that fermentable carbohydrates and nocebo effects contribute considerably to symptom generation in many cases. The substantial size of the gluten-free market raises questions about commercial and media influences on how NCGS is portrayed, and on the direction of related research. Definitive diagnosis of NCGS remains elusive due to the absence of biomarkers, significant overlap with disorders of gut–brain interaction, and methodological challenges in dietary evaluation. Until causative agents are identified and diagnostic tests developed, NCGS remains a diagnosis of exclusion, requiring careful systematic evaluation. Management approaches should balance dietary modification with recognition of psychological factors while ensuring nutritional adequacy. This Review critically examines current evidence regarding NCGS as a distinct entity, explores potential mechanisms, and provides practical guidance for assessment and management, while acknowledging major uncertainties in the field.