Impact of Acute and Sub-Acute Gluten Exposure on Gastrointestinal Symptoms and Psychological Responses in Non-Coeliac Gluten Sensitivity: A Randomised Crossover Study.

BACKGROUND/AIMS: Non-coeliac gluten sensitivity (NCGS) is a controversial entity, characterised by symptom improvement with gluten exclusion in the absence of coeliac disease. We primarily investigated the effects of acute and sub-acute gluten on psychological and mood profiles, with secondary outcomes examining gastrointestinal symptoms and biological markers in healthy controls (HC) and individuals with NCGS.

METHODS

A randomised, single-blind, crossover study used acute (16 g gluten or whey in yoghurt) and sub-acute (gluten-containing (16 g) or gluten-free muffins per day for 5 days) challenges. (Extra)intestinal symptoms, intestinal permeability, high-sensitive C-reactive protein and cortisol awakening response were assessed. Responses over time were analysed using generalised linear mixed models.

RESULTS

Twenty HCs (15% men, mean age 30 years) and 16 individuals with NCGS (31% men, mean age 33 years) participated. No significant group-by-nutrient interactions were observed. Negative affect scores were higher and positive affect scores were lower in NCGS compared to HC (p = 0.01 and p = 0.04, respectively). Participants experienced higher tension scores after gluten compared with placebo (p = 0.01 acute; p = 0.05 sub-acute) regardless of the group. After acute administration, fatigue scores increased in NCGS (p = 0.03) compared with HC regardless of nutrient intake. After sub-acute administration, abdominal pain scores (p < 0.001) and bloating (p = 0.001) increased in NCGS compared with HC regardless of nutrient intake. No differences were found for biological markers.

CONCLUSIONS

These findings reveal that NCGS is characterised by baseline differences in affect, and higher acute fatigue and subacute gastrointestinal symptoms that are not gluten-specific. This may be explained by nocebo effects, warranting research into novel mechanisms and re-evaluating the NCGS definition.

TRIAL REGISTRATION: ClinicalTrials.gov no: NCT03798262; NCT03798249.