Unexplained, self-reported food hypersensitivity. Explorative studies on mechanisms of abdominal symptom generation

Background: Self-reported food hypersensitivity remains unexplained in most cases. Abdominal symptoms, typically consistent with the irritable bowel syndrome (IBS), are common in patients with such unexplained, self-reported food hypersensitivity. The etiology is obscure. Aim: The overall objective of the present study was to investigate possible mechanisms of postprandial abdominal symptom generation. A main purpose was to explore whether and how ingestion of low-digestible carbohydrates act as abdominal symptom triggers in patients with unexplained, self-reported food hypersensitivity. Main results: The findings can be summarized as follows: In study I, fructose-sorbitol malabsorption evoked more symptoms in patients with unexplained, self-reported food hypersensitivity than in healthy controls. Alterations in intestinal gas production and secretion of so-called ileal brake hormones (glucagon-like peptide 1 (GLP-1) and peptide YY (PYY)) could not be demonstrated. In study II, serum levels of chromogranin A (CgA) were found to be lower in patients with unexplained, self-reported food hypersensitivity than in healthy controls. In study III, lactulose malabsorption evoked more symptoms in patients with unexplained, self-reported food hypersensitivity than in healthy controls. The symptoms could not be fully explained by symptom anticipation, because lactulose induced more symptoms than placebo (glucose). Associated alterations in intestinal gas production and rectal levels of prostaglandin E2 (PGE2) and microbial fermentation products could not be demonstrated. In study IV, mechanisms of diarrhoea in a mouse model of food allergy were investigated. Changes within the jejunum were demonstrated in the food allergic mice, with development of muscular hypocontractility, increased levels of cytokines IL-4 and IL-6 and high numbers of mast cells. In study V, fecal levels of short-chain fatty acids (SCFA) were investigated, and the profile was different between patients with unexplained, self-reported food hypersensitivity and healthy controls. Increased proportions of butyric acid were demonstrated in the patient group, particularly in individuals with severe symptoms. Conclusion: Taken together, the results suggest that intolerance to low-digestible carbohydrates plays an important role in abdominal symptom generation in patients with unexplained, self-reported food hypersensitivity. Disturbances of intestinal motility may contribute to gastrointestinal symptom development by increasing the amount of malabsorbed carbohydrates. Altered intestinal fermentation is a potential cause of the patients’ unexplained symptoms