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Perceived food hypersensitivity is a prevalent, but poorly understood condition. In this review article, we summarize narratively recent literature including results of our 10 years' interdisciplinary research program dealing with such patients. The patients (more than 400) included in our studies were all adults referred to a university hospital because of gastrointestinal complaints self-attributed to food hypersensitivity. Despite extensive examinations, food allergy was seldom diagnosed. The majority of the patients fulfilled the diagnostic criteria for irritable bowel syndrome. In addition, most suffered from several extra-intestinal health complaints and had considerably impaired quality of life. However, psychological factors could explain only approximately 10% of the variance in the patients' symptom severity and 90% of the variance thus remained unexplained. Intolerance to low-digestible carbohydrates was a common problem and abdominal symptoms were replicated by carbohydrate ingestion. A considerable number of patients showed evidence of immune activation by analyses of B-cell activating factor, dendritic cells and "IgE-armed" mast cells. Multiple factors such as immune activation, disturbed intestinal fermentation, enteric dysmotility, post-infectious changes and "local" allergy in the gut as well as psychological disturbances may play a role in the pathophysiology of perceived food hypersensitivity. Hence, our results support the view that management of these patients should be interdisciplinary.

Purpose: Enterometabolic disturbances may cause meal-related symptoms. We performed a functional evaluation of the intestinal microflora in patients with unexplained, self-reported food hypersensitivity by measuring fecal short-chain fatty acids (SCFAs)., Patients and Methods: Thirty-five consecutive patients with self-reported food hypersensitivity and 15 healthy volunteers of similar age, gender, and body mass index collected all feces for 72 hours. Fecal concentrations of acetic, propionic, n-butyric, i-butyric, n-valeric, i-valeric, n-caproic, and i-caproic acids were analyzed by gas-liquid chromatography. Concentrations and excretions (output) of SCFAs in patients and controls were compared and related to gastrointestinal symptoms., Results: Despite nonsignificant differences between patients and controls for both total and individual SCFA concentrations and excretions, n-butyric acid comprised a higher (P = 0.035) and acetic acid a lower (P = 0.012) proportion of total SCFA in patients compared to controls. There were no significant correlations between symptom scores and concentrations or excretions of individual or total SCFAs, but the proportion of n-butyric acid was significantly higher in patients with severe symptoms compared to patients with moderate symptoms (P = 0.016)., Conclusion: The results indicate an enterometabolic disturbance in patients with self-reported food hypersensitivity. Higher proportions of n-butyric acid may be related to abdominal symptom generation, but may also protect against organic bowel disease. Further studies are needed to clarify these aspects.

OBJECTIVE. Intestinal infection with Giardia lamblia may lead to therapy-resistant, long-lasting post-giardiasis irritable bowel syndrome (IBS). We report two open pilot studies aiming to treat this condition, using either antibiotics or bacterio-therapy. MATERIAL AND METHODS. Twenty-eight patients with persistent abdominal symptoms, following clearance of G. lamblia infection, were investigated. Eighteen received treatment with rifaximin plus metronidazole (8-10 days) whereas 10 received a suspension of live faecal flora, installed into the duodenum during gastro-duodenoscopy. Customary abdominal symptoms and symptoms following a lactulose breath test were quantified by questionnaires. Hydrogen and methane production after lactulose were analysed in expired air and excretion of fat and short-chain fatty acids (SCFAs) was examined in faeces. RESULTS. As compared with pre-treatment values, total customary symptom scores were barely significantly reduced (p = 0.07) after antibiotics, but were highly significantly reduced (p = 0.0009) after bacterio-therapy. However, symptom improvement following bacterio-therapy did not persist 1 year later. Hydrogen breath excretion was slightly reduced after antibiotics, but not after bacterio-therapy. Compared with healthy persons, faecal excretion of fat was significantly increased in Giardia-cured patients. SCFAs were increased in the bacterio-therapy group, and were not influenced by therapy. CONCLUSIONS. Both antibiotics and bacterio-therapy were ineffective with respect to cure of post-giardiasis IBS. High faecal excretion of fat and SCFAs suggests that intestinal malabsorption of fat and carbohydrates may play a role in the IBS-like complaints of these patients.

Objective: Malabsorption of low-digestible carbohydrates is physiological, but poorly tolerated in some patients. We investigated symptom anticipation and microbial fermentation as possible mechanisms of carbohydrate intolerance in patients with self-reported food hypersensitivity., Material and Methods: In a randomized, double-blind, cross-over study, 27 consecutive patients with unexplained, self-reported food hypersensitivity were given 10 g lactulose and 10 g glucose (placebo). Symptoms and pulmonary excretion of hydrogen and methane were assessed. Short-chain fatty acids (SCFAs), lactate and prostaglandin E(2) (PGE(2)) were analyzed in rectal dialysis fluid, and compared to dialysates from nine healthy volunteers., Results: Post-lactulose symptom scores were correlated with habitual symptom scores (r = 0.6, p = 0.001), significantly higher than post-glucose symptom scores (p = 0.01) and significantly higher in patients than controls (p = 0.0007). Levels of SCFAs, lactate and PGE(2) in rectal dialysates were not significantly different after lactulose and glucose, or between patients and controls. Hydrogen excretion was not correlated with symptom scores., Conclusions: The findings suggest that self-reported food hypersensitivity is related to microbial fermentation of malabsorbed carbohydrates and not to symptom anticipation solely. Levels of SCFAs, lactate and PGE(2) in rectal dialysates could not explain the fermentation-associated hypersensitivity.

Objective: Carbohydrate malabsorption causes more symptoms in patients with functional gastrointestinal disorders than in healthy individuals. The purpose of this study was to investigate whether this could be explained by differences in ileal brake hormone secretion., Material and Methods: Eighteen consecutive patients with functional abdominal complaints, referred to our clinic for investigation of self-reported food hypersensitivity, were included in the study and compared with 15 healthy volunteers. All subjects ingested a mixture of 25 g fructose and 5 g sorbitol. Pulmonary hydrogen and methane excretion and plasma glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) levels were measured during the next 3 h. Both habitual and post-test symptoms were assessed., Results: Malabsorption of fructose and sorbitol was present in 61% of the patients and 73% of the controls. Nevertheless, the patients experienced significantly more symptoms following carbohydrate challenge, and 78% of the patients claimed that the challenge replicated their habitual gastrointestinal complaints. No significant differences in gas excretion or GLP-1 and PYY levels were found between patients and controls or between symptomatic and asymptomatic carbohydrate malabsorbers. A weak correlation between hydrogen excretion and PYY levels was demonstrated in non-producers of methane., Conclusions: Neither intestinal gas production nor ileal brake hormone secretion seems to play a role in the symptomatology of carbohydrate intolerance in patients with self-reported food hypersensitivity. Other mechanisms related to bacterial fermentation may be involved and should be investigated further.

Objectives: After a large waterborne outbreak of Giardia infection in Bergen, some patients experienced persisting abdominal symptoms despite metronidazole treatment. This study aimed at investigating possible causes for their symptoms., Methods: Over a 15 month period, 124 referred patients were evaluated in a prospective cohort analysis with a standardised investigation including duodenal biopsies and aspirate, blood tests and faecal parasite and calprotectin tests. Recovered subjects were recruited for symptom analysis., Results: Persisting Giardia duodenalis infection was found in 40 patients (32.3%). Duodenal biopsies showed signs of inflammation in 57 patients (47.1%). Microscopic duodenal inflammation was present in 34 (87.2%) of the Giardia positive and 23 (28.0%) of the Giardia negative patients. There were significant associations between persistent Giardia positivity, microscopic duodenal inflammation and a positive calprotectin test. Duodenal aspirate and duodenal biopsies performed poorly in diagnosis of persistent giardiasis., Conclusions: In patients with persisting symptoms after metronidazole treated Giardia infection we commonly found chronic Giardia infection and microscopic duodenal inflammation, especially in illness duration less than 7 months. Both these findings subsided over time. Increasingly, investigations could not determine a definite cause for the persistent symptoms. The very long-term post-giardiasis diarrhoea, bloating, nausea and abdominal pain documented here need further study.

Observation: Intestinal gas production and abdominal discomfort can be triggered by the ingestion of carbohydrates such as lactulose. Using plain abdominal radiographs, we studied whether subjective complaints after a lactulose breath test would be quantitatively related to intestinal gas volumes., Methods: Abdominal symptoms after the breath test were quantified by a written questionnaire and gas volumes were scored in plain abdominal radiographs, in 50 consecutive patients with unexplained, irritable bowel syndrome-like symptoms. Breath excretion of hydrogen and methane was determined in all patients., Results: Forty-two (84%) of the patients claimed that their post-breath test symptoms were a true replicate of their customary discomfort. Total symptom scores (sum of scores for pain/discomfort, borborygmi, bloating, diarrhea, constipation) or any specific symptom score were not significantly correlated to gas volume scores (r=-0.04; P=0.8 for total symptom score). The 13 (26%) methane producers had significantly higher mean gas volume scores compared with nonproducers (0.38 vs. 0.24; P=0.0008), but fewer symptoms (total symptom score 11.9 vs. 18.2; P=0.17)., Conclusion: Intestinal gas volume, as scored in plain abdominal radiographs, is not correlated with abdominal discomfort after lactulose challenge. Intestinal gas may not be the major cause of abdominal discomfort following carbohydrate ingestion in patients with functional gut disorders.