Fructose malabsorption in ChREBP-deficient mice disrupts the small intestine immune microenvironment and leads to diarrhea-dominant bowel habit changes.

BACKGROUND: The mechanism by which incompletely absorbed fructose causes gastrointestinal symptoms is not fully understood. In this study, we investigated the immunological mechanisms of bowel habit changes associated with fructose malabsorption by examining Chrebp-knockout mice exhibiting defective fructose absorption. METHODS: Mice were fed a high-fructose diet (HFrD), and stool parameters were monitored. The gene expression in the small intestine was analyzed by RNA sequencing. Intestinal immune responses were assessed. The microbiota composition was determined by 16S rRNA profiling. Antibiotics were used to assess the relevance of microbes for HFrD-induced bowel habit changes. RESULTS: Chrebp-knockout (KO) mice fed HFrD showed diarrhea. Small-intestine samples from HFrD-fed Chrebp-KO mice revealed differentially expressed genes involved in the immune pathways, including IgA production. The number of IgA-producing cells in the small intestine decreased in HFrD-fed Chrebp-KO mice. These mice showed signs of increased intestinal permeability. Chrebp-KO mice fed a control diet showed intestinal bacterial imbalance, which the HFrD exaggerated. Bacterial reduction improved diarrhea-associated stool parameters and restored the decreased IgA synthesis induced in HFrD-fed Chrebp-KO mice. CONCLUSIONS: The collective data indicate that gut microbiome imbalance and disrupting homeostatic intestinal immune responses account for the development of gastrointestinal symptoms induced by fructose malabsorption.

Fructose malabsorption: causes, diagnosis and treatment.

This review intends to act as an overview of fructose malabsorption (FM) and its role in the aetiology of diseases including, but not limited to, irritable bowel syndrome (IBS) and infantile colic and the relationship between fructose absorption and the propagation of some cancers. IBS results in a variety of symptoms including stomach pains, cramps and bloating. Patients can be categorised into two groups, depending on whether the patients' experiences either constipation (IBS-C) or diarrhoea (IBS-D). FM has been proposed as a potential cause of IBS-D and other diseases, such as infantile colic. However, our knowledge of FM is limited by our understanding of the biochemistry related to the absorption of fructose in the small intestine and FM's relationship with small intestinal bacterial overgrowth. It is important to consider the dietary effects on FM and most importantly, the quantity of excess free fructose consumed. The diagnosis of FM is difficult and often requires indirect means that may result in false positives. Current treatments of FM include dietary intervention, such as low fermentable oligo-, di-, monosaccharides and polyols diets and enzymatic treatments, such as the use of xylose isomerase. More research is needed to accurately diagnose and effectively treat FM. This review is designed with the goal of providing a detailed outline of the issues regarding the causes, diagnosis and treatment of FM.

Gene variants of the SLC2A5 gene encoding GLUT5, the major fructose transporter, do not contribute to clinical presentation of acquired fructose malabsorption.

BACKGROUND: While role of ALDOB-related gene variants for hereditary fructose intolerance is well established, contribution of gene variants for acquired fructose malabsorption (e.g. SLC2A5, GLUT5) is not well understood. METHODS: Patients referred to fructose breath test were further selected to identify those having acquired fructose malabsorption. Molecular analysis of genomic DNA included (I) exclusion of 3 main ALDOB gene variants causing hereditary fructose intolerance and (II) sequencing analysis of SLC2A5 gene comprising complete coding region, at least 20 bp of adjacent intronic regions and 700 bp of proximal promoter. RESULTS: Among 494 patients, 35 individuals with acquired fructose malabsorption were identified based on pathological fructose-breath test and normal lactose-breath test. Thirty four of them (97%) had negative tissue anti-transglutaminase and/or deamidated gliadin antibodies in their medical records. Molecular analysis of SLC2A5 gene of all 35 subjects identified 5 frequent and 5 singular gene variants mostly in noncoding regions (promoter and intron). Allele frequencies of gene variants were similar to those reported in public databases strongly implying that none of them was associated with acquired fructose malabsorption. CONCLUSIONS: Gene variants of coding exons, adjacent intronic regions and proximal promoter region of SLC2A5 gene are unlikely to contribute to genetic predisposition of acquired fructose malabsorption.

A Prospective Multicenter Study on the Prevalence of Fructose Malabsorption in Patients with Chronic Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Patients with chronic inflammatory bowel disease (IBD) might have a higher prevalence of fructose malabsorption than healthy controls. This study's aim was to determine the prevalence and symptom severity of fructose malabsorption in patients with active and inactive IBD. METHODS: The present study was a multicenter noninterventional diagnostic pilot trial. Two hundred fifty-one participants were recruited from 12 outpatient clinics for internal medicine across Germany and from the University of Kiel. Fructose malabsorption was diagnosed by hydrogen breath testing. Patients diagnosed with bacterial overgrowth, non-H2 producers, and patients who were tested positive for lactose malabsorption were excluded. Gastrointestinal symptoms during breath testing were evaluated using four-point subjective items to determine severity of bloating, abdominal pain, and diarrhea. RESULTS: Two hundred five patients (45 with active IBD, 80 with IBD in remission, and 81 healthy controls) were analyzed. The number of patients diagnosed with fructose malabsorption - 35/44 (79.6%) in patients with active IBD, 59/80 (73.8%) inactive IBD, and 66/81 (81.5%) in healthy controls - did not differ between the groups (χ2 [2, N = 205] = 1.48, p = 0.48). However, abdominal pain was more frequent in patients with active IBD than patients with IBD in remission (z = -2.936, p = 0.010), and diarrhea was more frequent in patients with active IBD than in healthy controls (z = 2.489, p = 0.038). CONCLUSIONS: Fructose malabsorption is not more common among patients with IBD than healthy subjects. However, the greater prevalence of patient-reported symptoms among patients with IBD may be of pathological and therapeutic relevance.

Fructose and irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a chronic disorder characterised by recurrent abdominal pain or discomfort and transit disturbances with heterogeneous pathophysiological mechanisms. The link between food and gastrointestinal (GI) symptoms is often reported by patients with IBS and the role of fructose has recently been highlighted. Fructose malabsorption can easily be assessed by hydrogen and/or methane breath test in response to 25 g fructose; and its prevalence is about 22 % in patients with IBS. The mechanism of fructose-related symptoms is incompletely understood. Osmotic load, fermentation and visceral hypersensitivity are likely to participate in GI symptoms in the IBS population and may be triggered or worsened by fructose. A low-fructose diet could be integrated in the overall treatment strategy, but its role and implication in the improvement of IBS symptoms should be evaluated. In the present review, we discuss fructose malabsorption in adult patients with IBS and the interest of a low-fructose diet in order to underline the important role of fructose in IBS.

The Predictive Value of the Hydrogen Breath Test in the Diagnosis of Fructose Malabsorption.

BACKGROUND: Fructose malabsorption is commonly diagnosed by the hydrogen fructose (H2) breath test. However, the mechanisms behind fructose malabsorption in humans are not well understood and the clinical relevance of this test is considered controversial. Hence, the main aim of this study is to evaluate the predictive value of the H2 breath test. METHODS: Regarding exclusion criteria, the study enrolled 562 consecutive patients, enlisted to a gastroenterology clinic between 2009 and 2011 for testing malabsorption. In the final data analysis, 246 patients were included. Ecotrophologists used 3 categories to rate dietary success: complete response, partial response and no response to the diet. They also rated the occurrence of abdominal pain, diarrhoea and bloating during the H2 breath test. Ordinal regression analysis using SPSS was performed to evaluate whether H2 breath test results - measured as the maximum H2 level, the maximum increase in H2, and the area under the curve (AUC) - predicted dietary success or failure. Correlation analyses were applied to test whether symptoms of fructose malabsorption correlated with the H2 breath test measures. Finally, we evaluated whether cut-off-values of 40 or 60 parts per million (ppm) serve better than the test measure of 20 ppm to diagnose fructose malabsorption. RESULTS: When a fructose-free diet was administered it was found that 103 patients (41.9%) were complete responders, 116 (47.2%) were partial responders and 27 (11%) were non-responders. The H2 breath test with the 20 ppm cut-off-value, that is, the maximum H2 level, the maximum increase in H2, and the AUC did not predict dietary response (all 95% CI ns). This was also the case when using 40 or 60 ppm as cut-off-values (all 95% CI ns). Abdominal pain during the test correlated significantly with the AUC. Diarrhoea and bloating correlated significantly with the AUC, the maximum H2 level and the maximum increase in H2 (p < 0.05). CONCLUSIONS: The H2 breath test produced no predictive value for the fructose-free diet outcomes; its value as a predictive test is therefore questionable. However, the symptoms of fructose malabsorption correlated significantly with the H2 breath test measures, and this is an indication that there is at least a degree of validity of the H2 breath test beyond the simple detection or exclusion of fructose malabsorption.

High Prevalence of Pathological Hydrogen Breath Tests in Patients with Functional Dyspepsia.

BACKGROUND/AIMS: The aim of the study is to investigate the frequency of pathological hydrogen breath tests (HBT) in patients with clinical features of functional dyspepsia (FD) meeting the Rome criteria and normal testing of upper endoscopy and abdominal sonography. METHODS: We retrospectively included patients who underwent HBT (lactose, fructose, or glucose) between 2006 and 2012 and who had symptoms of FD. Patients were divided into 2 groups according to medical history and diagnostic results: (I) patients with suspected FD according to the Rome III criteria and (II) patients with an alternative diagnosis such as gastroesophageal reflux disease (GERD) or Crohn's disease (CD). RESULTS: A total of 207/404 patients were assigned to the FD group and 44.4% of these had at least 1 positive HBT and thus more frequently than patients with GERD (20.7%; n = 111; p < 0.001) and with CD (31.7%; n = 63; p = 0.07). Lactose and fructose HBT, but not glucose HBT, occurred significantly more frequently with pathological results than in patients with GERD (p = 0.02; p = 0.002). The probability of a positive HBT increased significantly with increasing number of performed HBT (p < 0.001). CONCLUSION: We suggest that HBT should be considered in the clinical management of patients with suspected FD. In cases of positive HBTs, a potential causal therapy can be initiated.

Fructose malabsorption in asymptomatic children and in patients with functional chronic abdominal pain: a prospective comparative study.

The objective of this prospective cohort study was to compare fructose malabsorption in patients with functional chronic abdominal pain and in healthy children. The sample was divided into two groups: asymptomatic children and pain-predominant functional gastrointestinal disorders according to the Rome IV criteria. All children were tested for fructose malabsorption by a standardized breath hydrogen test. Hydrogen and methane were measured and the test was presumed positive when it exceeded 20 ppm above baseline. If positive, patients were given a low-fructose diet and the response was evaluated. One hundred five children were included (34 healthy children, 71 with functional chronic abdominal pain), with similar demographic characteristics in both groups (35.2% male, age 9.5 ± 2.8 years). Hydrogen levels in breath were tested through a hydrogen test for fructose demonstrating malabsorption in 58.8% of healthy children (95%CI 40.8%-76.8%) and in 40.8% of children with chronic abdominal pain (95%CI 28.7%-53.0%), removing those who had bacterial overgrowth. Twenty-one of 31 patients with symptoms and a positive test (72.4%) reported an improvement on a low-fructose diet.Conclusion: Fructose malabsorption is more common in asymptomatic children than in patients with chronic abdominal pain. Better standardized test conditions are necessary to improve accuracy of diagnosis before using this test in clinical practice. What is Known: • Although fructose malabsorption is believed to be related with chronic abdominal pain, high-quality evidence is lacking. • Concerns have raised regarding the use of breath hydrogen test for fructose malabsorption in children with chronic abdominal pain. What is New: • Fructose malabsorption is not more common in children with pain-predominant functional gastrointestinal disorders than in asymptomatic children. • Improvement in symptoms with low-fructose diet may indicate that, although patients with pain-predominant functional gastrointestinal disorders did not have a higher percentage of malabsorption, they had greater fructose intolerance.

Relationship Between Abdominal Symptoms and Fructose Ingestion in Children with Chronic Abdominal Pain.

BACKGROUND: Limited valid data are available regarding the association of fructose-induced symptoms, fructose malabsorption, and clinical symptoms. AIM: To develop a questionnaire for valid symptom assessment before and during a carbohydrate breath test and to correlate symptoms with fructose breath test results in children/adolescents with functional abdominal pain. METHODS: A Likert-type questionnaire assessing symptoms considered relevant for hydrogen breath test in children was developed and underwent initial validation. Fructose malabsorption was determined by increased breath hydrogen in 82 pediatric patients with functional abdominal pain disorders; fructose-induced symptoms were quantified by symptom score ≥2 and relevant symptom increase over baseline. The results were correlated with clinical symptoms. The time course of symptoms during the breath test was assessed. RESULTS: The questionnaire exhibited good psychometric properties in a standardized assessment of the severity of carbohydrate-related symptoms. A total of 40 % (n = 33) had malabsorption; symptoms were induced in 38 % (n = 31), but only 46 % (n = 15) with malabsorption were symptomatic. There was no significant correlation between fructose malabsorption and fructose-induced symptoms. Clinical symptoms correlated with symptoms evoked during the breath test (p < 0.001, r2 = 0.21) but not with malabsorption (NS). Malabsorbers did not differ from non-malabsorbers in terms of symptoms during breath test. Symptomatic patients had significantly higher pain and flatulence scores over the 9-h observation period (p < 0.01) than did nonsymptomatic patients; the meteorism score was higher after 90 min. CONCLUSIONS: Fructose-induced symptoms but not fructose malabsorption are related to increased abdominal symptoms and have distinct timing patterns.

Intakes of apple juice, fruit drinks and soda are associated with prevalent asthma in US children aged 2-9 years.

OBJECTIVE: High soft drink consumption has been linked with asthma. Anecdotal evidence links high-fructose corn syrup with asthma. The receptor of advanced glycation end products (RAGE) has emerged as a mediator of asthma. The objectives of the present study were to: (i) assess the correlation between intake of beverages containing excess free fructose (EFF beverages) and asthma in children; and (ii) epidemiologically test the mechanistic hypothesis that intake of high EFF beverages, such as apple juice or beverages sweetened with high-fructose corn syrup, is associated with increased risk of asthma. This hypothesis is based on the possible effect of increases in the in situ intestinal formation of advanced glycation end products (enFruAGE) with EFF, which may be absorbed and play a role in RAGE-mediated asthma. DESIGN: We examined cross-sectional associations between beverage intake and self-reported current or history of asthma. Exposure variables were EFF beverages, including apple juice (AJ), non-diet soft drinks (ndSD) and fruit drinks (FD). Orange juice (OJ), not an EFF beverage, was included as a comparison. Rao-Scott χ(2) analysis was used for prevalence differences and logistic regression for associations, adjusted for age, sex, race/ethnicity, BMI and total energy intake. SETTING: Data are from the National Health and Nutrition Examination Survey 2003-2006, a nationally representative survey. SUBJECTS: US children (n 1961) aged 2-9 years with complete responses on the dietary frequency questionnaire. RESULTS: Intakes of EFF beverages were significantly associated with asthma in 2-9-year-olds. Adjusted odds of asthma in children consuming EFF beverages ≥5 times/week was more than five times that in children consuming these beverages ≤1 time/month (OR=5·29, P=0·012). Children consuming AJ ≥5 times/week v. ≤1 time/month, adjusted for the other beverages, were more than twice as likely to have asthma (OR=2·43, P=0·035). In contrast, there was a tendency for OJ to be protective. CONCLUSIONS: These results support the hypothesis that intake of high EFF beverages, including AJ and beverages sweetened with high-fructose corn syrup, is associated with asthma in children aged 2-9 years. Results support the mechanistic hypothesis that enFruAGE may be an overlooked contributor to asthma in children. Longitudinal studies are needed to provide evidence of causal association.

[Food intolerances caused by enzyme defects and carbohydrate malassimiliations : Lactose intolerance and Co]. / Lebensmittelunverträglichkeiten durch Enzymdefekte und Zuckerverwertungsstörungen : Laktoseintoleranz und Co.

Apart from allergic conditions, carbohydrate malassimiliations (sugar metabolism disorders) are classified within the group of food intolerances. These dose-dependent, yet non-immunological reactions require gastroenterological or internal diagnosis following nutritional therapy. Intolerances to carbohydrates such as lactose (milk sugar) and fructose (fruit sugar) in addition to sugar alcohols (sorbitol, mannitol, lactitol etc.) have been gaining increasing attention in recent decades as they are the cause of a wide range of gastrointestinal symptoms. There are currently various options for both diagnosis and therapy that differ notably in terms of effort, costs, and efficiency. Nutritional change and patient education are the bases of therapy. Non-observance of the trigger will result in increasing complaints and possibly even more infections, e.g., diverticula, rectal disorders, bacterial miscolonization, bile acid malabsorption). For an optimal therapy, the following sugar metabolism disorders have to be differentiated: hypolactasia versus lactose maldigestion, fructose malabsorption versus fructose overload, combined lactose and fructose intolerance, and isolated adverse reactions against sorbitol.For the medical conditions listed above, a three- or four-stage treatment regimen is recommended. Extensive dietary restrictions with regard to the relevant sugar, except for lactose, should not be maintained over a longer period of time.

Fecal Calprotectin Elevations Associated with Food Intolerance/Malabsorption Are Significantly Reduced with Targeted Diets.

Inflammatory bowel disease (IBD) involves two clinically defined entities, namely Crohn's disease and ulcerative colitis. Fecal calprotectin (FCAL) is used as a marker to distinguish between organic IBD and functional bowel disease in disorders of the irritable bowel syndrome (IBS) spectrum. Food components may affect digestion and cause functional abdominal disorders of the IBS spectrum. In this retrospective study, we report on FCAL testing to search for IBD in 228 patients with disorders of the IBS spectrum caused by food intolerances/malabsorption. Included were patients with fructose malabsorption (FM), histamine intolerance (HIT), lactose intolerance (LIT), and H. pylori infection. We found elevated FCAL values in 39 (17.1%) of 228 IBS patients with food intolerance/malabsorption and H. pylori infection. Within these, fourteen patients were lactose intolerant, three showed fructose malabsorption, and six had histamine intolerance. The others had combinations of the above conditions: five patients had LIT and HIT, two patients had LIT and FM, and four had LIT and H. pylori. In addition, there were individual patients with other double or triple combinations. In addition to LIT, IBD was suspected in two patients due to continuously elevated FCAL, and then found via histologic evaluation of biopsies taken during colonoscopy. One patient with elevated FCAL had sprue-like enteropathy caused by the angiotensin receptor-1 antagonist candesartan. When screening for study subjects concluded, 16 (41%) of 39 patients with initially elevated FCAL agreed to voluntarily control FCAL measurements, although symptom-free and -reduced, following the diagnosis of intolerance/malabsorption and/or H. pylori infection. After the initiation of a diet individualized to the symptomatology and eradication therapy (when H. pylori was detected), FCAL values were significantly lowered or reduced to be within the normal range.

A personalized management approach in disorders of the irritable bowel syndrome spectrum.

Symptoms of the disorders across the irritable bowel syndrome (IBS) spectrum include several different, usually postprandial, abdominal complaints. Up to date, dietary treatments of the IBS have neither been personalized nor diagnosed with sufficient scientific evidence. They have mostly been treated using 'one-size-fits-all' approaches. Such include exclusion diets, a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet, and gluten-free diets, lactose-free diets, a diet recommended by the UK National Institute for Health and Care Excellence, and a wheat-free diet. The exact pathophysiology of IBS disorders across the spectrum is still unclear. However, the symptom profile of IBS spectrum disorders seems similar to that of food intolerance/malabsorption syndromes. Celiac disease, fructose malabsorption, histamine intolerance and lactose intolerance represent food intolerance/malabsorption disorders based on the indigestion of sugars and/or proteins. Helicobacter pylori infection may potentially promote the development of IBS and, when facing a case of IBS-like symptoms, a search for intolerance/malabsorption and H. pylori should be added to find the correct treatment for the respective patient. This review will discuss why the 'one-size-fits-all' dietary approach in the treatment of complaints across the IBS spectrum cannot be successful. Hence, it will provide an overview of the most common overall dietary approaches currently used, and why those should be discouraged. Alternatively, a noninvasive diagnostic workup of the pathophysiologic factors of food intolerance/malabsorption in each patient with symptoms of the IBS spectrum is suggested. Additionally, if H. pylori is found, eradication therapy is mandatory, and if food intolerance/malabsorption is detected, an individual and personalized dietary intervention by a registered dietician is recommended.

Functional Abdominal Pain Disorders in Children May Be Associated with Food Intolerance/Malabsorption.

Functional abdominal pain disorders (FAPDs) are among the most common types of chronic pain disorders in children. FAPD symptoms are characterized by chronic abdominal pain and changed bowel movements. The pathophysiology of FAPDs in children is unknown, but these conditions may have an imprecise clinical overlap to food intolerance/malabsorption. We report on 51 consecutive children (23/28 males/females; median age 15.3 years) with investigated FAPDs from 2017 to 2022 in this retrospective pilot study. Small intestinal biopsies in children demonstrated the association of lactase and diamine oxidase (DAO), which prompted us to perform hydrogen (H2) breath tests for lactose intolerance (LIT) and determine serum DAO for the evaluation of histamine intolerance (HIT) in pediatric patients with FAPDs. To complete the food intolerance/malabsorption evaluation tests, we included a search for antibodies against tissue transglutaminase to find celiac disease (CD), performed H2 breath tests to detect fructose malabsorption (FM), and conducted a search for IgA antibodies against H. pylori infection. The results demonstrate that all 51 children evaluated were diagnosed with food intolerance/malabsorption and/or various combinations thereof. Seven children showed FM, eight of the children had HIT, and eight children had LIT. The other children had combinations: thirteen children (25.5%) had HIT and LIT, seven children (9.8%) had FM with HIT, five children (13.7%) had FM and LIT, and three children (5.9%) had a triple combination of FM, HIT, and LIT. By describing this method of personalized investigation for food intolerance/malabsorption in children with FAPDs, we demonstrate that functional abdominal pain disorders may be associated with food intolerance/malabsorption. After such diagnosis in this pediatric population, a registered dietitian helped to establish a reduction and/or exclusion diet individually tailored to their symptomatology.

Fructose Metabolism and Its Effect on Glucose-Galactose Malabsorption Patients: A Literature Review.

Glucose-galactose malabsorption is a rare inherited autosomal recessive genetic defect. A mutation in the glucose sodium-dependent transporter-1 gene will alter the transportation and absorption of glucose and galactose in the intestine. The defect in the SGLT-1 leads to unabsorbed galactose, glucose, and sodium, which stay in the intestine, leading to dehydration and hyperosmotic diarrhea. Often, glucose-galactose malabsorption patients are highly dependent on fructose, their primary source of carbohydrates. This study aims to investigate all published studies on congenital glucose-galactose malabsorption and fructose malabsorption. One hundred published studies were assessed for eligibility in this study, and thirteen studies were identified and reviewed. Studies showed that high fructose consumption has many health effects and could generate life-threatening complications. None of the published studies included in this review discussed or specified the side effects of fructose consumption as a primary source of carbohydrates in congenital glucose-galactose malabsorption patients.

Carbohydrate malabsorption in anorexia nervosa: a systematic review.

OBJECTIVES: Anorexia nervosa (AN) is an eating disorder accompanied by a low body mass index and (self-) restricted food intake. Nutritional limitations can cause complaints of the digestive system, because of a disturbed absorption of food components. The absorption of carbohydrates may be seriously affected and reduced to a minimum. On this basis, a possible connection between AN, and the prevalence of gastrointestinal symptoms due to malabsorption was examined. METHODS: For the systematic literature research with the aim of a better understanding of the topic the databases PubMed, Web of Science, Cochrane Library, Livivo and Google Scholar were used. RESULTS: After the manual selection process of 2215 retrieved studies, 89 full texts were read and according to the predetermined eligibility criteria, finally 2 studies on the monosaccharide fructose and disaccharide lactose were included in this review. CONCLUSION: Malabsorption is often observed in patients with AN. It may contribute to the gastrointestinal complaints reported by patients and hamper body weight regain. Among others, mucosal atrophy and duodenal transporter dysfunction are discussed as main reasons. In the future more studies on carbohydrate malabsorption related to low body weight as observed in AN are warranted and may be conducted rather in an outpatient setting.

People with anorexia nervosa (AN) may experience a preference for foods containing fewer calories but more carbohydrates, e.g. fruits and vegetables. The consequences of this food restriction and selection may include malabsorption of sugars such as fructose and lactose, the mechanism of which is incompletely understood. This may contribute to symptoms similar to those seen in people with lactose intolerance, e.g. bloating, and make it harder for people to eat recommended foods. This paper presents a comprehensive literature search for research on this topic. However, only two studies were identified which highlights that further investigation is needed to explore this clinically relevant field.

Helicobacter pylori infection and lactose intolerance increase expiratory hydrogen.

Infection with Helicobacter pylori (H.pylori) may cause dyspepsia and/or unexplained functional nonspecific, gastrointestinal complaints of the irritable bowel syndrome (IBS) spectrum. Hitherto, in H. pylori infected patients with symptoms of the IBS spectrum the occurrence of additional food intolerance/malabsorption is not evaluated. We used a retrospective analysis of charts from 548 patients who presented with gastrointestinal complaints of the irritable bowel syndrome spectrum. An enzyme-linked IgA immunosorbent assay or histologic evaluation of gastric mucosa were used to detect H. pylori infection. A hydrogen breath (H2) test was performed to evaluate fructose malabsorption (FM) and lactose intolerance (LIT). Serum diamine oxidase value of <10 U/ml and a response to a histamine-reduced diet was used to identify histamine intolerance (HIT). We found 293 patients infected with H. pylori, within these were 58 H. pylori patients with LIT, 23 H. pylori LIT patients with FM and 46 H. pylori LIT patients with HIT. Additionally, 13 H. pylori, lactose- and histamine intolerance patients also had FM. The Kruskal Wallis test and pairwise comparison were used to analyze differences of the area under the curve of expiratory hydrogen. In lactose H2 breath tests compared with LIT-only patients, LIT with H. pylori, LIT and H. pylori with HIT, LIT and H. pylori with FM showed significantly higher exhaled H2 levels (p=0.022). Pairwise comparison demonstrated H. pylori infected patients with LIT exhaled more H2 compared to LIT-only (p=0.029). H. pylori with lactose- and histamine intolerance, and H. pylori with lactose-, histamine intolerance and FM compared to H. pylori-only patients indicated a significantly higher occurrence of stomach pain during lactose H2 breath tests (p=0.012 and p=0.005, respectively). We demonstrate that LIT patients with high expiratory H2 levels in lactose breath tests may have H. pylori infection and possibly additional food intolerance/malabsorption. Subsequently, besides H. pylori eradication, a dietician is necessary for an individually tailored reduction- or exclusion diet of symptom triggering food components.

Case report: Carbohydrate malabsorption in inpatients with anorexia nervosa.

Background: Gastrointestinal (GI) complaints are frequently observed in patients who suffer from anorexia nervosa (AN). These symptoms may hamper treatment and weight regain and are often perceived as the cause, not the consequence, of the disease. Since carbohydrate malabsorption also produces these symptoms, this might underly or contribute to these complaints. So far, the role of carbohydrate malabsorption (fructose malabsorption and lactose intolerance) in AN has not yet been investigated. Methods: For this case series, inpatients with AN of restrictive type (n = 3), purging type (n = 3), and atypical AN (n = 1) conducted hydrogen breath tests with 25 g of fructose and 50 g of lactose to investigate carbohydrate malabsorption. Results were then analyzed in association with body mass index (BMI) and patient-reported outcomes (disordered eating, body image disturbances, anxiety, depressive symptoms, perceived stress, and GI complaints). Results: Based on the hydrogen breath test results, three of the seven female patients were classified as lactose intolerant and one presented fructose malabsorption. Both hydrogen curves for fructose (r = -0.632, p < 0.001) and lactose (r = -0.704, p < 0.001) showed a negative correlation with BMI. No association was observed between hydrogen values and patient-reported outcomes. Conclusion: In patients with AN, GI symptoms caused by intolerance of common monosaccharides and disaccharides may be an underestimated burden and should be considered in the diagnosis and therapy of patients with AN. Due to the observed correlation with BMI, GI complaints after ingestion of fructose or lactose likely develop with decreasing body weight and are potentially reversible with weight regain.

Theories behind the effect of starch­ and sucrose­reduced diets on gastrointestinal symptoms in irritable bowel syndrome (Review).

Increased amounts of starch and sugar have been added to the diet in the Western world during the last decades. Undigested carbohydrates lead to bacterial fermentation and gas production with diffusion of water, causing abdominal bloating, pain and diarrhea. Therefore, dietary advice is the first line of treatment of irritable bowel syndrome (IBS), a disease characterized by abdominal pain and altered bowel habits without any organic findings. Recently, a diet with a reduction of starch and sucrose led to a marked effect on gastrointestinal (GI) symptoms. The mechanism is unknown, but three possible mechanisms are presented in the present review. First, functional variants of the enzyme sucrase­isomaltase (SI) have been described in IBS. A subgroup of patients with IBS may thus suffer from partial SI deficiency with reduced digestion of starch and sucrose. Second, fructose absorption is less efficient than glucose absorption, which may lead to a physiological fructose malabsorption when ingesting high amounts of sucrose. A third mechanism is that high­sugar diets causing hyperglycemia, hyperinsulinemia and weight gain have led to painful neuropathy in animal models; whereas, improved metabolic control in humans has led to improvement of neuropathy. Starch­ and sucrose­reduced diets lead to decreased levels of C­peptide, insulin, gastric inhibitory peptide, leptin and weight reduction. These metabolic changes may reduce the excitability of the hypersensitive nervous system often found in IBS and, thereby, lead to the reduced symptoms found after the diet. In conclusion, further studies are needed to investigate the pathophysiology behind development of symptoms after starch and sucrose intake, and the mechanisms behind symptom relief after reduced intake.

No Correlation between Positive Fructose Hydrogen Breath Test and Clinical Symptoms in Children with Functional Gastrointestinal Disorders: A Retrospective Single-Centre Study.

Fructose malabsorption is regarded as one of the most common types of sugar intolerance. However, the correlation between gastrointestinal symptoms and positive results in fructose hydrogen breath tests (HBTs) remains unclear. The aim of this study was to assess the clinical importance of positive fructose HBT by correlating the HBT results with clinical features in children with various gastrointestinal symptoms. Clinical features and fructose HBT results were obtained from 323 consecutive children (2-18 years old, mean 10.7 ± 4.3 years) that were referred to the Tertiary Paediatric Gastroenterology Centre and diagnosed as having functional gastrointestinal disorders. A total of 114 out of 323 children (35.3%) had positive HBT results, of which 61 patients were females (53.5%) and 53 were males (46.5%). Children with positive HBT were significantly younger than children with negative HBT (9.0 vs. 11.6 years old; p < 0.001). The most frequent symptom among children with fructose malabsorption was recurrent abdominal pain (89.5%). Other important symptoms were diarrhoea, nausea, vomiting, and flatulence. However, no correlation between positive fructose HBT results and any of the reported symptoms or general clinical features was found. In conclusion, positive fructose HBT in children with functional gastrointestinal disorders can be attributed to their younger age but not to some peculiar clinical feature of the disease.