BACKGROUND & AIMS: The aim of this study was to investigate the effectiveness of oral treatment with a nonviable probiotic lysate (BL) of Escherichia coli (DSM 17252) and Enterococcus faecalis (DSM 16440) in patients with irritable bowel syndrome (IBS). METHODS: A phase IV, randomized, double-blind, placebo-controlled, multicenter (30 study sites), parallel group study was conducted in 389 patients of both sexes with IBS according to Rome III criteria. The treatment period was 26 weeks. The participants were allocated to either placebo or BL after a 2-week baseline period. The primary outcome was based on the European Medicines Agency IBS guideline: improvement in global assessment (GAI) and improvement in abdominal pain. RESULTS: Patients (BL, n = 191; placebo, n = 198) had similar baseline values and dropout rates. Overall, the response was similar between BL and placebo for IBS-GAI (17.4% and 14.4%, respectively; P = center dot 4787) and abdominal pain (42.0% and 35.4%, respectively; P = center dot 1419). Some secondary outcome measures and sensitivity analyses pointed toward potentially higher sensitivity of the abdominal pain measures in diarrhea-predominant IBS (IBS-D) but not the other subtypes. For the GAI, no subgroup differences were detected. For IBS-D, post hoc analyses for abdominal pain response over time and stool consistency showed potentially promising effects of BL. Finally, the treatment with BL was well-tolerated. CONCLUSIONS: BL is not effective across all IBS subtypes. However, BL may offer a treatment option for IBS-D that needs verification by an adequately powered drug trial; EudraCT-No.: 2012-002741-38.

BACKGROUND:Single-nucleotide polymorphisms (SNPs) of the serotonin type 3 receptor subunit (HTR3) genes have been associated with psychosomatic symptoms, but it is not clear whether these associations exist in irritable bowel syndrome (IBS). AIM:To assess the association of HTR3 polymorphisms with depressive, anxiety, and somatization symptoms in individuals with IBS. METHODS:In this retrospective study, 623 participants with IBS were recruited from five specialty centers in Germany, Sweden, the United States, the United Kingdom, and Ireland. Depressive, anxiety, and somatization symptoms and sociodemographic characteristics were collected. Four functional SNPs - HTR3A c.-42C>T, HTR3B c.386A>C, HTR3C c.489C>A, and HTR3E c.*76G>A - were genotyped and analyzed using the dominant and recessive models. We also performed separate analyses for sex and IBS subtypes. SNP scores were calculated as the number of minor alleles of the SNPs above. The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays. RESULTS:Depressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model (F depressive = 7.475, P depressive = 0.006; F anxiety = 6.535, P anxiety = 0.011). A higher SNP score (range 0-6) was linked to a worsened depressive symptoms score (F = 7.710, P-linear trend = 0.006) in IBS. The potential relevance of the HTR3C SNP was corroborated, showing changes in the expression level of 5-HT3AC variant receptors. CONCLUSION:We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS. The SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS.

Die chologene Diarrho ist eine der haufigsten nicht diagnostizierten Ursachen der chronischen Diarrho, der zahlreiche verschiedene Pathophysiologien zugrunde liegen konnen. Auch nach Ausschlussdiagnostik der haufigeren Ursachen verbleiben bis zu 5% der Bevolkerung von einer ungeklarten chronischen Diarrho betroffen. In diesem Kollektiv findet sich in bis zu 50% als Ursache eine chologene Diarrho. Abstract The various pathophysiologies leading to bile acid diarrhea are well characterized. In this way, bile acid diarrhea can be divided into primary, secondary and tertiary subtypes. Common to all causes is the increased amount of bile acids in the colon and in the faeces and the resulting secretory-osmotic diarrhea, in more severe forms in combination with steatorrhea. The diagnosis of bile acid diarrhea follows a clear algorithm which, in addition to the search for the cause and possibly a therapeutic trial, recognizes the (75) SeHCAT test as the reference method for the detection of an increased loss of bile acids. In view of the chronic nature of the symptoms and the need for permanent, lifelong therapy, the use of a one-time, reliable diagnostic test is justified, though the test is currently only available at a few centers. In addition to the treatment of identifiable underlying diseases, the current treatment includes the use of drugs that bind bile acids, with additional nutritional recommendations and vitamin substitutions. The present review article summarizes the pathophysiology and importance of bile acid diarrhea and discusses the current approach towards diagnosis and treatment.

Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT 3 receptor family. 5-HT 3 Rs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular. Moreover, 5-HT 3 R antagonists are beneficial in the treatment of diarrhea predominant IBS (IBS-D). We previously reported on functionally relevant SNPs in HTR3A c.-42C > T (rs1062613), HTR3C p.N163K (rs6766410), and HTR3E c.*76G > A (rs56109847 = rs62625044) being associated with IBS-D, and the HTR3B variant p.Y129S (rs1176744) was also described within the context of IBS. We performed a multi-center study to validate previous results and provide further evidence for the relevance of HTR3 genes in IBS pathogenesis. Therefore, genotype data of 2682 IBS patients and 9650 controls from 14 cohorts (Chile, Germany (2), Greece, Ireland, Spain, Sweden (2), the UK (3), and the USA (3)) were taken into account. Subsequent meta-analysis confirmed HTR3E c.*76G > A (rs56109847 = rs62625044) to be associated with female IBS-D (OR = 1.58; 95% CI (1.18, 2.12)). Complementary expression studies of four GI regions (jejunum, ileum, colon, sigmoid colon) of 66 IBS patients and 42 controls revealed only HTR3E to be robustly expressed. On top, HTR3E transcript levels were significantly reduced in the sigma of IBS patients ( p = 0.0187); more specifically, in those diagnosed with IBS-D ( p = 0.0145). In conclusion, meta-analysis confirmed rs56109847 = rs62625044 as a risk factor for female IBS-D. Expression analysis revealed reduced HTR3E levels in the sigmoid colon of IBS-D patients, which underlines the relevance of HTR3E in the pathogenesis of IBS-D.

Die chologene Diarrhö ist eine der häufigsten nicht diagnostizierten Ursachen der chronischen Diarrhö, der zahlreiche verschiedene Pathophysiologien zugrunde liegen können. Auch nach Ausschlussdiagnostik der häufigeren Ursachen verbleiben bis zu 5% der Bevölkerung von einer ungeklärten chronischen Diarrhö betroffen. In diesem Kollektiv findet sich in bis zu 50% als Ursache eine chologene Diarrhö.

Irritable bowel syndrome (IBS) is a gut-brain disorder in which symptoms are shaped by serotonin acting centrally and peripherally. The serotonin transporter gene SLC6A4 has been implicated in IBS pathophysiology, but the underlying genetic mechanisms remain unclear. We sequenced the alternative P2 promoter driving intestinal SLC6A4 expression and identified single nucleotide polymorphisms (SNPs) that were associated with IBS in a discovery sample. Identified SNPs built different haplotypes, and the tagging SNP rs2020938 seems to associate with constipation-predominant IBS (IBS-C) in females. rs2020938 validation was performed in 1978 additional IBS patients and 6,038 controls from eight countries. Meta-analysis on data from 2,175 IBS patients and 6,128 controls confirmed the association with female IBS-C. Expression analyses revealed that the P2 promoter drives SLC6A4 expression primarily in the small intestine. Gene reporter assays showed a functional impact of SNPs in the P2 region. In silico analysis of the polymorphic promoter indicated differential expression regulation. Further follow-up revealed that the major allele of the tagging SNP rs2020938 correlates with differential SLC6A4 expression in the jejunum and with stool consistency, indicating functional relevance. Our data consolidate rs2020938 as a functional SNP associated with IBS-C risk in females, underlining the relevance of SLC6A4 in IBS pathogenesis.

Several studies have implied a role of brain-derived neurotrophic factor (BDNF) in abdominal pain modulation in irritable bowel syndrome (IBS). The aim of this study was to establish BDNF protein expression in human colonic biopsies and to show variation in IBS compared to controls. BDNF protein and mRNA levels were correlated with IBS symptom severity based on the IBS-symptom severity score (IBS-SSS). Biopsies from the descending colon and IBS-SSS were obtained from 10 controls and 20 IBS patients. Total protein of biopsies was extracted and assessed by ELISA and Western Blot. Total mRNA was extracted and gene expression measured by nCounter analysis. In IBS patients, symptom severity scores ranged from 124 to 486 (mean ± sem: 314.2 ± 21.2, >300 represents severe IBS) while controls ranged from 0 to 72 (mean ± sem: 27.7 ± 9.0, <75 represents healthy subjects, p < 0.001). IBS patients reported significantly more food malabsorption, former abdominal surgery and psychiatric comorbidities. BDNF protein was present in all samples and did not differ between IBS and controls or sex. Subgroup analysis showed that female IBS patients expressed significantly more BDNF mRNA compared to male patients (p < 0.05) and male IBS-D patients had higher IBS symptom severity scores and lower BDNF mRNA and protein levels compared to male controls (p < 0.05). Scatter plot showed a significant negative correlation between IBS-SSS and BDNF mRNA levels in the cohort of male IBS-D patients and their male controls (p < 0.05). We detected a high proportion of gastrointestinal surgery in IBS patients and confirmed food intolerances and psychiatric diseases as common comorbidities. Although in a small sample, we demonstrated that BDNF is detectable in human descending colon, with higher BDNF mRNA levels in female IBS patients compared to males and lower mRNA and protein levels in male IBS-D patients compared to male controls. Further research should be directed toward subgroups of IBS since their etiologies might be different.

BACKGROUND & AIMS: Swallowed topical-acting corticosteroids are recommended as first-line therapy for eosinophilic esophagitis (EoE). Asthma medications not optimized for esophageal delivery are sometimes effective, although given off-label. We performed a randomized, placebo-controlled trial to assess the effectiveness and tolerability of a budesonide orodispersible tablet (BOT), which allows the drug to be delivered to the esophagus in adults with active EoE. METHODS: We performed a double-blind, parallel study of 88 adults with active EoE in Europe. Patients were randomly assigned to groups that received BOT (1 mg twice daily; n = 59) or placebo (n = 29) for 6 weeks. The primary end point was complete remission, based on clinical and histologic factors, including dysphagia and odynophagia severity <= 2 on a scale of 0-10 on each of the 7 days before the end of the double-blind phase and a peak eosinophil count <5 eosinophils/high power field. Patients who did not achieve complete remission at the end of the 6-week double-blind phase were offered 6 weeks of open-label treatment with BOT (1 mg twice daily). RESULTS: At 6 weeks, 58% of patients given BOT were in complete remission compared with no patients given placebo (P < .0001). The secondary end point of histologic remission was achieved by 93% of patients given BOT vs no patients given placebo (P < .0001). After 12 weeks, 85% of patients had achieved remission. Six-week and 12-week BOT administration were safe and well tolerated; 5% of patients who received BOT developed symptomatic, mild candida, which was easily treated with an oral antifungal agent. CONCLUSIONS: In a randomized trial of adults with active EoE, we found that budesonide oral tablets were significantly more effective than placebo in inducing clinical and histologic remission. Eudra-CT number 2014-001485-99;

Background Irritable bowel syndrome (IBS) is associated with reduced quality of life and high healthcare costs. This study aimed to assess the prevalence and risk factors for IBS in a general adult population. Methods The Study of Health in Pomerania (SHIP) is a population-based cohort study in northeastern Germany. SHIP-Trend-0 participants enrolled from 2008 to 2012 were grouped according to Rome III criteria (main criteria: abdominal discomfort or crampy or bloating pain for at least six months plus 2/3 additional criteria). Factors associated with IBS were assessed using survey-weighted backward stepwise logistic regression. Key Results The final data set included 4194 records. IBS prevalence was 3.5% (3.0%-4.2%). Unemployment (OR: 2.02, 1.26-3.21), headaches (OR: 2.37, 1.59-3.52), mental quality of life (OR: 0.95 per unit increase, 0.93-0.97), and interactions between gender and physical quality of life (P = 0.004) and gender and alexithymia (P = 0.002) predicted IBS probability. The model resulted in a good discrimination (area under the curve = 75.4%) and model fit (F = 0.72, P = 0.69). History of depression (OR: 2.77, 1.94-3.95), back pain (OR: 2.38, 1.69-3.35), early trauma (OR: 1.03, 1.02-1.04), and duration of inpatient treatment within the last twelve months (OR: 1.02, 1.01-1.04) lost their significance in multivariable analysis. Conclusions & Inferences IBS prevalence was relatively low compared to other studies. Factors predicting IBS were of biological, psychological, and social nature. The association between IBS and pain in different areas of the body indicates a potential underlying complex somatic symptom disorder.

ZusammenfassungIn den letzten Jahren häuft sich die Nennung der Nicht-Zöliakie-Gluten-/Weizen-Sensitivität (NCGS, „non celiac gluten sensitivity“) sowohl in den Medien, aber auch in Fachkreisen. Die Existenz und die möglichen verantwortlichen Trigger werden kontrovers diskutiert. Drei internationale Expertentreffen mit Empfehlungen zur NCGS waren nicht unabhängig organisiert und wenig transparent bezüglich potenzieller Interessenkonflikte der Teilnehmer.Die vorliegende Stellungnahme enthält wichtige Überlegungen aus allergologischer und ernährungsphysiologischer Sicht: (1) Aufgrund häufiger Selbstdiagnosen, unklarer Prävalenz und unbestätigter Ätiologie der NCGS sind validierte Diagnosekriterien und/oder verlässliche Biomarker notwendig. (2) Infolge hoher Nocebo- und häufiger Placebo-Effekte konnte Gluten bislang nicht sicher als Auslöser einer NCGS identifiziert werden. Doppelblinde, placebokontrollierte Provokationen (DBPCFC: double-blind, placebo-controlled food challenge) sind bei Verdacht auf NCGS nur in modifizierter Form (verändertes Verhältnis von Placebo zu Verum) geeignet. (3) Zahlreiche Störgrößen (Confounder) erschweren die Bewertung subjektiver Symptome unter glutenarmer/-freier Kost. Letztere kann je nach Lebensmittelauswahl (z. B. vermehrt Gemüse mit löslichen Ballaststoffen) physiologische Verdauungseffekte bewirken und gastrointestinale Transitzeiten unabhängig vom Glutenverzicht verändern. (4) Streng glutenfreie Kost ist bei einer gesicherten Zöliakie wissenschaftlich begründet und unerlässlich. Bei einem medizinisch unbegründeten Glutenverzicht überwiegen jedoch potenzielle Nachteile und Risiken. (5) Aktuell kann wegen fehlender überzeugender Diagnosekriterien bei Verdacht einer NCGS ausschließlich eine sorgfältige Differenzialdiagnostik empfohlen werden. Hierzu gehören eine sorgfältige Anamnese, einschließlich eines Ernährungs- und Symptomtagebuchs, eine allergologische Diagnostik und ein sicherer Ausschluss einer Zöliakie.Wir befürworten ein derartiges strukturiertes Vorgehen, da ohne eine medizinisch gesicherte Diagnose die Durchführung einer längeren Glutenkarenz nicht zu empfehlen ist. Englische Fassung http://link.springer.com/journal/40629

Within the last decade, non-celiac gluten/ wheat sensitivity (NCGS) has been increasingly discussed not only in the media but also among medical specialties. The existence and the possible triggers of NCGS are controversial. Three international expert meetings which proposed recommendations for NCGS were not independently organized and only partially transparent regarding potential conflicts of interest of the participants. The present position statement reflects the following aspects about NCGS from an allergist’s and nutritionist’s point of view: (A) Validated diagnostic criteria and/or reliable biomarkers are still required. Currently, this condition is frequently self-diagnosed, of unknown prevalence and non-validated etiology. (B) Gluten has not been reliably identified as an elicitor of NCGS because of high nocebo and placebo effects. Double-blind, placebo-controlled provocation tests are of limited value for the diagnosis of NCGS and should be performed in a modified manner (changed relation of placebo and active substance). (C) Several confounders hamper the assessment of subjective symptoms during gluten-reduced or gluten-free diets. Depending on the selection of food items, e.g., an increased vegetable intake with soluble fibers, diets may induce physiological digestive effects and can modify gastrointestinal transit times independent from the avoidance of gluten. (D) A gluten-free diet is mandatory in celiac disease based on scientific evidence. However, a medically unjustified avoidance of gluten may bear potential disadvantages and risks. (E) Due to a lack of diagnostic criteria, a thorough differential diagnostic work-up is recommended when NCGS is suspected. This includes a careful patient history together with a food-intake and symptom diary, if necessary an allergy diagnostic workup and a reliable exclusion of celiac disease. We recommend such a structured procedure since a medically proven diagnosis is required before considering the avoidance of gluten.

Irritable bowel syndrome (IBS) is a gut-brain disorder involving alterations in intestinal sensitivity and motility. Serotonin 5-HT 4 receptors are promising candidates in IBS pathophysiology since they regulate gut motor function and stool consistency, and targeted 5-HT 4 R selective drug intervention has been proven beneficial in subgroups of patients. We identified a single nucleotide polymorphism (SNP) (rs201253747) c.*61 T > C within the 5-HT 4 receptor gene HTR4 to be predominantly present in diarrhoea-IBS patients (IBS-D). It affects a binding site for the miR-16 family and miR-103/miR-107 within the isoforms HTR4b/i and putatively impairs HTR4 expression. Subsequent miRNA-profiling revealed downregulation of miR-16 and miR-103 in the jejunum of IBS-D patients correlating with symptoms. In vitro assays confirmed expression regulation via three 3′UTR binding sites. The novel isoform HTR4b_2 lacking two of the three miRNA binding sites escapes miR-16/103/107 regulation in SNP carriers. We provide the first evidence that HTR4 expression is fine-tuned by miRNAs, and that this regulation is impaired either by the SNP c.*61 T > C or by diminished levels of miR-16 and miR-103 suggesting that HTR4 might be involved in the development of IBS-D.

Eine immunologische Unverträglichkeit gegen Nahrungsmittel (NM) ist als Nahrungsmittelallergie (NMA) definiert. Hierbei handelt es sich meist um durch Immunglobuline der Klasse E (IgE) bedingte Soforttypreaktionen (Typ-I-Allergie) mit möglicher Beteiligung von Schleimhäuten, Haut, Atemwegen, Verdauungstrakt und Kreislauf. Primäre NMA beruhen auf (vorhergegangener) IgE-Sensibilisierung gegen tierische (z. B. in Kuhmilch, Hühnerei) oder pflanzliche Proteine (z. B. in Erdnuss, Haselnuss oder Weizen). Bei sekundären NMA reagiert IgE gegen Pollenproteine (z. B. Birke) auf strukturell ähnliche NM-Proteine (mit Kreuzallergie auf Kern- und Steinobst). Nichtimmunologische NM-Unverträglichkeiten sind meist Kohlenhydratmalassimilationen (z. B. Laktoseintoleranz, Fruktosemalabsorption) und ganz selten Pseudoallergien (z. B. gegen Aroma-, Farb-, Konservierungsstoffe), die bevorzugt bei Patienten mit chronischer Urtikaria auftreten. Häufige Verdauungsprobleme beruhen meist auf funktionellen Beschwerden (z. B. Reizdarmsyndrom), selten auf entzündlichen Darmerkrankungen (z. B. Zöliakie). Histaminintoleranz, Glutenhypersensitivität und angebliche NM-Typ-III-Allergien sind umstrittene Diagnosen. Die dargestellten Krankheitsbilder und -modelle besitzen für die Betroffenen, das Gesundheitssystem und die Gesellschaft unterschiedlichste Bedeutung.

Immunologically mediated hypersensitivity to foods is defined as food allergy, mainly due to immunglobulins of class E (IgE) triggering immediate reactions (type I hypersensitivity) with possible involvement of mucosa, skin, airways, intestinal tract, and the vascular system. Primary food allergy is based on (early) IgE sensitization against animal (e.g., cow's milk, hen's eggs) or plant proteins (e.g. peanut, hazelnut or wheat). In the case of secondary food allergies, IgE against pollen proteins (e.g., birch) reacts to structurally related food proteins (with cross-reactions to stone and pit fruits). Non-immunological food intolerance reactions are mostly based on carbohydrate malassimilation (e.g., lactose intolerance, fructose malabsorption) and are rarely due to pseudo-allergies (e.g., flavors, dyes, preservatives) primarily in patients with chronic urticaria. Common intestinal symptoms are mainly due to functional disorders (e.g., irritable bowel disease), rarely because of inflammatory intestinal diseases (e.g., celiac disease). Histamine intolerance, gluten hypersensitivity, and so-called food type III hypersensitivities are controversial diagnoses. The aforementioned disease entities/models are of variable importance for the affected individuals, the public health system, and society in general.

TO THE EDITOR: With great interest we have been following the discussion about our study published in Journal of Neurogastroenterology and Motility.1 We highly estimate the recent constructive comments expressed by the authors Erdogan and colleagues2 and would like to make some conclusive remarks. We fully agree with the authors that all patients with irritable bowel syndrome (IBS)-like symptoms should undergo breath testing and have specifically stated this in our manuscript. Thus, we are not sure where Erdogan et al2 got the notion that such tests should only be performed for research purposes. We furthermore agree with Erdogan et al2 that 2 consecutive breath tests are impractical, especially considering the bothersome symptoms that patients experience during and after testing. Therefore, we favor the breath test with 50 g fructose. From our yet unpublished data we know that H2 breath tests with 50 g fructose identify patients with IBS-like symptoms who will benefit from a fructose-reduced diet. If only 25 g tests were performed, an important subgroup (the ones with symptomatic 50 g breath test) would be missed although they greatly benefit from a detailed dietary counseling, while patients with positive 25 g breath test already benefit from brief dietary advice as shown by a decline in gastrointestinal (GI) symptoms, improved quality of life and state of health. In patients with severe fructose malabsorption only the detailed dietary advice regimen resulted in improvement of GI symptoms and perceived state of health. This is our rationale to perform a breath test with 50 g of fructose. The German consensus paper on clinically relevant breath tests in gastroenterological diagnostics does not always recommend a test with 50 g. It points out that in case of highly suspected fructose malabsorption, the high dose test should be performed first and in case of a positive outcome, an additional 25 g test enhances specificity.3 On the other hand, the rationale to start with the low dose is that healthy volunteers almost never malabsorb 25 g. Thus, the test has an excellent specificity because, according to test criteria, there are rarely false positives. However, we feel that the low dose test lacks sensitivity because a proportion of negative low dose breath testers will still respond to a fructose elimination diet. To deal with the lower specificity in the high dose test, observing symptoms during the test can help: increased H2 excretion combined with typical symptoms triggered by the high dose challenge is a good criterion to distinguish between true and false positive patients, and healthy volunteers barely report symptoms even though they may have elevated H2 excretion.4 Some healthy subjects and patients with IBS-like symptoms are able to fully absorb 50 g of fructose because otherwise, every test person would have significant H2 excretion and symptoms. In our study 64% were symptomatic fructose malabsorbers with a 50 g test dose, which in reverse implies that 36% of patients with unclear abdominal discomfort were able to absorb 50 g of fructose without clinical symptoms. We disagree with the authors that amounts > 25 g of fructose are nowadays not consumed at once. As recently outlined, a 16-oz bottle of apple juice may contain > 30 g fructose and a 22-oz soft drink could contain approximately 30 g to 40 g depending on the percent fructose in the corn syrup sweetener,5,6 both representing liquids regularly consumed by a large proportion of the population. As clinicians we will accept false positives. They may undergo a 4–6 weeks dietary trial and not respond. But it is unpleasant to exclude patients, in whom most of the treatments have failed, from a fructose elimination diet that works most of the time in these patients because their diagnosis was missed. Thus, we find it more appropriate to use the high dose test with 50 g because we feel that it is clinically more relevant.

BACKGROUND/AIMS:Carbohydrate malabsorption is frequent in patients with functional gastrointestinal disorders and in healthy volunteers and can cause gastrointestinal symptoms mimicking irritable bowel syndrome (IBS). The aim of this study was to investigate the prevalence of symptomatic lactose and fructose malabsorption in a large population of patients with IBS-like symptoms based on Rome II criteria.METHODS:Patients with unclear abdominal discomfort (n = 2,390) underwent lactose (50 g) and fructose (50 g) hydrogen (H2) breath tests and depending on the results further testing with 25 g fructose or 50 g glucose, or upper endoscopy with duodenal biopsies. Additionally, this population was investigated regarding the prevalence of small intestinal bacterial overgrowth (SIBO) based on glucose breath test and celiac disease.RESULTS:Of the 2,390 patients with IBS-like symptoms, 848 (35%) were symptomatic lactose malabsorbers and 1,531 (64%) sympto-matic fructose malabsorbers. A combined symptomatic carbohydrate malabsorption was found in 587 (25%) patients. Severe fructose malabsorbers (pathologic 25 g fructose test) exhaled significantly higher H2 concentrations in the 50 g test than pa-tients with negative 25 g fructose test (P < 0.001). Out of 460/659 patients with early significant H2 increase in the lactose and fructose test who underwent a glucose breath test, 88 patients had positive results indicative of SIBO and they were sig-nificantly older than patients with negative test result (P < 0.01). Celiac disease was found in 1/161 patients by upper endoscopy.CONCLUSIONS:Carbohydrate malabsorption is a frequent but underestimated condition in patients with IBS-like symptoms although diagnosis can be easily confirmed by H2 breath testing.