Behavioral therapy is superior to follow-up without intervention in patients with supragastric belching-A randomized study.

BACKGROUND: Behavioral therapy (BT) has been proven effective in the treatment of supragastric belching (SGB) in open studies. The aim was to compare BT to follow-up without intervention in patients with SGB in a randomized study. METHODS: Forty-two patients were randomized to receive 5 sessions of BT, comprising diaphragmatic breathing exercises, or to follow-up without intervention. Patients were evaluated at 6 months, at which point the control group was also offered BT and evaluated after another 6 months. The frequency and intensity of belching and mental well-being were evaluated with a visual analog scale (VAS). Depression, anxiety, and health-related quality of life (HRQoL) were evaluated with four questionnaires: BDI, BAI, 15D, and RAND-36. KEY RESULTS: The frequency and intensity of SGB were significantly lower in the therapy group (n = 19) than in the control group (n = 18) at the 6-month control (p < 0.001). When all patients (n = 36) were evaluated 6 months after BT, in addition to relief in the frequency and intensity of belching (p < 0.001), mental well-being had also improved (p < 0.05). Of all 36 patients, 27(75%) responded to BT. Depression scores were lower after therapy (p < 0.05). Only minor changes occurred in anxiety and HRQoL. CONCLUSIONS AND INFERENCES: Behavioral therapy is superior to follow-up without intervention in patients with SGB in reducing belching and depression; it also improves mental well-being but has only a modest effect on anxiety and HRQoL.

A Randomized Trial of a Transglutaminase 2 Inhibitor for Celiac Disease.

BACKGROUND: In celiac disease, small intestinal transglutaminase 2 causes deamidation of glutamine residues in gluten peptides, which enhances stimulation of T cells and leads to mucosal injury. Inhibition of transglutaminase 2 is a potential treatment for celiac disease. METHODS: In a proof-of-concept trial, we assessed the efficacy and safety of a 6-week treatment with ZED1227, a selective oral transglutaminase 2 inhibitor, at three dose levels as compared with placebo, in adults with well-controlled celiac disease who underwent a daily gluten challenge. The primary end point was the attenuation of gluten-induced mucosal damage, as measured by the ratio of villus height to crypt depth. Secondary end points included intraepithelial lymphocyte density, the Celiac Symptom Index score, and the Celiac Disease Questionnaire score (for assessment of health-related quality of life). RESULTS: Of the 41 patients assigned to the 10-mg ZED1227 group, the 41 assigned to the 50-mg group, the 41 assigned to the 100-mg group, and the 40 assigned to the placebo group, 35, 39, 38, and 30 patients, respectively, had adequate duodenal-biopsy samples for the assessment of the primary end point. Treatment with ZED1227 at all three dose levels attenuated gluten-induced duodenal mucosal injury. The estimated difference from placebo in the change in the mean ratio of villus height to crypt depth from baseline to week 6 was 0.44 (95% confidence interval [CI], 0.15 to 0.73) in the 10-mg group (P = 0.001), 0.49 (95% CI, 0.20 to 0.77) in the 50-mg group (P<0.001), and 0.48 (95% CI, 0.20 to 0.77) in the 100-mg group (P<0.001). The estimated differences from placebo in the change in intraepithelial lymphocyte density were -2.7 cells per 100 epithelial cells (95% CI, -7.6 to 2.2) in the 10-mg group, -4.2 cells per 100 epithelial cells (95% CI, -8.9 to 0.6) in the 50-mg group, and -9.6 cells per 100 epithelial cells (95% CI, -14.4 to -4.8) in the 100-mg group. Use of the 100-mg dose may have improved symptom and quality-of-life scores. The most common adverse events, the incidences of which were similar across all groups, were headache, nausea, diarrhea, vomiting, and abdominal pain. Rash developed in 3 of 40 patients (8%) in the 100-mg group. CONCLUSIONS: In this preliminary trial, treatment with ZED1227 attenuated gluten-induced duodenal mucosal damage in patients with celiac disease. (Funded by Dr. Falk Pharma; CEC-3 EudraCT number, 2017-002241-30.).

Randomised clinical trial: faecal microbiota transplantation versus autologous placebo administered via colonoscopy in irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) has been associated with microbial dysbiosis. AIM: To investigate the efficacy of faecal microbiota transplantation (FMT) in the treatment of IBS. METHODS: Forty-nine IBS patients were randomised to receive autologous or allogenic FMT via colonoscopy. The primary endpoint was a sustained, minimum of 50-point, reduction in the IBS Symptom Severity Score. The secondary outcomes were levels of anxiety and depression, changes in quality of life, gut microbiota and faecal water content as assessed with validated questionnaires, intestinal microbiota composition and stool dry weight. RESULTS: The primary endpoint was not achieved in either group. However, there was a transient reduction in the mean IBS Symptom Severity Score in the FMT group at 12 weeks after treatment as compared to baseline (P = 0.01). The groups did not differ in the number of patients achieving clinical response at 12 weeks. In the FMT-treated patients, microbial composition had changed to resemble that of the donor and the stool water content decreased significantly compared to baseline. The depression score decreased in patients with a reduction in IBS symptoms after FMT, but not in those placebo-treated patients who experienced a reduction in IBS symptoms. CONCLUSIONS: FMT provided only a transient relief of symptoms, although it induced a sustained alteration in the microbiota of IBS patients. Therefore, FMT delivered by a single infusion via colonoscopy cannot be recommended as a treatment for IBS in clinical practice. ClinicalTrials.Org, Trial registration number: NCT03561519.

Randomised clinical trial: effect of low-FODMAP rye bread versus regular rye bread on the intestinal microbiota of irritable bowel syndrome patients: association with individual symptom variation.

BACKGROUND: A low intake of Fermentable, Oligo-, Di-, Mono-saccharides and Polyols (FODMAPs) is effective in the symptom control of irritable bowel syndrome (IBS) patients but may exert negative effects on the intestinal microbiota. The microbial effects of increasing regular or non-FODMAP fibre sources are largely unknown. Furthermore, it is not known if the baseline microbiota composition is associated with individual symptom control during the consumption of different rye products in IBS patients. Our objective was to evaluate whether increased consumption of low-FODMAP rye bread or regular rye bread for 4 weeks would alter the intestinal microbiota composition of IBS patients following their habitual diet, and whether these changes associate to symptoms and/or the baseline microbiota. METHODS: The study was conducted as a randomized double blind controlled cross-over study (n = 50). Microbiota was analysed by 16S rRNA gene sequencing and associated with gastrointestinal symptoms. Both microbial changes and their associations to symptoms were secondary outcomes. RESULTS: The consumption of the test breads did not alter microbiota diversity. Compared to baseline, consumption of the low FODMAP rye bread decreased the abundance of Bacteroides, Flavonifractor, Holdemania, Parasutterella and Klebsiella and showed a trend towards increased bifidobacteria, whereas the regular rye bread decreased the abundance of Flavonifractor. When comparing between the two test breads, Klebsiella was decreased after low-FODMAP rye bread intake. Patients whose symptoms decreased during the low-FODMAP rye bread displayed more Blautia and less Barnesiella at baseline. CONCLUSIONS: Consumption of low-FODMAP rye bread had modest, potentially beneficial effects on patients' microbiota while increasing their intake of fibre substantially. The baseline microbiota composition was associated with the variable degrees of symptom relief experienced by the patients. Consumption of a low-FODMAP rye bread might be one way to increase dietary fibre intake and improve the mild dysbiosis often observed among patients with IBS. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02161120. Retrospectively registered 11 June 2014.

Pilot Study: Comparison of Sourdough Wheat Bread and Yeast-Fermented Wheat Bread in Individuals with Wheat Sensitivity and Irritable Bowel Syndrome.

Many patients suspect wheat as being a major trigger of their irritable bowel syndrome (IBS) symptoms. Our aim was to evaluate whether sourdough wheat bread baked without baking improvers and using a long dough fermentation time (>12 h), would result in lower quantities of alpha-amylase/trypsin inhibitors (ATIs) and Fermentable, Oligo-, Di-, Mono-saccharides and Polyols (FODMAPs), and would be better tolerated than yeast-fermented wheat bread for subjects with IBS who have a poor subjective tolerance to wheat. The study was conducted as a randomised double-blind controlled 7-day study (n = 26). Tetrameric ATI structures were unravelled in both breads vs. baking flour, but the overall reduction in ATIs to their monomeric form was higher in the sourdough bread group. Sourdough bread was also lower in FODMAPs. However, no significant differences in gastrointestinal symptoms and markers of low-grade inflammation were found between the study breads. There were significantly more feelings of tiredness, joint symptoms, and decreased alertness when the participants ate the sourdough bread (p ≤ 0.03), but these results should be interpreted with caution. Our novel finding was that sourdough baking reduces the quantities of both ATIs and FODMAPs found in wheat. Nonetheless, the sourdough bread was not tolerated better than the yeast-fermented bread.

Does oral α-galactosidase relieve irritable bowel symptoms?

OBJECTIVE: Abdominal bloating is reported by a majority of irritable bowel syndrome (IBS) patients. Excess colonic fermentation may cause gaseous symptoms. Several foodstuffs contain oligosaccharides with an α-galactosidic linkage that is resistant to mammalian hydrolases. Assisted hydrolysis by exogenous α-galactosidase enzyme (AG) could offer a way of controlling IBS symptoms by reducing colonic fermentation and gas production. The aim of this study was to assess the effect of AG on symptom severity and quality of life in IBS patients with abdominal bloating or flatulence. METHODS: A total of 125 subjects with IBS received AG or placebo at meals for 12 weeks. IBS-Symptom Severity Score (IBS-SSS) and quality of life (QoL) were assessed at baseline, during the treatment and at 4-week follow-up. RESULTS: AG showed a trend toward a more prominent decrease in IBS-SSS. The responder rate at week 16 was higher for the AG group. No difference was detected in QoL between AG and placebo groups. A total of 25 patients (18 in AG group and 7 in placebo group, p = 0.016) withdrew from the study. Abdominal pain and diarrhea were more often reported as reason for withdrawal in AG group. CONCLUSIONS: We found no evidence to support the use of AG routinely in IBS patients. Improvement of clinical response at 4-week follow-up may suggest a long-term effect of unknown mechanism, but could also be attributed to non-responder drop out. Gastrointestinal (GI) side effects may be a coincidence in this study, but irritation of GI tract by AG administration cannot be excluded.

[Autonomic neuropathy--a problem of the circulatory system and digestive tract]. / Autonominen neuropatia--verenkiertoelimistön ja ruoansulatuskanavan ongelma.

An autonomic disorder of the circulatory system becomes manifest as aberrant heart rate variability and baroreflex sensitivity already years before progressing into symptomatic disease, in which case the condition is no longer curable. Diagnosis is based on tests of autonomic nervous system function. The main thing in the treatment is management of risk factors of cardiovascular diseases in addition to enhanced glucose homeostasis. Autonomic neuropathy may also affect the digestive tract and be accompanied by esophageal motility disorder, gastroparesis, diarrhea, constipation or fecal incontinence. It is essential in the diagnosis to exclude other diseases of the digestive tract.

Fecal calprotectin and S100A12 have low utility in prediction of small bowel Crohn's disease detected by wireless capsule endoscopy.

OBJECTIVE: Data on fecal calprotectin and S100A12 in predicting wireless capsule endoscopy (WCE) findings in suspicion of Crohn's disease (CD) are scarce. Our aim was to study the role of calprotectin and S100A12 in predicting inflammatory lesions of small bowel in patients undergoing WCE. MATERIAL AND METHODS: 84 patients undergoing WCE (77 for suspicion of CD and 7 CD patients for evaluation of disease extent) were prospectively recruited. WCE findings were scored. Patients provided a stool sample for measurements of biomarkers. Patients underwent an esophagogastroduodenoscopy and ileocolonoscopy before WCE. RESULTS: WCE was abnormal in 35 (42%) of 84 patients: 14 patients with CD, 8 with NSAID enteropathies, 8 with angioectasias, 4 with polyps or tumors, and 1 with ischemic stricture. Median calprotectin concentration in the study population was 22 µg/g (range 2-342) and S100A12 concentration 0.048 µg/g (range 0.003-1.215). Fecal calprotectin was significantly higher in CD patients (median 91, range 2-312) compared with those with normal WCE or other abnormalities (p = 0.008), whereas fecal S100A12 (0.087 µg/g, range 0.008-0.896) did not differ between the groups (p = 0.166). In detecting inflammatory small bowel lesions, sensitivity, specificity, positive predictive value, and negative predictive value for fecal calprotectin (cutoff 50 µg/g) were 59%, 71%, 42%, and 83%, and for S100A12 (cutoff 0.06 µg/g) these were 59%, 66%, 38%, and 82%. CONCLUSIONS: In predicting small bowel inflammatory changes, fecal biomarkers calprotectin and S100A12 have moderate specificity, but low sensitivity. Neither fecal calprotectin nor S100A12 can be used for screening or excluding small bowel CD.

Capsule endoscopy in pediatric patients: technique and results in our first 100 consecutive children.

OBJECTIVE: Capsule endoscopy (CE) offers noninvasive methods to assess small bowel pathology but only limited data are available on the feasibility, safety, and findings in children. In this study, we report our results of 100 consecutive CE in children. MATERIAL AND METHODS: Single center retrospective study. All pediatric patients (mean age 119 months, range from 8 to 188 months) undergoing CE were included until 100 investigations were completed. The indications for CE were: suspicion or evaluation of Crohn's disease (n = 35) or ulcerative colitis (n = 24), gastrointestinal bleeding (n = 18), and miscellaneous (n = 23). RESULTS: The youngest patients able to swallow the capsule were 84 months old. When the patient was unable to swallow the capsule (n = 51), it was guided into the duodenum with endoscope. In two patients, the capsule remained in the stomach during the 8 h of recording and in 23 cases the capsule failed to reach the cecum. The capsule was expelled naturally in all except one patient. In 39% of the patients, CE revealed a significant finding (multiple ulcers, bleeding, tumors, strictures). In patients examined for bleeding or for a suspicion of Crohn's disease, the respective proportions were 50% and 60%. CONCLUSIONS: This study shows that CE is a feasible diagnostic method to study the small intestine in pediatric patients and that CE can be done in children as young as 8 months old. The diagnostic yield is highest in cases with bleeding or a high suspicion of Crohn's disease.

Nizatidine and gastric emptying in functional dyspepsia.

In clinical practice, H2-receptor antagonists, including nizatidine, in addition to their use in the treatment of peptic ulcer and gastroesophageal reflux, are also useful in alleviating dyspeptic symptoms. Patients with functional dyspepsia show a tendency to delayed gastric emptying. Results of preliminary studies have demonstrated that nizatidine has a prokinetic effect due to its cholinergic properties. The aim of this study was to evaluate the effect of nizatidine on gastric emptying in patients with functional dyspepsia. Sixteen patients with dyspeptic symptoms referred for gastroscopy by primary care physicians were enrolled in this randomized, placebo-controlled, double-blind cross-over study. They received nizatidine 150 mg twice daily or placebo for 2 months. After a 1-month washout period, the 2-month treatment was repeated, with these patients acting as their own controls. Gastric emptying was measured by scintigraphy, and dyspeptic symptoms and quality of life were evaluated at the end of both treatment periods. Gastric emptying of solids during nizatidine therapy was prolonged (T1/2 110.1 +/- 76.7 vs. 65.6 +/- 23.2 min, P = 0.03), but nizatidine had no effect on gastric emptying of liquids. Nizatidine improved the symptom scores and seven of eight aspects of quality of life - but not significantly. In conclusion, nizatidine decreases the gastric emptying rate of solids without having a significant effect on symptoms or quality of life in functional dyspepsia.

Measuring gastric emptying: comparison of 13C-octanoic acid breath test and scintigraphy.

The aim of this study was to compare scintigraphy, the standard method, and the (13)C-octanoic acid breath test (OBT) for measuring gastric emptying. Patients with functional dyspepsia (N = 21, 8 men and 13 women; ages, 40-75) underwent standardized dynamic scintigraphy and OBT. Scintigraphic images were obtained for 90 min and breath samples for 4 hr. The gastric half-emptying time for solids (T(1/2)) was calculated by two previously described mathematical models for the OBT samples: the nonlinear least-squares method and the geometrical method. T(1/2) was significantly longer measured by OBT than by scintigraphy (167 +/- 50 min for the nonlinear least-squares method (P < 0.05) and 185+/- 52 min for the geometrical method (P < 0.005) vs. 109 +/- 74 min for scintigraphy). No correlation appeared between T(1/2) measured by scintigraphy and T(1/2) measured by OBT (r = 0.26) for nonlinear least-squares method and (r = -0.13) for geometrical method). Furthermore, the correlation between the two mathematical models appeared to be low (r = 0.15). Although OBT is simple and safe, its correlation with scintigraphy appears to be weak. The usefulness of this test for measuring gastric emptying thus requires further validation.