E. Miceli

Methodology and indications of H2-breath testing in gastrointestinal diseases: the Rome Consensus Conference

BACKGROUND Breath tests represent a valid and non-invasive diagnostic tool in many gastroenterological conditions. The rationale of hydrogen-breath tests is based on the concept that part of the gas produced by colonic bacterial fermentation diffuses into the blood and is excreted by breath, where it can be quantified easily. There are many differences in the methodology, and the tests are increasingly popular. AIM The Rome Consensus Conference was convened to offer recommendations for clinical practice about the indications and methods of H2-breath testing in gastrointestinal diseases. METHODS Experts were selected on the basis of a proven knowledge/expertise in H2-breath testing and divided into Working Groups (methodology; sugar malabsorption; small intestine bacterial overgrowth; oro-coecal transit time and other gas-related syndromes). They performed a systematic review of the literature, and then formulated statements on the basis of the scientific evidence, which were debated and voted by a multidisciplinary Jury. Recommendations were then modified on the basis of the decisions of the Jury by the members of the Expert Group. RESULTS AND CONCLUSIONS The final statements, graded according to the level of evidence and strength of recommendation, are presented in this document; they identify the indications for the use of H2-breath testing in the clinical practice and methods to be used for performing the tests.

Absorbable vs. non‐absorbable antibiotics in the treatment of small intestine bacterial overgrowth in patients with blind‐loop syndrome

Background : Small intestine bacterial overgrowth is associated with the presence of predisposing conditions, acting through different mechanisms. Therefore, the failure to define a standardized therapy may be due to a methodological bias: to treat a condition characterized by different pathophysiological mechanisms with the same pharmacological approach. Non‐absorbable antibiotics could have a lower efficacy than absorbable drugs in patients with blind loops which exclude a portion of the intestine from the transit.

Meal induced rectosigmoid tone modification: a low caloric meal accurately separates functional and organic gastrointestinal disease patients

Background and aims: Diagnosis of irritable bowel syndrome (IBS) is based on arbitrary criteria due to the lack of an accurate diagnostic test. The aim of this study was to evaluate whether rectosigmoid tone modification after a meal represents an accurate diagnostic approach. Methods: In a secondary care setting, 32 constipation predominant and 24 diarrhoea predominant IBS patients, 10 functional diarrhoea and 10 functional constipation patients, 29 organic gastrointestinal disease patients, and 10 healthy volunteers underwent a rectal barostat test to measure fasting and postprandial rectosigmoid tone. Rectosigmoid response was assessed following three meals containing different amounts of calories: 200 kcal, 400 kcal and 1000 kcal. Results: After 200 kcal, healthy volunteers and patients with organic diseases showed a reduction in rectosigmoid volume of at least 28% of fasting volume, indicating a meal induced increase in muscle tone. In contrast, patients with diarrhoea predominant IBS showed dilation of the rectosigmoid colon, indicative of reduced tone, and patients with constipation predominant IBS showed a mild volume reduction or no modification. Functional diarrhoea and constipation patients showed rectosigmoid tone modification resembling that of the corresponding IBS subtype. A 400 kcal meal normalised rectosigmoid tone in more than half of the constipation predominant IBS patients but none of the diarrhoea predominant IBS patients. In contrast, a 1000 kcal meal normalised tone response in all IBS patients. Sensitivity of the test was 100%, specificity 93%, positive predictive value 96%, and negative predictive value 100%. Conclusion: A postprandial reduction in rectosigmoid tone of at least 28% of fasting value after a low caloric meal accurately separates organic and functional gastrointestinal disease patients. This parameter may therefore be used in the positive diagnosis of IBS.

Visceral hypersensitivity and intolerance symptoms in lactose malabsorption

Abstract  Lactose malabsorption is not always associated with intolerance symptoms. The factors responsible for symptom onset are not yet completely known. As differences in visceral sensitivity may play a role in the pathogenesis of functional symptoms, we evaluated whether an alteration of visceral sensitivity is present in subjects with lactose intolerance. Thirty subjects, recruited regardless of whether they were aware of their capacity to absorb lactose, underwent an evaluation of intestinal hydrogen production capacity by lactulose breath test, followed by an evaluation of lactose absorption by hydrogen breath test after lactose administration and subsequently an evaluation of recto‐sigmoid sensitivity threshold during fasting and after lactulose administration, to ascertain whether fermentation modifies intestinal sensitivity. The role of differences in gastrointestinal transit was excluded by gastric emptying and mouth‐to‐caecum transit time by 13C‐octanoic and lactulose breath tests. Lactulose administration induced a significant reduction of discomfort threshold in subjects with lactose intolerance but not in malabsorbers without intolerance symptoms or in subjects with normal lactose absorption. Perception threshold showed no changes after lactulose administration. Severity of symptoms in intolerant subjects was significantly correlated with the reduction of discomfort thresholds. Visceral hypersensitivity should be considered in the induction of intolerance symptoms in subjects with lactose malabsorption.

Common Features of Patients With Autoimmune Atrophic Gastritis

BACKGROUND & AIMS Autoimmune atrophic gastritis (AIG) is characterized by immune-mediated chronic inflammation of the gastric body and fundus, leading to hypo-achlorhydria and vitamin B12 deficiency. We analyzed the clinical features of AIG and sought to identify factors that might be used in diagnosis. METHODS We collected and analyzed clinical data from 99 consecutive patients (age, 59 ± 17 y) who were diagnosed with AIG, based on histologic factors and the presence of autoantibodies against gastric parietal cells. RESULTS Clinical factors that led to a diagnosis of AIG included hematologic findings related to vitamin B12 deficiency (n = 37), incidental histologic evidence in gastric biopsy specimens (n = 34), immune disorders (n = 18; 9 were celiac disease), neurologic symptoms (n = 6), and a family history of AIG (n = 4). CONCLUSIONS Based on an analysis of 99 consecutive patients with AIG, this disorder is not solely a condition of the elderly. Other features to look for in making a diagnosis of AIG include vitamin B12 deficiency, histologic factors, and immune disorders.

Solute transporters and aquaporins are impaired in celiac disease

Background information. Celiac disease is a chronic inflammatory disorder of the small bowel induced in genetically susceptible subjects by gluten ingestion. Diarrhoea, weight loss and malabsorption represent the major clinical presentation of the disease. Here we examined the possible alteration in the expression and localization of water channels [AQPs (aquaporins)] and some solute transporters in duodenal mucosa of celiac disease patients. Duodenal biopsies from untreated celiacs, treated celiacs, healthy controls and disease controls were considered in the present study. The expressions of some AQPs and transporter mRNAs in human duodenal biopsies were determined by semi‐quantitative RT—PCR (reverse transcription PCR) and real‐time RT—PCR. The localization of AQPs 3, 7 and 10 and of SGLT1 (Na+/glucose co‐transporter 1), PEPT1 (H+/oligopeptide transporter 1) and NHE3 (Na+/H+ exchanger 3) was evaluated by immunohistochemistry.

Fasting and Postprandial Gastric Sensorimotor Activity in Functional Dyspepsia: Postprandial Distress Vs. Epigastric Pain Syndrome

OBJECTIVES:Little information is available on the mechanisms responsible for dyspeptic symptoms in postprandial distress syndrome (PDS), characterized by the presence of prevalently meal-related early satiation and fullness, and the epigastric pain syndrome (EPS), characterized by the prominent symptom of epigastric pain, generally not meal related. In a group of PDS patients, the presence of hypersensitivity to gastric distension in both fasting and postprandial phases was described as the main pathophysiological mechanism; on the contrary, we have no information on the pathophysiology of EPS.METHODS:Sixty Helicobacter pylori (HP)-negative, irritable bowel syndrome (IBS)-negative, and gastroesophageal reflux disease (GERD)-negative patients with functional dyspepsia according to Rome III criteria underwent symptom, anxiety, depression, and somatization evaluation, gastric barostat test, and gastric emptying time evaluation for solids. Fifteen age- and sex-matched healthy volunteers (HVs) were also enrolled as a control group.RESULTS:In PDS patients, the prevalence of both fasting and postprandial hypersensitivity was higher than in EPS patients, and the extent of postprandial reduction of discomfort threshold was significantly correlated with symptom severity. In EPS patients, gastric volume at fasting discomfort threshold and fasting compliance were significantly lower than in PDS patients. Gastric emptying time and gastric accommodation were similar between the two dyspeptic groups. Dyspeptic patients showed a higher prevalence of psychiatric disorders than HVs, but the prevalence was similar between PDS and EPS patients.CONCLUSIONS:Fasting and postprandial hypersensitivity characterize PDS patients and a reduction of gastric compliance is present in EPS patients. However, the pathophysiology of EPS appears more complex than PDS and further studies are needed to analyze central processing and integration of afferent pathways in order to clarify the role of the central nervous system in this condition.

Mixing of the intestinal content and variations of fermentation capacity do not affect the results of hydrogen breath test.

OBJECTIVES:Although the hydrogen (H2) breath test has been in use for many years for diagnosis of sugar malabsorption, research is still underway to improve its diagnostic accuracy. In this study, we investigated whether possible confusing factors caused by the ingestion of the test solution itself (such as the delivery to the colon of other fermentable substrates pre-existing in the small bowel lumen, the release of preformed H2 trapped in the feces, or differences in the fermenting capacity of the colonic bacteria) may interfere with the increase of breath H2 concentration, an expression of malabsorption of the test substrate.METHODS:In 25 patients with untreated celiac disease and 23 sex- and age-matched healthy volunteers, breath H2 excretion was measured after ingestion of a 250-ml solution containing sorbitol, a poorly absorbed alcohol sugar. On 2 other separate days, 12 randomly selected subjects in each group underwent breath H2 excretion measurement after ingestion of 250 ml of a sugar free, nonabsorbable electrolyte solution and 250 ml of a solution containing lactulose, a nonabsorbable disaccharide.RESULTS:After sorbitol ingestion, celiac disease patients showed a significantly higher breath H2 excretion than did healthy volunteers. Otherwise, breath H2 responses to electrolyte solution and lactulose showed no difference between the two groups of subjects.CONCLUSIONS:In a group of patients with sugar malabsorption, increased breath H2 excretion does reflect malabsorption. The washout or the mixing of the intestinal content or intergroup difference of fermenting activity of the colonic bacteria do not represent interfering factors and do not modify the accuracy of the H2 breath test in day-to-day clinical practice.

Breath Methane Excretion Is not An Accurate Marker of Colonic Methane Production in Irritable Bowel Syndrome

OBJECTIVES:The role of colonic methane production in functional bowel disorders is still uncertain. In small samples of irritable bowel syndrome (IBS) patients, it was shown that methane breath excretion correlates with clinical presentation and delayed gastrointestinal transit time. The aim of this study was to evaluate the relationship between intestinal production and breath excretion of CH4 and to correlate CH4 production with the presence and the severity of symptoms, in a large cohort of IBS patients and in a group of healthy volunteers.METHODS:A group of 103 IBS patients and a group of 28 healthy volunteers were enrolled. The presence and severity of symptoms and gastrointestinal transit were evaluated in all subjects, who underwent breath H2/CH4 measurement for 7 h after lactulose to identify breath excretors of these gases; H2 and CH4 were also measured in rectal samples to identify colonic producers. Cumulative H2 and CH4 excretion and production were evaluated by the area under the time–concentration curve calculation (AUC).RESULTS:In IBS patients, CH4 was detected in rectal samples in 48 patients (47%), but only 27 of them (26% of the 103 enrolled patients) excreted this gas with breath. In CH4 producers, the prevalence and severity of symptoms and gastrointestinal transit time were not significantly different with respect to non-producers. IBS subtypes were homogeneously represented in CH4 producers and in non-producers. Healthy volunteers, compared with IBS patients, showed a significantly lower prevalence of CH4 excretion, whereas no difference was found in the prevalence of colonic CH4 production; moreover, in healthy volunteers compared with IBS, CH4 breath excretion and CH4 production were not different in quantitative terms.CONCLUSION:Our data show that colonic CH4 production is not associated with clinical presentation in IBS patients and does not correlate with symptom severity or with gastrointestinal transit time. Clinical inferences based on breath CH4 excretion should undergo an in-depth revision, as this method is not a good marker of CH4 colonic production.

Distribution, Proliferation, and Function of Paneth Cells in Uncomplicated and Complicated Adult Celiac Disease

Paneth cells, granulated epithelial cells located at the base of small bowel crypts, have a crucial role in innate immunity. Because controversies remain concerning Paneth cell numbers and function in celiac disease (CD), we quantified Paneth cells and human alpha-defensin (HD)-5 and HD-6 in 28 patients with uncomplicated CD, 8 patients with complicated CD (3 with ulcerative jejunoileitis, 2 with refractory sprue, and 3 with enteropathy-associated T-cell lymphoma), and 14 control subjects. Paneth cell numbers and proliferation did not differ in uncomplicated untreated and treated CD and control cases. However, the number of Paneth cells was significantly reduced in complicated CD. Mucosal HD-5 and HD-6 were comparable in uncomplicated untreated and treated CD and control cases. Ex vivo gliadin challenge of treated CD biopsy specimens had no effect on mucosal HD-5 and HD-6 transcripts. Paneth cell numbers and alpha-defensins are unchanged in the mucosa in uncomplicated CD. Further studies are needed to clarify the implications of reduction of numbers of Paneth cells in complicated CD.