Unsupervised Learning for Hydrogen Breath Tests

Hydrogen breath tests are a well-established method to help diagnose functional intestinal disorders such as carbohydrate malabsorption or small intestinal bacterial overgrowth. In this work we apply unsupervised machine learning techniques to analyze hydrogen breath test datasets. We propose a method that uses 26 internal cluster validation measures to determine a suitable number of clusters. In an induced external validation step we use a predefined categorization proposed by a medical expert. The results indicate that the majority of the considered internal validation indexes was not able to produce a reasonable clustering. Considering a predefined categorization performed by a medical expert, a novel shape-based method obtained the highest external validation measure in terms of adjusted rand index. The predefined clusterings constitute the basis of a supervised machine learning step that is part of our ongoing research.

Hydrogen Breath Tests: Are They Really Useful in the Nutritional Management of Digestive Disease?

Background: Carbohydrate malabsorption is a frequent digestive problem associated with abdominal pain, bloating and diarrhea. Hydrogen breath testing (BT) represents the most reliable and validated diagnostic technique. The aim of this manuscript was to clarify the usefulness of BTs in the nutritional management of these disorders. Methods: A literature search for BT related to carbohydrate malabsorption was carried out using the online databases of Pubmed, Medline and Cochrane. Results: Lactose BT showed good sensitivity and optimal specificity for lactose malabsorption. However, an accurate diagnosis of lactose intolerance should require blind lactose challenge although this method is difficult to utilize in clinical practice. Regarding dose-depending fructose and sorbitol malabsorption, BTs could not add diagnostic advantage compared with a direct dietary intervention. In addition, carbohydrates are fundamental components of fermentable oligo-, di- and monosaccharides and polyols (FODMAPs). Before starting a low FODMAP diet, lactose BT should be suggested in a population with low prevalence of hypolactasia. Conclusions: BTs represent a valid and noninvasive technique in many digestive conditions. Regarding the management of carbohydrate intolerance, lactose BT can be recommended with some limitations. No sufficient evidence is available about the usefulness of BTs for other sugars in clinical practice.

MODERN RESOURCES OF CELIAC DISEASE TREATMENT EFFECTIVENESS IMPROVEMENT

Relevance. Although monotherapy with a gluten-free diet (BGD) for celiac disease is highly effective, it does not in all cases achieve complete remission of the disease. Therefore, an additional comprehensive examination of patients for the purpose of prescribing reasonable therapy is relevant. Objective: to study the causes of the persistence of clinical symptoms in patients with celiac disease who are on a gluten-free diet for 6 months. Materials and methods. Patients with celiac disease (n = 41) who were on a gluten-free diet (GFD) for 6 months were studied. The average age is 35.42 ± 0.45 years. Group 1 (n = 17) – patients who subjectively noted a positive dynamics of treatment and with a significant improvement in general condition, but without complete clinical remission. Group 2 (n = 24) – patients with unsatisfactory treatment results, no clinical effect from treatment, or weak positive dynamics on the background of GFD. The study included two stages: 1) assessment of patients' compliance and their diet (through the analysis of food diaries) in order to identify disorders of a gluten-free diet as the main cause of the persistence of clinical symptoms; 2) identification of other causes of the persistence of symptoms: exocrine pancreas insufficiency (EPI), lactase deficiency (LD) and the syndrome of increase bacterial growth (SIBR). A C13 triglyceride breath test (IRIS analyzer) was performed to diagnose EPI. To diagnose LD and SIBR in the small intestine, hydrogen breath tests (Micro H2-meter analyzer) were used – a test with lactose and D-xylose, respectively. Also, the titer of antibodies to tissue transglutaminase (TTG) to deaminated gliadin peptides (DPG) was determined in all patients, and their DPG/TTG ratio was calculated. Results. The main reason for the ineffectiveness of treatment is a violation of a gluten-free diet, found in 63.4% of subjects (incompletely formed mushy stool, polyfaeces, steatorrhea; recurrent abdominal pain, bloating, flatulence). Revision of food intake and elimination of sources of latent gluten from the diet of patients with celiac disease allowed to achieve complete serological remission (normalization of titers specific for celiac disease antibodies) in all patients, but complete clinical remission was achieved in only 34.6%. Therefore, it is concluded that there are other causes of incomplete remission of celiac disease associated with concomitant diseases of the digestive tract. Using carbon and hydrogen breath tests, it was found that, in addition to diet, the reasons for the lack of complete remission in patients with celiac disease are EPI (19%), SIBR in the small intestine (16%), LD (47%) and a combination of EPI with SIBR. Conclusion. The inclusion of respiratory tests (C13-triglyceride, hydrogen with lactose, and D-xylose) in a comprehensive examination of patients with celiac disease can significantly improve treatment outcomes and reduce the duration of clinical remission.

Roles of Lactose and Fructose Malabsorption and Dietary Outcomes in Children Presenting with Chronic Abdominal Pain

Intolerance to lactose or fructose is frequently diagnosed in children with chronic abdominal pain (CAP). However, the causal relationship remains a matter of discussion. A cohort of 253 patients, aged 7–12 years, presenting with unexplained CAP received standardized diagnostics. Additional diagnostic tests were performed based on their medical history and physical and laboratory investigations. Fructose and lactose hydrogen breath tests (H2BT) as well as empiric diagnostic elimination diets were performed in 135 patients reporting abdominal pain related to the consumption of lactose or fructose to evaluate carbohydrate intolerance as a potential cause of CAP. Carbohydrate malabsorption by H2BT was found in 55 (41%) out of 135 patients. An abnormal increase in H2BT was revealed in 30% (35/118) of patients after fructose consumption and in 18% (20/114) of patients after lactose administration. Forty-six percent (25/54) reported pain relief during a diagnostic elimination diet. In total, 17 patients had lactose malabsorption, 29 fructose malabsorption, and nine combined carbohydrate malabsorption. Carbohydrate intolerance as a cause of CAP was diagnosed at follow-up in only 18% (10/55) of patients with malabsorption after the elimination of the respective carbohydrate. Thus, carbohydrate malabsorption appears to be an incidental finding in children with functional abdominal pain disorders, rather than its cause. Therefore, testing of carbohydrate intolerance should only be considered in children with a strong clinical suspicion and with the goal to prevent long-term unnecessary dietary restrictions in children suffering from CAP.

Rational investigations in irritable bowel syndrome

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder which accounts for a substantial proportion of a gastroenterologist’s time in the outpatient clinic. However, there is variability in approaches to diagnosis and investigation between physicians, dependent on expertise. Many patients express disappointment over the lack of a patient-centred approach. Consequently, there have been calls for the care of patients with IBS to be standardised, a process which aims to promote high-quality and high-value care. Making an early diagnosis, based on a clinical assessment of symptoms, while limiting use of investigations, are key tenets of this process. Exhaustive investigation to exclude all organic pathology is unnecessary, and may be counterproductive. Routine blood tests in suspected IBS have low yield, but are an acceptable part of routine practice. All patients should have coeliac serology tested, regardless of their predominant stool form. Patients with diarrhoea should have a faecal calprotectin measured, and should proceed to colonoscopy to exclude inflammatory bowel disease (IBD) if this is positive. Beyond this, the need for investigations should be made on a case-by-case basis, contingent on the reporting of known risk factors for organic pathology. Colonoscopy should be considered in any patient with alarm features for colorectal cancer, and in those whose clinical features are suggestive of microscopic colitis. A 23-seleno-25-homotaurocholic acid (SeHCAT) scan should be considered in patients with IBS-D, a third of whom may actually have bile acid diarrhoea. There is no role for routine hydrogen breath tests for lactose malabsorption or small intestinal bacterial overgrowth.

3185 A Randomized Controlled Trial Comparing the Nonabsorbable Antibiotic Rifaximin vs. Dietary Intervention Low in Fermentable Sugars (FODMAP) in Irritable Bowel Syndrome

OBJECTIVES/SPECIFIC AIMS: Objectives and goals of this study are to (i) determine whether IBS-D patients randomized to either rifaximin or low FODMAP diet show improvement in IBS-related symptoms; and (2) identify using longitudinal analyses how SIBO status and fecal microbiota features associate with response to either rifaximin or low FODMAP dietary intervention. METHODS/STUDY POPULATION: 42 patients ≥ 18 years of age who meet Rome IV criteria for IBS-D will be randomized to receive either rifaximin or low FODMAP diet intervention. The primary outcome will be the proportion of responders to intervention which is defined as ≥ 30% reduction in mean daily abdominal pain or bloating by visual analog scale compared with baseline. Exclusion criteria will include: (a) history of microscopic colitis, inflammatory bowel disease, celiac disease, or other organic disease that could explain symptoms, (b) prior gastrointestinal surgery, other than appendectomy or cholecystectomy > 6 months prior to study initiation, (c) prior use of rifaximin or formal dietary interventions for IBS-D, (d) use of antibiotics within the past 3 months, or (e) use of probiotics within 1 month of study entry. Glucose hydrogen breath tests will be performed at the beginning and end of the trial to evaluate for SIBO. Fecal samples will be collected at 0, 2, and 6 weeks to determine changes in fecal microbial composition and structure. RESULTS/ANTICIPATED RESULTS: This study seeks to examine whether longitudinal analyses of small intestinal and colonic microbiota can subtype IBS-D subjects into clinically relevant phenotypes. A total of 18 subjects have been enrolled into the study. Clinical variables, hydrogen breath test results, and fecal microbiota data are being collected for ongoing analysis. DISCUSSION/SIGNIFICANCE OF IMPACT: Results from this study may help move treatment of IBS from a purely symptom based approach to a more individualized approach by stratifying IBS-D patients into distinct clinical phenotypes which are amenable to targeted therapeutic approaches.

The oral cavity micro-biocenosis in case of desquamative glossitis associated with small intestinal bacterial overgrowth

Relevance of the research topic. Small intestine bacterial overgrowth (SIBO) is one of the major factors in the development and persistence of digestive diseases and associated non-digestive disorders. The human gastrointestinal tract microbiota of different biotypes features a community of microorganisms with complex interrelationships. The mouth is the beginning of the digestive system and most easily accessible organ for specimen collection. Assessment of the oral mucosal surface works as a diagnostic test reflecting a somatic pathogenesis at its earliest stages. A hydrogen breath test is a non-invasive diagnostic tool for SIBO. The test entails measuring the hydrogen concentration in the exhaled air which is the metabolite of a quantitatively and qualitatively changed intestinal microflora. Small intestinal microbiota imbalance triggers the impairment of other gastrointestinal tract organs. It can cause oral, upper respiratory and gut tract microbial dysbiosis.Purpose. The main concern of this study is to explore the oral microbiota of patients with desquamative glossitis coupled with SIBO.Methods and materials. Clinical studies of 36 patients with desquamative glossitis and varying degrees of severity of SIBO generated data for this research. The comparison group comprised 12 persons with desquamative glossitis not paired by SIBO. The generated data was juxtaposed to normal reference values of the oral microbiota biocenosis. SIBO was diagnosed through hydrogen breath monitoring provided by the Gastro+Gastroliyser (BEDFONT) system while oral microflora was assessed based on culture tests.Results. The research showed that patients with more severe SIBO and desquamative glossitis manifest a more apparent oral dysbiosis with a simultaneous decrease of normal bacteria and an increase in the amount of conditionally pathogenic bacteria. However, patients who have desquamative glossitis but do not suffer from SIBO tend to show a stable normal microbial flora and a growth of conditionally pathogenic bacteria.Summary. The research revealed that the deranged oral microbiota of patients with desquamative glossitis vary in its degree depending on the severity of SIBO as shown by hydrogen breath tests.

A correction of a gut microflora composition for the allergic bronchial asthma complex therapy

The efficacy of a gut microbiota control was investigated for patients with atopic asthma. 45 patients with atopic asthma were included in the study. The results of our clinical and lab tests, pulmonary function tests and the lactulose hydrogen breath tests have been presented to evaluate small intestine bacterial overgrowth (SIBO). Under the standard SIBO’s therapy (long-acting beta-agonists, inhaled glucocorticoids), the first group (15 patients) had being tested with Rifaximin for the SIBO therapy during 7 days. The second group (15 patients) had been tested with Rifaximin and with a succeeding probiotics therapy for three months (B. bifidum, B. longum, B. infantis, L. rhamnosus). SIBO was diagnosed for 30 (67%) patients. We have detected a higher IgE level (P<0.01), a higher eosinophils level (P<0.001) in sputum and more significant decrease of FEV1 (P<0.01) in SIBO(+). The IgE level in patients was decreased (P<0.01) after the complex SIBO therapy both for the Rifaximin therapy group (P<0.05) and for the Rifaximin + Probiotic therapy group (P<0.05). A dramatic decrease of the IgE level (P<0.05) had been induced by probiotics and it was confirmed by the control testing results with a high statistical accuracy for the observed groups of patients. We did not detect any changes for the patients without SIBO (P=0.46), those who had been treated with a standard therapy. A decrease in the number of patient hospitalization was defined by the treatment with probiotics after SIBO therapy (P<0.05). So, SIBO is a significant factor aggravating the atopic asthma in patients. The gut microflora correction with probiotics therapy has been accompanied by a statistical reliability improvement for the immune response and spirometry, as well as by a decrease in the number of hospitalizations for these patients during the year.