Role of exhaled hydrogen sulfide in the diagnosis of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is often accompanied by increased excretion of hydrogen sulfide (H2S). This study aimed to explore the value of exhaled H2S in the diagnosis of CRC. METHODS: A total of 80 people with normal colonoscopy results and 57 patients with CRC were enrolled into the present observational cohort study. Exhaled oral and nasal H2S were detected by Nanocoulomb breath analyser. Results were compared between the two groups. Receiver operating characteristic (ROC) curves were analysed and area under the curves (AUCs) were calculated to assess the diagnostic value of exhaled H2S. Meanwhile, the clinicopathological features, including gender, lesion location and tumour staging of patients with CRC, were also collected and analysed. RESULTS: The amount of exhaled H2S from patients with CRC was significantly higher than that of those with normal colonoscopy results. The ROC curve showed an AUC value of 0.73 and 0.71 based on oral and nasal H2S detection, respectively. The exhaled H2S in patients with CRC was correlated with gender, lesion location and tumour progression, including depth of invasion, lymphatic metastasis and TNM (Tumor, Lymph Nodes, Metastasis) staging. CONCLUSION: Exhaled H2S analysis is a convenient and non-invasive detection method for diagnosing CRC, suggesting a potential role in population screening for CRC.

Characteristics of oxygen concentration and the role of correction factor in real-time GI breath test.

OBJECTIVE: A high quality end-expiratory breath sample is required for a reliable gastrointestinal breath test result. Oxygen (O2) concentration in the breath sample can be used as a quality marker. This study investigated the characteristics of O2 concentration in the breath sample and the impact of using a correction factor in real-time breath measurement. DESIGN: This study includes two separate groups of patient data. Part 1 of the study analysed the patient's ability to deliver end-expiratory breath samples over a 2-year period (n=564). Part 2 of the study analysed a separate group of patients (n=47) with additional data to investigate the O2 characteristics and the role of correction factor in breath test. RESULTS: The results indicated 95.4% of 564 patients were able to achieve an O2 concentration below 14% in their end-expiratory breath. Part 2 of the study revealed that the distribution of O2 concentration was between 9.5% and 16.2%. Applying a correction factor to predict the end-expiratory H2 and CH4 values led to an average measurement error of -36.4% and -12.8%, respectively. CONCLUSION: The majority of patients are able to deliver a high quality end-expiratory breath sample, regardless of age or gender. The correction factor algorithm is unreliable when predicting the end-expiratory result at 15% O2 and it would have resulted in false negative result for 50% of the positive cases in this study. It has also indicated that the continuous O2 measurement is essential to ensure breath sample quality by preventing secondary breathing during real-time breath collection.

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.

Update on lactose malabsorption and intolerance: pathogenesis, diagnosis and clinical management.

Lactose is the main source of calories in milk, an essential nutriedigestion, patients with visceral hypersensitivity nt in infancy and a key part of the diet in populations that maintain the ability to digest this disaccharide in adulthood. Lactase deficiency (LD) is the failure to express the enzyme that hydrolyses lactose into galactose and glucose in the small intestine. The genetic mechanism of lactase persistence in adult Caucasians is mediated by a single C→T nucleotide polymorphism at the LCTbo -13'910 locus on chromosome-2. Lactose malabsorption (LM) refers to any cause of failure to digest and/or absorb lactose in the small intestine. This includes primary genetic and also secondary LD due to infection or other conditions that affect the mucosal integrity of the small bowel. Lactose intolerance (LI) is defined as the onset of abdominal symptoms such as abdominal pain, bloating and diarrhoea after lactose ingestion by an individual with LM. The likelihood of LI depends on the lactose dose, lactase expression and the intestinal microbiome. Independent of lactose digestion, patients with visceral hypersensitivity associated with anxiety or the Irritable Bowel Syndrome (IBS) are at increased risk of the condition. Diagnostic investigations available to diagnose LM and LI include genetic, endoscopic and physiological tests. The association between self-reported LI, objective findings and clinical outcome of dietary intervention is variable. Treatment of LI can include low-lactose diet, lactase supplementation and, potentially, colonic adaptation by prebiotics. The clinical outcome of these treatments is modest, because lactose is just one of a number of poorly absorbed carbohydrates which can cause symptoms by similar mechanisms.

The prevalence of small intestinal bacterial overgrowth in non-surgical patients with chronic pancreatitis and pancreatic exocrine insufficiency (PEI).

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is a condition characterised by symptoms similar to pancreatic exocrine insufficiency (PEI) in chronic pancreatitis patients. SIBO is thought to complicate chronic pancreatitis in up to 92% of cases; however, studies are heterogeneous and protocols non-standardised. SIBO may be determined by measuring lung air-expiration of either hydrogen or methane which are by-products of small bowel bacterial fermentation of intraluminal substrates such as carbohydrates. We evaluated the prevalence of SIBO among a defined cohort of non-surgical chronic pancreatitics with mild to severe PEI compared with matched healthy controls. METHODS: Thirty-five patients and 31 age-, gender- and smoking status-matched healthy controls were evaluated for SIBO by means of a fasting glucose hydrogen breath test (GHBT). The relationship between SIBO and clinical symptoms in chronic pancreatitis was evaluated. RESULTS: SIBO was present in 15% of chronic pancreatitis patients, while no healthy controls tested positive (P = 0.029). SIBO was more prevalent in those taking pancreatic enzyme replacement therapy (PERT) (P = 0.016), with proton pump inhibitor use (PPI) (P = 0.022) and in those with alcohol aetiology (P = 0.023). Patients with concurrent diabetes were more often SIBO-positive and this was statistically significant (P = 0.009). There were no statistically significant differences in reported symptoms between patients with and without SIBO, with the exception of 'weight loss', with patients reporting weight loss more likely to have SIBO (P = 0.047). CONCLUSION: The prevalence of SIBO in this study was almost 15% and consistent with other studies of SIBO in non-surgical chronic pancreatitis patients. These data support the testing of patients with clinically-relevant PEI unresolved by adequate doses of PERT, particularly in those patients with concurrent diabetes. SIBO can be easily diagnosed therefore allowing more specific and more targeted symptom treatment.

Low-grade small intestinal bacterial overgrowth is common in patients with non-alcoholic steatohepatitis on quantitative jejunal aspirate culture.

BACKGROUND: Though pathogenesis of non-alcoholic steatohepatitis (NASH) is unclear, association with small intestinal bacterial overgrowth [SIBO] and fecal dysbiosis is suggested. We evaluated SIBO in NASH using quantitative jejunal aspirate culture (conventional criteria: ≥ 105 colony forming unit (CFU)/mL and newer cutoff ≥ 103 CFU/mL) and glucose hydrogen breath test. METHODS: Thirty-eight patients with NASH (age 37.5 years, range 20-54, 9, 24% female), diagnosed by ultrasonography, alanine aminotransferase >1.5 times normal and liver biopsy (in 27/38, 71%) and exclusion of other causes and 12 constipation-predominant irritable bowel syndrome as historical controls (age 39.5-y, 26-44; 3, 25% female) without fatty liver were studied. RESULTS: Jejunal aspirates, obtained in 35/38 patients, were sterile in 14/35 (40%) and bacteria isolated in 21 (60%) (all aerobic, in one anaerobe also; Gram positive 5, negative 13, both 3). In contrast, bacteria (two Gram negative) were isolated in 3/12 (25%) controls (odds ratio 4.5, 95% CI 1.0-19.5; p = 0.04); colony counts were higher in NASH than controls (median 380 CFU/mL, 0-200,000 vs. 0 CFU/mL, 0-1000; p = 0.02). Gram negative bacteria tended to be commoner in NASH than controls (16/35 vs. 2/12; p = 0.07). Seven out of 35 (20%) patients with NASH (≥ 105 CFU/mL in 5 and 2 other on glucose hydrogen breath test) and no control had SIBO (p = ns); low-grade SIBO (≥103 CFU/mL) was commoner in NASH than controls (14/35, 40%, vs. 1/12, 8.3%; p = 0.04). There was no correlation between bacterial colony count and bacterial type and anthropometric and biochemical parameters. CONCLUSION: Low-grade bacterial overgrowth, particularly with Gram negative bacteria, was commoner in NASH than controls.

Prevalence of abnormal lactose breath hydrogen tests in children with functional abdominal pain.

OBJECTIVES: The study was undertaken to determine the prevalence of abnormal lactose breath hydrogen test in children with non-organic chronic abdominal pain. METHODS: Children with chronic abdominal pain were examined and investigated for organic causes. All children without a known organic cause underwent lactose and glucose breath hydrogen test. After a standard dose of 2 g/kg of lactose to a maximum of 50 g, hydrogen in breath was measured at 15 min intervals for 3 h. A rise of 20 ppm above baseline was considered suggestive of lactose malabsorption. RESULTS: Of 108 children screened, organic causes were found in 46 children. Sixty-two patients without any organic cause underwent hydrogen breath test. Lactose hydrogen breath test (HBT) was positive in 36 of 62 (58%), while 11 (17%) had positive HBT with glucose suggestive of small intestinal bacterial overgrowth (SIBO). Twenty out of 34 (59%) improved on lactose free diet while 8 out of 11 (72%) children of SIBO improved on antibiotics. CONCLUSIONS: Lactose malabsorption was seen in 58% of children with non-organic chronic abdominal pain.

Levothyroxine therapy and impaired clearance are the strongest contributors to small intestinal bacterial overgrowth: Results of a retrospective cohort study.

AIM: To identify a set of contributors, and weight and rank them on a pathophysiological basis. METHODS: Patients who have undergone a lactulose or glucose hydrogen breath test to rule out small intestinal bacterial overgrowth (SIBO) for various clinical symptoms, including diarrhoea, weight loss, abdominal pain, cramping or bloating, were seen as eligible for inclusion in a retrospective single-centre study. Clinical data such as co-morbidities, medication, laboratory parameters and other possible risk factors have been identified from the electronic data system. Cases lacking or with substantially incomplete clinical data were excluded from the analysis. Suspected contributors were summarised under four different pathophysiological pathways (impaired gastric acid barrier, impaired intestinal clearance, immunosuppression and miscellaneous factors including thyroid gland variables) and investigated using the χ2 test, Student's t-test and logistic regression models. RESULTS: A total of 1809 patients who had undergone hydrogen breath testing were analysed. Impairment of the gastric acid barrier (gastrectomy, odds ratio: OR = 3.5, PPI therapy OR = 1.4), impairment of intestinal clearance (any resecting gastric surgery OR = 2.6, any colonic resection OR = 1.9, stenosis OR = 3.4, gastroparesis OR = 3.4, neuropathy 2.2), immunological factors (any drug-induced immunosuppression OR = 1.8), altered thyroid gland metabolism (hypothyroidism OR = 2.6, levothyroxine therapy OR = 3.0) and diabetes mellitus (OR = 1.9) were associated significantly to SIBO. Any abdominal surgery, ileocecal resection, vagotomy or IgA-deficiency did not have any influence, and a history of appendectomy decreased the risk of SIBO. Multivariate analysis revealed gastric surgery, stenoses, medical immunosuppression and levothyroxine to be the strongest predictors. Levothyroxine therapy was the strongest contributor in a simplified model (OR = 3.0). CONCLUSION: The most important contributors for the development of SIBO in ascending order are immunosuppression, impairment of intestinal clearance and levothyroxine use, but they do not sufficiently explain its emergence.

Small Intestinal Bacterial Overgrowth and Other Intestinal Disorders.

Gut microbiota is the largest organ of the human body. Although growth of bacteria more than 105 colony forming unit (CFU) per milliliter in culture of upper gut aspirate is used to diagnosis small intestinal bacterial overgrowth (SIBO), 103 CFU or more is being considered to suggest the diagnosis, particularly if colonic type bacteria are present in the upper gut. Although neither very sensitive nor specific, hydrogen breath tests are widely used to diagnose SIBO. Rifaximin is the best treatment for SIBO due to its broad spectrum, lack of systemic absorption, and safety profile.

Hydrogen breath tests in gastrointestinal diseases.

Hydrogen breath tests are widely used to explore pathophysiology of functional gastrointestinal (GI) disorders. Small intestinal bacterial overgrowth (SIBO) and carbohydrate malabsorption are disorders detected by these tests that have been proposed to be of great importance for symptoms of GI diseases. Glucose hydrogen breath test is more acceptable for diagnosis of SIBO whereas lactose and fructose hydrogen breath tests are used for detection of lactose and fructose maldigestion respectively. Lactulose hydrogen breath test is also used widely to measure the orocecal transit time for GI motility. These methods are noninvasive and inexpensive. Many patients with functional gut disorders are unaware of the relationship between diet and GI symptoms they present. In particular, patients with chronic symptoms may regard their condition as normal and may not be aware that their symptoms can be effectively managed following a proper diagnosis. Patients with symptoms of abdominal pain, bloating, flatulence and altered bowel movements (diarrhea and constipation), or with a medical diagnosis of irritable bowel syndrome or celiac disease, may have undiagnosed carbohydrate malabsorption or SIBO. Hydrogen breath tests are specific and sensitive diagnostic tests that can be used to either confirm or eliminate the possibility of carbohydrate malabsorption or SIBO in such patients. Breath tests, though valuable tools, are underutilized in evaluating dyspepsia and functional bloating and diarrhea as well as suspected malabsorption. However, because of their simplicity, reproducibility and safety of procedure they are now being substituted to more uncomfortable and expensive techniques that were traditionally used in gastroenterology.

Dietary sorbitol and mannitol: food content and distinct absorption patterns between healthy individuals and patients with irritable bowel syndrome.

BACKGROUND: Sorbitol and mannitol are naturally-occurring polyol isomers. Although poor absorption and induction of gastrointestinal symptoms by sorbitol are known, the properties of mannitol are poorly described. We aimed to expand data on food composition of these polyols, and to compare their absorptive capacities and symptom induction in patients with irritable bowel syndrome (IBS) and healthy individuals. METHODS: Food samples were analysed for sorbitol and mannitol content. The degree of absorption measured by breath hydrogen production and gastrointestinal symptoms (visual analogue scales) was evaluated in a randomised, double-blinded, placebo-controlled study in 21 healthy and 20 IBS subjects after challenges with 10 g of sorbitol, mannitol or glucose. RESULTS: Certain fruits and sugar-free gum contained sorbitol, whereas mannitol content was higher in certain vegetables. Similar proportions of patients with IBS (40%) and healthy subjects (33%) completely absorbed sorbitol, although more so with IBS absorbed mannitol (80% versus 43%; P = 0.02). Breath hydrogen production was similar in both groups after lactulose but was reduced in patients with IBS after both polyols. No difference in mean (SEM) hydrogen production was found in healthy controls after sorbitol [area-under-the-curve: 2766 (591) ppm 4 h(-1) ] or mannitol [2062 (468) ppm 4 h(-1) ] but, in patients with IBS, this was greater after sorbitol [1136 (204) ppm 4 h(-1) ] than mannitol [404 (154) ppm 4 h(-1) ; P = 0.002]. Overall gastrointestinal symptoms increased significantly after both polyols in patients with IBS only, although they were independent of malabsorption of either of the polyols. CONCLUSIONS: Increased and discordant absorption of mannitol and sorbitol occurs in patients with IBS compared to that in healthy controls. Polyols induced gastrointestinal symptoms in patients with IBS independently of their absorptive patterns, suggesting that the dietary restriction of polyols may be efficacious.