Hydrogen Breath Test Research Articles

The intestinal microbiome, but not clinical aspects of inflammatory bowel disease, is impacted by lactose malabsorption compared to lactose digestion in children

BackgroundDietary exclusion of lactose from patients with inflammatory bowel disease (IBD) persists with speculation that deleterious effects are mediated through intestinal microbes. ObjectivesTo compare IBD characteristics and changes in the intestinal microbiome (IM) at diagnosis in children with and without lactose malabsorption (LM). MethodsA cross-sectional cohort of children (8–17 y of age) diagnosed with Crohn’s disease [n = 149 (63%)] or ulcerative colitis (n = 86) that had undergone lactose breath hydrogen testing was evaluated. The IM of mucosal luminal aspirates was profiled at the time of diagnosis using 16S ribosomal ribonucleic acid gene amplicon sequencing of the V6 hypervariable region. ResultsOf the 235 children, 61 (26%) had LM. Microbial characterization yielded differences in bacterial differential abundance between children who could and could not absorb lactose, which varied by intestinal site and between subtypes of IBD. There were no differences in the ages [13.2 ± 3.0 y (mean ± standard deviation) compared with 12.7 ± 3.4 y; P = 0.25], sex (P = 0.88), extent of disease involvement or severity of disease at presentation (P = 0.74) when comparing those that could or could not absorb lactose nor was there a difference in the need for initiation of biological agents (P = 0.43) during 2 y of follow-up. ConclusionsLM does not affect the clinical presentation or outcomes of children with IBD. However, this study establishes that a single nonabsorbed fermentable food product can alter the IM in both a regional and disease-specific manner. As we continue to learn more about the pathophysiology of IBD and the role of the IM in disease onset and progression, it would be of benefit to examine the impact of other potential fermentable nutrients and their products on IBD outcomes.

Self-Perceived Lactose Intolerance Versus Confirmed Lactose Intolerance in Irritable Bowel Syndrome: A Systematic Review.

Disorders of gut-brain interaction (DGBI) are prevalent, affecting 20-40% of the population, with irritable bowel syndrome (IBS) being the most common and impactful. While congenital lactose intolerance is rare, lactase deficiency in adults is widespread, causing gastrointestinal symptoms like bloating and diarrhea. Self-perceived lactose intolerance often overestimates symptoms, impacting dietary choices and quality of life, necessitating better understanding and management for improved patient outcomes. This article evaluates the diagnostic accuracy of self-reported lactose intolerance in patients with lactose intolerance and IBS through a systematic review. A systematic literature search was conducted using PubMed, EMBASE, and SCOPUS, including terms related to IBS, lactose intolerance, and self-reported symptoms, without applying filters to ensure comprehensive coverage. Inclusion criteria focused on observational studies with adult participants diagnosed with lactose intolerance, addressing symptoms and lactose malabsorption, while excluding non-English articles, reviews, editorials, and studies involving pediatric subjects. The systematic review analyzed six studies with 845 participants, revealing significant variability and moderate accuracy in self-reported lactose intolerance for diagnosing actual lactose intolerance in IBS patients. Hydrogen breath tests (HBTs) showed that self-reported symptoms often led to false positives, underscoring the need for objective diagnostic tools and standardized criteria. The findings highlight the complexity of diagnosing lactose intolerance in IBS patients and suggest that lactose-free diets and routine HBT should not be recommended without clear indications. The rigorous selection process ensured the inclusion of high-quality, relevant studies, thereby enhancing the reliability and validity of the review's findings. These studies revealed that a lactose-free diet should not be routinely recommended for IBS patients, nor should the routine use of HBT to identify lactose malabsorption in this group. Future research should focus on better understanding the factors influencing lactose perception and tolerance, which is crucial for more effective management of lactose intolerance in IBS patients.

Validation of a Hand-Held Point-of-Care Device to Measure Breath Hydrogen and Its Utility in Detecting Response to Antibiotic Treatment.

Breath testing for small intestinal bacterial overgrowth (SIBO) is typically performed using clinic-based equipment or single-use test kits. This study aimed to evaluate the utility of a portable, point-of-care breath analysis device (AIRE®, FoodMarble) in patients suspected to have SIBO. A technical assessment including a comparison to existing mail-in kits was first performed. Then, postprandial breath hydrogen levels of patients before and after antibiotic treatment were gathered and compared to levels seen in a healthy cohort. For the comparison, 50 patients suspected of having SIBO were provided with an AIRE device and performed concurrent LHBTs at-home with a mail-in breath test kit. For the postprandial analysis, twenty-four patients with chronic GI symptoms measured their postprandial hydrogen for 7days prior to antibiotic treatment and for 7days after treatment. 10 healthy controls also measured their postprandial hydrogen for 7days. Substantial agreement was demonstrated between AIRE and the mail-in kits for the performance of lactulose hydrogen breath tests (κ = 0.8). Prior to treatment, patients had significantly greater daily postprandial hydrogen than healthy controls (p < 0.001). The mean postprandial hydrogen of patients reduced significantly after treatment (p < 0.001). Measuring postprandial hydrogen shows potential as a means of differentiating patients with chronic GI symptoms from healthy controls and may be useful in monitoring patients before, during, and after treatment. Future studies could help determine if pre-treatment breath gas levels are predictive of response to antibiotic treatment.

Hydrogen breath test as a diagnostic tool

Introduction and Purpose: Hydrogen breath tests serve the crucial purpose of evaluating the absorption of nutrients in the small intestine, particularly when carbohydrates are not properly absorbed, leading to bacterial overgrowth. These tests are non-invasive, cost-effective, and widely accessible diagnostic tools used to assess various gastrointestinal disorders. The objective of this review is to evaluate the effectiveness and methodology of Hydrogen breath testing (HBT). State of knowledge: The disposal of hydrogen gas is essential for maintaining efficient microbial fermentation processes in the gut. Hydrogenotrophic microbes, including acetogens, methanogenic archaea, and sulfate-reducing bacteria, are responsible for this process. Hydrogen breath tests, conducted with substrates like glucose and lactulose, aid in diagnosing conditions such as small intestinal bacterial overgrowth (SIBO), lactose and fructose intolerance, and other carbohydrate absorption disorders. These tests generate a large volume of data, which can be analyzed using data mining techniques to uncover new hypotheses. Conclusions: Hydrogen breath tests, using various substrates, are effective in diagnosing gastrointestinal disorders such as SIBO and carbohydrate malabsorption. They offer valuable insights into microbial processes in the gut and can inform individualized treatment strategies. However, careful consideration of contraindications and proper test administration protocols is essential for accurate diagnosis and interpretation of results.

Oligomalt, a New Slowly Digestible Carbohydrate, Reduces Post-Prandial Glucose and Insulin Trajectories Compared to Maltodextrin across Different Population Characteristics: Double-Blind Randomized Controlled Trials in Healthy Individuals, People with Obesity, and People with Type 2 Diabetes.

We assessed the glucometabolic effects of oligomalt, a novel fully slowly digestible carbohydrate, compared with maltodextrin, in cross-over randomized controlled trials (NCT05058144; NCT05963594) involving healthy volunteers (HV), people with overweight or obesity (PwO), and people with type 2 diabetes (T2D). We tested 33 g and/or 50 g of oligomalt/maltodextrin, which were dissolved in 300 mL of water and consumed after fasting in the morning. The primary exploratory endpoint was the incremental area under the curve (iAUC) for postprandial glucose, assessed by frequent blood sampling over 3 h. Insulin levels were also assessed. In the HV cohort, a 4 h hydrogen breath test was performed with 15 g of inulin as a positive control. Analysis was performed by a mixed model. Oligomalt elicited a lower post-prandial glucose response compared to maltodextrin in HV (50 g, n = 15 [7 women], mean age/BMI 31 years/22.6 kg/m2), in PwO (33 g and 50 g, n = 26 [10 women], age/BMI 44 years/29.9 kg/m2, mean HbA1c 5.3%), and in people with T2D (50 g, n = 22 [13 women], age/BMI 61 years/31.8 kg/m2, HbA1c 7.4%), with significant reductions observed in PwO and T2D for the 0-1 h window (HV: -19% [p = 0.149]/PwO33g-38% [p = 0.0002]/PwO50g-28% [p = 0.0027]/T2D-38% [p < 0.0001]; the 0-2 h window (HV: -17% [p = 0.311]/PwO33g-34% [p = 0.0057]/PwO50g-21% [p = 0.0415]/T2D-37% [p < 0.0001]), and the 0-3 h window (HV: -15% [p = 0.386]/PwO33g-30% [p = 0.0213]/PwO50g0-19% [p = 0.0686]/T2D-37% [p = 0.0001]). The post-prandial insulin response was significantly lower, by 38-60%, across all populations, dose, and time points, with oligomalt. In HV, the breath-hydrogen pattern was comparable between oligomalt and maltodextrin, but increased significantly with inulin. These data support the glucometabolic advantages of oligomalt over maltodextrin, hence confirming it as a healthier carbohydrate, and underscoring its full digestibility. This therefore opens up the possibility for the incorporation of oligomalt in relevant food products/matrices.

Prolonged Consumption of A2 β-Casein Milk Reduces Symptoms Compared to A1 and A2 β-Casein Milk in Lactose Maldigesters: A Two-Week Adaptation Study.

Approximately 30% of milk protein is β-casein. We aimed to determine whether lactose maldigesters who chronically consumed two cups of A1/A2 milk (containing 75% A1 β-casein and 25% A2 β-casein) would adapt to have fewer intolerance symptoms, lower serum inflammatory markers, and/or altered glutathione levels similar to those consuming A2 milk (containing 100% A2 β-casein). A double-blinded, randomized, crossover trial was conducted. Sixteen confirmed lactose maldigesters consumed 250 mL of A1/A2 milk and A2 milk twice daily with meals for two weeks. At the end of the adaptation period on day 15, lactose maldigestion was measured after a challenge with the same milk used for adaptation (0.5 g of lactose per kg of body weight) with a hydrogen breath test. Fecal urgency was higher during the two-week consumption of A1/A2 milk compared to A2 milk (p = 0.04, n = 16). Bloating (p = 0.03, n = 16) and flatulence (p = 0.02, n = 16) were also higher on the 15th day with A1/A2 milk compared to A2 milk challenge. However, day-to-day symptoms, hydrogen, serum inflammatory markers, and antioxidant concentrations were not different after A1/A2 and A2 milk consumption adaptation periods. Adaptation over two weeks did not improve lactose digestion or tolerance of A1/A2 milk to match that of A2 milk.

만성 편두통에 대한 기능의학적 이해 및 치료적 접목

Chronic migraine, affecting approximately 2% of the global population, markedly diminishes quality of life and imposes significant societal costs, surpassing the impacts of episodic migraine. Conventional medical treatments leave about 30% of patients with persistent chronic migraine, some of whom fluctuate between episodic and chronic migraine states. A holistic, functional medicine approach may provide supplementary benefits for these individuals. Clinical imbalances often identified in chronic migraine patients—such as mitochondrial dysfunction, oxidative stress, gut microbiota dysbiosis, leaky gut syndrome, food intolerance, histamine syndrome, vitamin D deficiency, and autonomic nervous system imbalances—can be detected through specific functional medical assessments, including urine organic acid profiles, hair tissue mineral analysis, hydrogen breath tests, comprehensive blood tests, and heart rate variability tests. Integrative functional medical interventions, encompassing lifestyle modifications, oral and intravenous nutrition therapies, and the comprehensive 5R program (remove, replace, reinoculate, repair, rebalance) for gut health, could offer therapeutic benefits. This review delves into the functional medicine paradigm and its potential role in managing chronic migraine.

Fecal Coprococcus, hidden behind abdominal symptoms in patients with small intestinal bacterial overgrowth

BackgroundSmall intestinal bacterial overgrowth (SIBO) is the presence of an abnormally excessive amount of bacterial colonization in the small bowel. Hydrogen and methane breath test has been widely applied as a non-invasive method for SIBO. However, the positive breath test representative of bacterial overgrowth could also be detected in asymptomatic individuals.MethodsTo explore the relationship between clinical symptoms and gut dysbiosis, and find potential fecal biomarkers for SIBO, we compared the microbial profiles between SIBO subjects with positive breath test but without abdominal symptoms (PBT) and healthy controls (HC) using 16S rRNA amplicon sequencing.ResultsFecal samples were collected from 63 SIBO who complained of diarrhea, distension, constipation, or abdominal pain, 36 PBT, and 55 HC. For alpha diversity, the Shannon index of community diversity on the genus level showed a tendency for a slight increase in SIBO, while the Shannon index on the predicted function was significantly decreased in SIBO. On the genus level, significantly decreased Bacteroides, increased Coprococcus_2, and unique Butyrivibrio were observed in SIBO. There was a significant positive correlation between saccharolytic Coprococcus_2 and the severity of abdominal symptoms. Differently, the unique Veillonella in the PBT group was related to amino acid fermentation. Interestingly, the co-occurrence network density of PBT was larger than SIBO, which indicates a complicated interaction of genera. Coprococcus_2 showed one of the largest betweenness centrality in both SIBO and PBT microbiota networks. Pathway analysis based on the Kyoto Encyclopedia of Genes and Genome (KEGG) database reflected that one carbon pool by folate and multiple amino acid metabolism were significantly down in SIBO.ConclusionsThis study provides valuable insights into the fecal microbiota composition and predicted metabolic functional changes in patients with SIBO. Butyrivibrio and Coprococcus_2, both renowned for their role in carbohydrate fermenters and gas production, contributed significantly to the symptoms of the patients. Coprococcus’s abundance hints at its use as a SIBO marker. Asymptomatic PBT individuals show a different microbiome, rich in Veillonella. PBT’s complex microbial interactions might stabilize the intestinal ecosystem, but further study is needed due to the core microbiota similarities with SIBO. Predicted folate and amino acid metabolism reductions in SIBO merit additional validation.

MASLD can cause halitosis by small intestinal bacterial overgrowth.

Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) exhibit varying degrees of halitosis. The author speculated that small intestinal bacterial overgrowth (SIBO) might lead to MASLD and subsequent extra-oral halitosis and aimed to test this hypothesis. This retrospective cross-sectional study reviewed 885 extra-oral halitosis patients. Halitosis and exhaled dimethyl sulfide (DMS) were measured by organoleptic score (OLS) (0-5) and OralChroma, respectively. SIBO and MASLD were diagnosed by hydrogen breath test and Fibroscan combined with cardiometabolic criteria. In this study, 133/885 (15.05%) of the halitosis patients otherwise healthy had MASLD, while 87/133 (65.41%) of the MASLD patients were SIBO-positive. No significant differences were observed in physical parameters such as age, serum biochemical parameters such as lipids, or Fibroscan parameters between the SIBO-positive and SIBO-negative patients. However, the OLS was 4 (interquartile range: 3-4) and exhaled DMS level was 56 (43-75) parts per billion (ppb) in the SIBO-positive patients, significantly greater than 2 (2-3) and 43 (25-51) ppb in the SIBO-negative patients (both p < 0.001). Exhaled hydrogen levels positively correlated with the OLS and exhaled DMS levels (r = 0.774, r = 0.740, both p < 0.001). MASLD can cause halitosis by SIBO.

Lactase for infantile colic: A systematic review of randomized clinical trials.

Infantile colic is excessive crying for no apparent reason in an otherwise healthy infant. Although its physiopathology is not completely understood, therapies usually target gastrointestinal symptoms. This systematic review of randomized controlled trials (RCTs) analyzes the efficacy of lactase supplementation in infantile colic.PubMed, Embase, and Cochrane were searched for RCTs evaluating lactase supplementation in infants up to 6 months old with infantile colic. Out of six RCTs including 394 patients, three reported a significantly shorter crying time in the lactase group than in the placebo group, while the other three found no significant difference between groups. Of the two studies that performed the hydrogen breath test, only one reported a significant reduction in exhaled hydrogen levels.The pharmacological approach to infantile colic remains debatable, and new studies with standardized diagnostic criteria and outcomes are required to guide lactase supplementation in clinical practice.

Fructose malabsorption and fructan malabsorption are associated in patients with irritable bowel syndrome

BackgroundFood malabsorption and intolerance is implicated in gastrointestinal symptoms among patients with irritable bowel syndrome (IBS). Key triggers include fructose and fructan. Prior studies examined fructose and fructan malabsorption separately in IBS patients. None have concurrently assessed both within the same patient group. We aimed to investigate the association between fructose and fructan malabsorption in the same patients with IBS using hydrogen breath testing (HBT).MethodsWe retrospectively identified patients with IBS who underwent fructose and fructan HBTs and abstracted their results from the electronic medical record. Fructose and fructan HBTs were performed by administering a 25 g fructose solution or 10 g fructan solution, followed by breath hydrogen readings every 30 min for 3 h. Patients were positive for fructose or fructan malabsorption if breath hydrogen levels exceeded 20 ppm.ResultsOf 186 IBS patients, 71 (38.2%) were positive for fructose malabsorption and 91 (48.9%) were positive for fructan malabsorption. Of these patients, 42 (22.6%) were positive for fructose malabsorption and fructan malabsorption. Positive fructose HBT readings were significantly associated with positive fructan HBT readings (p = 0.0283). Patients positive for fructose malabsorption or fructan malabsorption had 1.951 times higher odds of testing positive for the other carbohydrate.ConclusionsOur results reveal a clinically significant association between fructose malabsorption and fructan malabsorption in patients with IBS. Fructan malabsorption should be assessed in patients with fructose malabsorption, and vice versa. Further studies are required to identify the mechanisms underlying our findings.

Small intestinal bacterial overgrowth in diabetic gastroenteropathy.

Although diabetic gastroenteropathy (DGE) is associated with small intestinal bacterial overgrowth (SIBO), most studies have evaluated SIBO with a hydrogen breath test, which may be affected by altered transit in DGE. The risk factors for the consequences of SIBO in DGE are poorly understood. We aimed to evaluate the prevalence of, risk factors for, and gastrointestinal symptoms associated with SIBO in patients with DGE. In 75 patients with DGE and dyspepsia, we tested for SIBO (≥105 colony forming units /mL of aerobic and/or anaerobic bacteria in a duodenal aspirate) and assessed gastric emptying (GE) of solids, symptoms during a GE study and during an enteral lipid challenge (300 kcal/2 h), and daily symptoms with a Gastroparesis Cardinal Symptom Index diary for 2 weeks. Symptoms and GE were compared in patients with versus without SIBO. Of 75 patients, 34 (45%) had SIBO, which was not associated with the use of proton pump inhibitors, daily symptoms, GE, or symptoms during a GE study. During enteral lipid challenge, severe nausea (p = 0.006), fullness (p = 0.02) and bloating (p = 0.009) were each associated with SIBO. Twenty patients (59%) with versus 13 (32%) without SIBO had at least one severe symptom during the lipid challenge (p = 0.006). Among patients with DGE 45% had SIBO, which was associated with symptoms during enteral lipid challenge but not with delayed GE, symptoms during a GE study, or daily symptoms. Perhaps bacterial products and even fatty acids are recognized by and activate mast cells that drive the increased lipid sensitivity in SIBO.

Small Intestine Bacterial Overgrowth is associated with increased Campylobacter and epithelial injury in duodenal biopsies of Bangladeshi children.

Small intestine bacterial overgrowth (SIBO) has been associated with enteric inflammation, linear growth stunting, and neurodevelopmental delays in children from low-income countries. Little is known about the histologic changes or epithelial adherent microbiota associated with SIBO. We sought to describe these relationships in a cohort of impoverished Bangladeshi children. Undernourished 12-18-month-old children underwent both glucose hydrogen breath testing for SIBO and duodenoscopy with biopsy. Biopsy samples were subject to both histological scoring and 16s rRNA sequencing. 118 children were enrolled with 16s sequencing data available on 53. Of 11 histological features, we found that SIBO was associated with one, enterocyte injury in the second part of the duodenum (R = 0.21, p = 0.02). SIBO was also associated with a significant increase in Campylobacter by 16s rRNA analysis (Log 2-fold change of 4.43; adjusted p = 1.9 x 10-6). These findings support the growing body of literature showing an association between SIBO and enteric inflammation and enterocyte injury and further delineate the subgroup of children with environmental enteric dysfunction who have SIBO. Further, they show a novel association between SIBO and Campylobacter. Mechanistic work is needed to understand the relationship between SIBO, enterocyte injury, and Campylobacter.

The role of intestinal microbiota in the development of dysfunction of the biliary system in children

Objective: to study the state of the intestinal and biliary microbiota in children with intestinal and gallbladder dysfunction and to determine the features of the component composition of the biliary microbiota. Methods: We examined 20 children with irritable bowel syndrome (IBS). The presence of small intestinal bacterial overgrowth (SIBO) syndrome was determined (using a hydrogen breath test with lactulose), microbial markers of the intestinal and biliary microbiota (using gas chromatography-mass spectrometry). We also performed microscopy of bile (phase-contrast light microscopy) obtained through duodenal intubation. Results: In all children with IBS, SIBO was verified in the small intestine, with insufficiency of the ileocecal valve in half of them, associated with hypomotor dyskinesia of the gallbladder. Microscopy of the bile revealed a large number of crystals and leukocytes. A study of microbial markers of intestinal and biliary microbiota in all children with IBS and SIBO revealed excessive bacterial associative growth of gram-negative opportunistic bacteria in combination with viruses of the Herpes family. An increase in the level of lipopolysaccharides (2 times higher than normal) and a deficiency of microbial markers of the main groups of microorganisms (anaerobic bacteria) responsible for metabolization processes in the enterohepatic circulation (plasmalogen less than 50 μg/ml) were recorded. Excessive growth of 28 species of opportunistic bacteria was detected in bile in diagnostically significant concentrations associated with hypomotor dysfunction of the gallbladder and lithogenicity of bile. Conclusion: A violation of the biliary microbiota was established with an increase in the proportion of gram-negative opportunistic bacteria, the spectrum of which was close to that of the intestine and their association with intestinal and biliary dyskinesia

Added Value of 13C Analysis in Breath Tests in H2-Negative Subjects to Diagnose Lactose Malabsorption: A Proof of Concept Study.

Diagnosing lactose malabsorption is usually based on hydrogen excretion in breath after a lactose challenge. However, a proportion of subjects with lactose malabsorption will not present a rise in hydrogen. Measuring excretion of methane or stable isotope labeled 13CO2 after ingestion of 13C-lactose has been proposed to mitigate this problem. The aim of the study was to assess the performance of measuring methane and 13CO2 in individuals with normal hydrogen excretion compared to a genetic lactase non-persistence test. Individuals referred for lactose breath testing and healthy controls were included. Participants received 13C-enriched lactose, performed breath testing, and underwent genotyping for a marker of lactase non-persistence (13910C*T). Using genotype as gold standard, the performance of measuring methane and 13CO2 excretion was assessed. 151 subjects participated in the study, 50 of which presented a lactase non-persistent genotype. Of these, 72% were correctly diagnosed through hydrogen excretion of ≥ 20ppm above baseline. In subjects with normal hydrogen excretion, cumulative 13C excretion had an area under the curve (AUC) of the receiver operating characteristics (ROC) curve of 0.852. Sensitivity was 93% and specificity was 51% for the current cutoff of 14.5%. The optimal cutoff was 12.65% (sensitivity 93%, specificity 70%). The ROC curve of peak methane had an AUC of 0.542 (sensitivity of 14%, specificity of 91% for cutoff ≥ 10ppm). In individuals with genetically demonstrated lactase non-persistence and negative hydrogen breath test, the use of 13C-lactose with measurement of 13CO2 excretion and hydrogen is a well-performing test to detect the lactose malabsorption and performs better than methane in our cohort.

Current views on the functional role of hydrogen and its kinetics in the human body

The purpose of this overview was to present historical data on the discovery of hydrogen and a brief summary of its physical properties that form the basis for its use in aeronautics. Information is provided on the use of hydrogen, a biologically neutral molecule, in medicine as a diagnostic indicator for penetrating wounds of the gastrointestinal tract, the determination of local blood flow using the hydrogen clearance method, the use of the hydrogen breath test for the diagnosis of malabsorption and carbohydrate intolerance, achlorhydria, the diagnosis of bacterial overgrowth syndrome, the assessment of biodegradation of magnesium-containing implants, the orocecal transit time, and during deep-sea diving. The reasons for the sharp increase in the doctors’ interest in studying the biological role of hydrogen after the discovery of its antioxidant properties by a group of Japanese scientists (2007) are analyzed. In order to increase antioxidant protection of the body, data from recent research on ways to increase its concentration in the body through the supply of exogenous gas by inhalation or by administering hydrogen-rich water or saline solution is presented. Particular attention is paid to a critical analysis of studies on the kinetics of hydrogen by different routes, its concentration in blood and tissues, inhalation, and the use of hydrogen-rich water. Based on an analysis of publications, that the use of molecular hydrogen to relieve oxidative stress in the tissues of the intestines, liver and lungs is most promising, since its highest concentration is found in these tissues. Fermentation of carbohydrates has also been shown to increase the production of hydrogen by the intestinal microbiota. Considering that a large number of molecular hydrogen generators appeared on the market, the data on the requirements for their safety are summarized. Considerations on the use of molecular hydrogen for the purpose of antioxidant protection of the body in cardiology, gastroenterology, pulmonology, and other areas of medicine are based on modern views on the mechanisms of antioxidant, anti-apoptotic, cytoprotective, and anti-inflammatory effects of hydrogen. Particular attention is paid to the analysis of experimental and clinical research on the use of hydrogen in acute and chronic lung lesions, therapy of acute and chronic COVID-19 infection.Conclusion. Based on an analysis of the literature and our own data, a conclusion was drawn on the safety and prospects of the clinical use of molecular hydrogen in a wide range of concentrations in many diseases with the pathogenesis based on oxidative stress. In particular, the need for additional research was highlighted to clarify the regimen, frequency, duration and concentrations of hydrogen used, and a personalized approach to the combination of endogenous (from the intestinal microbiota) and exogenous hydrogen in various diseases.

Efficacy and safety of rifaximin in patients with chronic intestinal pseudo-obstruction: a randomized, double-blind, placebo-controlled, phase II-a exploratory trial.

Chronic intestinal pseudo-obstruction (CIPO) is a rare intractable disease with limited treatment options. Small intestinal bacterial overgrowth (SIBO) often co-occurs with several diseases, including CIPO. While rifaximin (RFX) is effective in treating SIBO, its efficacy for CIPO remains unclear. Here, we aimed to investigate the efficacy and safety of RFX in adult patients with CIPO. Twelve patients were randomly assigned to receive RFX (400 mg three times daily, n=8) or a placebo (PBO, n=4) for 4 weeks. The global symptom score for abdominal bloating (GSS-bloating) and an original whole gastrointestinal symptoms score (O-WGSS) were collected, and a glucose hydrogen breath test (GHBT) and abdominal computed tomography (CT) were performed. No significant differences were observed in the primary endpoint. GSS-bloating improved by 75% and 25% in the PBO and RFX groups, respectively, and O-WGSS improved by 25% in both groups. No significant differences were observed in secondary and other endpoints, including the SIBO eradication rate in the GHBT and small intestinal volume on CT. In a post hoc analysis of SIBO-positive patients with CIPO (4/4 and 4/8 in the PBO and RFX groups), SIBO was eradicated in 25% and 75% of the patients (PBO and RFX groups, respectively) at the end of treatment, indicating a high eradication rate in the RFX group. Furthermore, the small intestinal gas volume decreased in the RFX group, and no severe adverse events occurred. Although no significant improvements were observed in subjective indicators, RFX may be beneficial in alleviating SIBO and reducing the small intestinal gas volume in SIBO-positive patients with CIPO.

A Study on the Glucose Breath Test Positivity Rate and Occurrence of Small Intestine Bacterial Overgrowth-Related Symptoms Caused by Long-Term Use of Proton Pump Inhibitor (PPI) Versus Potassium-Competitive Acid Blocker (P-CAB) in Elderly Patients: SIBO Between PPI and P-CAB.

Background/Aims: Long-term acid suppression with proton pump inhibitors (PPI) leads to hypochlorhydria and facilitates the growth of bacterial flora in the small intestine. Novel acid-suppressants called potassium-competitive acid blockers (P-CABs) seem to be superior to PPIs. However, data on the risk of small intestinal bacterial overgrowth (SIBO) in patients taking P-CABs are limited. Method: We retrospectively analyzed a consecutive series of patients with long-term acid-suppressant (PPIs or P-CABs) use for gastroesophageal reflux disease or nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy. All of them underwent endoscopic examinations and Helicobacter pylori testing and took PPIs or P-CABs for at least 3 months. Glucose hydrogen breath tests (GBT) were performed to check for SIBO, and newly developed SIBO-related symptoms including bloating, postprandial discomfort, diarrheas, and constipation, were evaluated. Results: A total of 142 patients were enrolled. Six patients were excluded due to equivocal Helicobacter pylori infection results. The frequency of positive GBTs was 31.7% (25/79) for PPI and 22.8% (13/57) for P-CAB use (p=0.15). Regarding GBT positivity, age-related factor was found to be significant in multivariate analysis (p=0.02). The results of multivariate analysis in cases of SIBO-related symptoms showed that GBT positivity and PPI use were significant (p < 0.01). Conclusion: Long-term use of gastric acid suppressants resulted in positive GBT in approximately 30% of patients, and the risk was particularly high in elderly patients. The occurrence of SIBO-related symptoms was significant in long-term use of PPIs and in patients with positive GBT.

Changes in gut microbiota and lactose intolerance symptoms before and after daily lactose supplementation in individuals with the lactase nonpersistent genotype

BackgroundApproximately 70%–100% of the Asian adult population is lactase nonpersistent (LNP). The literature shows that many individuals with the LNP-genotype can consume ≤12 g of lactose without experiencing gastrointestinal discomfort. Repetitive consumption of lactose may reduce intolerance symptoms via adaptation of the gut microbiota. ObjectiveThis study aimed to assess the effects of daily consumption of incremental lactose doses on microbiota composition and function, and intolerance symptoms. MethodsTwenty-five healthy adults of Asian origin, carrying the LNP-genotype were included in this 12-wk before and after intervention trial. Participants consumed gradually increasing lactose doses from 3 to 6 g to 12 g twice daily, each daily dose of 6 g, 12 g, or 24 g being provided for 4 consecutive weeks. Participants handed-in repeated stool samples and underwent a 25 g lactose challenge hydrogen breath test (HBT) before and after the 12-wk intervention. Daily gastrointestinal symptoms and total symptom scores (TSSs) during the lactose challenge were recorded. ResultsA significant increase from 5.5% ± 7.6% to 10.4% ± 9.6% was observed in Bifidobacterium relative abundance after the intervention (P = 0.009), accompanied by a 2-fold increase (570 ± 269 U/g; P < 0.001) in fecal β-galactosidase activity compared with baseline (272 ± 158 U/g). A 1.5-fold decrease (incremental area under the curve; P = 0.01) in expired hydrogen was observed during the second HBT (38 ± 35 ppm·min), compared with the baseline HBT (57 ± 38 ppm·min). There was a nonsignificant decrease in TSS (10.6 ± 8.3 before compared with 8.1 ± 7.2 after intervention; P = 0.09). Daily consumption of lactose was well tolerated, with mild to no gastrointestinal complaints reported during the intervention. ConclusionsIncreased levels of Bifidobacterium indicate an adaptation of the gut microbiota upon repetitive consumption of incremental doses of lactose, which was well tolerated as demonstrated by reduced expired hydrogen concentrations during the second 25-g lactose HBT. Bifidobacteria metabolize lactose without gas production thereby potentially reducing intestinal gas formation in the gut of individuals with the LNP-genotype. This increased lactose tolerance possibly lifts the necessity to remove nutrient-rich dairy foods completely from the diet.The trial is registered at the International Clinical Trials Registry Platform: NL9516. The effect of dietary lactose in lactase nonpersistent individuals on gut microbiota.

Hydrogen and methane breath testing for abdominal bloating of small intestinal origin

Abdominal bloating with or without excessive gas production and with or without abdominal distention is common, very bothersome for patients, and is poorly understood. Bloating can be associated with gastrointestinal disorders, nutrient malabsorption, and systemic illnesses. The origin of abdominal bloating is often unclear, though it is usually associated with food intake and bowel motility dysfunction. Often, food allergies, food intolerance, or food poisoning are considered by the patient or physician as potential causes for bloating. A common concern in the patient’s mind is that healthcare professionals will dismiss or misdiagnose their complaint. The limited understanding of the pathophysiology of bloating leads to current empirical management, and bloating is often characterized as a “functional” disorder. Bloating carries a heavy clinical, psychological, and economic burden. Proper diagnosis will provide the patient with peace of mind and lead to effective treatment. This review focuses on the mechanisms and management of abdominal bloating associated with different small intestinal disorders identified by non-invasive hydrogen and methane breath tests.