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European guideline on indications, performance, and clinical impact of hydrogen and methane breath tests in adult and pediatric patients: European Association for Gastroenterology, Endoscopy and Nutrition, European Society of Neurogastroenterology and Motility, and European Society for Paediatric Gastroenterology Hepatology and Nutrition consensus.
Hammer, HF, Fox, MR, Keller, J, Salvatore, S, Basilisco, G, Hammer, J, Lopetuso, L, Benninga, M, Borrelli, O, Dumitrascu, D, et al
United European gastroenterology journal. 2022;(1):15-40
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Abstract
INTRODUCTION Measurement of breath hydrogen (H2 ) and methane (CH4 ) excretion after ingestion of test-carbohydrates is used for different diagnostic purposes. There is a lack of standardization among centers performing these tests and this, together with recent technical developments and evidence from clinical studies, highlight the need for a European guideline. METHODS This consensus-based clinical practice guideline defines the clinical indications, performance, and interpretation of H2 -CH4 -breath tests in adult and pediatric patients. A balance between scientific evidence and clinical experience was achieved by a Delphi consensus that involved 44 experts from 18 European countries. Eighty eight statements and recommendations were drafted based on a review of the literature. Consensus (≥80% agreement) was reached for 82. Quality of evidence was evaluated using validated criteria. RESULTS The guideline incorporates new insights into the role of symptom assessment to diagnose carbohydrate (e.g., lactose) intolerances and recommends that breath tests for carbohydrate malabsorption require additional validated concurrent symptom evaluation to establish carbohydrate intolerance. Regarding the use of breath tests for the evaluation of oro-cecal transit time and suspected small bowel bacterial overgrowth, this guideline highlights confounding factors associated with the interpretation of H2 -CH4 -breath tests in these indications and recommends approaches to mitigate these issues. CONCLUSION This clinical practice guideline should facilitate pan-European harmonization of diagnostic approaches to symptoms and disorders, which are very common in specialist and primary care gastroenterology practice, both in adult and pediatric patients. In addition, it identifies areas of future research needs to clarify diagnostic and therapeutic approaches.
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Examination of hydrogen cross-feeders using a colonic microbiota model.
Smith, NW, Shorten, PR, Altermann, E, Roy, NC, McNabb, WC
BMC bioinformatics. 2021;(1):3
Abstract
BACKGROUND Hydrogen cross-feeding microbes form a functionally important subset of the human colonic microbiota. The three major hydrogenotrophic functional groups of the colon: sulphate-reducing bacteria (SRB), methanogens and reductive acetogens, have been linked to wide ranging impacts on host physiology, health and wellbeing. RESULTS An existing mathematical model for microbial community growth and metabolism was combined with models for each of the three hydrogenotrophic functional groups. The model was further developed for application to the colonic environment via inclusion of responsive pH, host metabolite absorption and the inclusion of host mucins. Predictions of the model, using two existing metabolic parameter sets, were compared to experimental faecal culture datasets. Model accuracy varied between experiments and measured variables and was most successful in predicting the growth of high relative abundance functional groups, such as the Bacteroides, and short chain fatty acid (SCFA) production. Two versions of the colonic model were developed: one representing the colon with sequential compartments and one utilising a continuous spatial representation. When applied to the colonic environment, the model predicted pH dynamics within the ranges measured in vivo and SCFA ratios comparable to those in the literature. The continuous version of the model simulated relative abundances of microbial functional groups comparable to measured values, but predictions were sensitive to the metabolic parameter values used for each functional group. Sulphate availability was found to strongly influence hydrogenotroph activity in the continuous version of the model, correlating positively with SRB and sulphide concentration and negatively with methanogen concentration, but had no effect in the compartmentalised model version. CONCLUSIONS Although the model predictions compared well to only some experimental measurements, the important features of the colon environment included make it a novel and useful contribution to modelling the colonic microbiota.
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Metal (Mo, W, Ti) Carbide Catalysts: Synthesis and Application as Alternative Catalysts for Dry Reforming of Hydrocarbons-A Review.
Czaplicka, N, Rogala, A, Wysocka, I
International journal of molecular sciences. 2021;(22)
Abstract
Dry reforming of hydrocarbons (DRH) is a pro-environmental method for syngas production. It owes its pro-environmental character to the use of carbon dioxide, which is one of the main greenhouse gases. Currently used nickel catalysts on oxide supports suffer from rapid deactivation due to sintering of active metal particles or the deposition of carbon deposits blocking the flow of gases through the reaction tube. In this view, new alternative catalysts are highly sought after. Transition metal carbides (TMCs) can potentially replace traditional nickel catalysts due to their stability and activity in DR processes. The catalytic activity of carbides results from the synthesis-dependent structural properties of carbides. In this respect, this review presents the most important methods of titanium, molybdenum, and tungsten carbide synthesis and the influence of their properties on activity in catalyzing the reaction of methane with carbon dioxide.
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Parahydrogen-Induced Polarization of Amino Acids.
Pravdivtsev, AN, Buntkowsky, G, Duckett, SB, Koptyug, IV, Hövener, JB
Angewandte Chemie (International ed. in English). 2021;(44):23496-23507
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Abstract
Nuclear magnetic resonance (NMR) has become a universal method for biochemical and biomedical studies, including metabolomics, proteomics, and magnetic resonance imaging (MRI). By increasing the signal of selected molecules, the hyperpolarization of nuclear spin has expanded the reach of NMR and MRI even further (e.g. hyperpolarized solid-state NMR and metabolic imaging in vivo). Parahydrogen (pH2 ) offers a fast and cost-efficient way to achieve hyperpolarization, and the last decade has seen extensive advances, including the synthesis of new tracers, catalysts, and transfer methods. The portfolio of hyperpolarized molecules now includes amino acids, which are of great interest for many applications. Here, we provide an overview of the current literature and developments in the hyperpolarization of amino acids and peptides.
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Intravenous Hydrogen Therapy With Intracisternal Magnesium Sulfate Infusion in Severe Aneurysmal Subarachnoid Hemorrhage.
Takeuchi, S, Kumagai, K, Toyooka, T, Otani, N, Wada, K, Mori, K
Stroke. 2021;(1):20-27
Abstract
BACKGROUND AND PURPOSE Poor-grade subarachnoid hemorrhage still has a poor prognosis. This randomized controlled clinical trial evaluated intracisternal magnesium sulfate infusion combined with intravenous hydrogen therapy in patients with poor-grade subarachnoid hemorrhage. METHODS Thirty-seven patients with poor-grade subarachnoid hemorrhage were randomized to Mg+H2, Mg, and control groups. Mg and Mg+H2 groups received intracisternal magnesium sulfate infusion (2.5 mmol/L) at 20 mL/h for 14 days. Mg+H2 group also received intravenous hydrogen-rich solution infusion for 14 days. Primary outcome measures were occurrence of delayed cerebral ischemia and cerebral vasospasm. Secondary outcome measures were modified Rankin Scale and Karnofsky performance status at 3 and 12 months, Barthel index at 12 months, and serum and cerebrospinal fluid malondialdehyde and neuron-specific enolase. RESULTS Serum neuron-specific enolase levels were significantly lower in the Mg+H2 group from days 3 to 14 than in the control group. Cerebrospinal fluid neuron-specific enolase levels were also significantly lower in the Mg+H2 group from days 3 to 7 than in the control group. Incidences of cerebral vasospasm and delayed cerebral ischemia were significantly higher in the control group than in other groups. Modified Rankin Scale and Karnofsky performance status did not significantly differ between the three groups at 3 months. Modified Rankin Scale scores 0 to 2 were more common in the Mg and Mg+H2 groups at 1 year. Barthel index was higher in the Mg+H2 group than in the control group. CONCLUSIONS Intracisternal magnesium sulfate infusion started immediately after surgery reduces the incidence of cerebral vasospasm and delayed cerebral ischemia and improves clinical outcomes without complications in patients with poor-grade subarachnoid hemorrhage. Intracisternal magnesium sulfate infusion combined with intravenous hydrogen therapy decreases serum malondialdehyde and neuron-specific enolase and improves Barthel index, indicating hydrogen has additional effects. Registration: URL: https://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000014696.
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Hydrogen Breath Tests: Are They Really Useful in the Nutritional Management of Digestive Disease?
Usai-Satta, P, Oppia, F, Lai, M, Cabras, F
Nutrients. 2021;(3)
Abstract
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.
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Combating Oxidative Stress and Inflammation in COVID-19 by Molecular Hydrogen Therapy: Mechanisms and Perspectives.
Alwazeer, D, Liu, FF, Wu, XY, LeBaron, TW
Oxidative medicine and cellular longevity. 2021;:5513868
Abstract
COVID-19 is a widespread global pandemic with nearly 185 million confirmed cases and about four million deaths. It is caused by an infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which primarily affects the alveolar type II pneumocytes. The infection induces pathological responses including increased inflammation, oxidative stress, and apoptosis. This situation results in impaired gas exchange, hypoxia, and other sequelae that lead to multisystem organ failure and death. As summarized in this article, many interventions and therapeutics have been proposed and investigated to combat the viral infection-induced inflammation and oxidative stress that contributes to the etiology and pathogenesis of COVID-19. However, these methods have not significantly improved treatment outcomes. This may partly be attributable to their inability at restoring redox and inflammatory homeostasis, for which molecular hydrogen (H2), an emerging novel medical gas, may complement. Herein, we systematically review the antioxidative, anti-inflammatory, and antiapoptotic mechanisms of H2. Its small molecular size and nonpolarity allow H2 to rapidly diffuse through cell membranes and penetrate cellular organelles. H2 has been demonstrated to suppress NF-κB inflammatory signaling and induce the Nrf2/Keap1 antioxidant pathway, as well as to improve mitochondrial function and enhance cellular bioenergetics. Many preclinical and clinical studies have demonstrated the beneficial effects of H2 in varying diseases, including COVID-19. However, the exact mechanisms, primary modes of action, and its true clinical effects remain to be delineated and verified. Accordingly, additional mechanistic and clinical research into this novel medical gas to combat COVID-19 complications is warranted.
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Dynamic modeling of anaerobic methane oxidation coupled to sulfate reduction: role of elemental sulfur as intermediate.
Hatzikioseyian, A, Bhattarai, S, Cassarini, C, Esposito, G, Lens, PNL
Bioprocess and biosystems engineering. 2021;(4):855-874
Abstract
The process dynamics of anaerobic oxidation of methane (AOM) coupled to sulfate reduction (SR), and the potential role of elemental sulfur as intermediate are presented in this paper. Thermodynamic screening and experimental evidence from the literature conclude that a prominent model to describe AOM-SR is based on the concept that anaerobic methane oxidation proceeds through the production of the intermediate elemental sulfur. Two microbial groups are involved in the process: (a) anaerobic methanotrophs (ANME-2) and (b) Desulfosarcina/Desulfococcus sulfur reducers cluster (DSS). In this work, a dynamic model was developed to explore the interactions between biotic and abiotic processes to simulate the microbial activity, the chemical composition and speciation of the liquid phase, and the gas phase composition in the reactor headspace. The model includes the microbial kinetics for the symbiotic growth of ANME-2 and DSS, mass transfer phenomena between the gas and liquid phase for methane, hydrogen sulfide, and carbon dioxide and acid-base reactions for bicarbonate, sulfide, and ammonium. A data set from batch experiments, running for 250 days in artificial seawater inoculated with sediment from Marine Lake Grevelingen (The Netherlands) was used to calibrate the model. The inherent characteristics of AOM-SR make the identification of the kinetic parameters difficult due to the high correlation between them. However, by meaningfully selecting a set of kinetic parameters, the model simulates successfully the experimental data for sulfate reduction and sulfide production. The model can be considered as the basic structure for simulating continuous flow three-phase engineered systems based on AOM-SR.
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Fermentative molecular biohydrogen production from cheese whey: present prospects and future strategy.
Rao, R, Basak, N
Applied biochemistry and biotechnology. 2021;(7):2297-2330
Abstract
Waste-dependent fermentative routes for biohydrogen production present a possible scenario to produce hydrogen gas on a large scale in a sustainable way. Cheese whey contains a high portion of organic carbohydrate and other organic acids, which makes it a feasible substrate for biohydrogen production. In the present review, recent research progress related to fermentative technologies, which explore the potentiality of cheese whey for biohydrogen production as an effective tool on a large scale, has been analyzed systematically. In addition, application of multiple response surface methodology tools such as full factorial design, Box-Behnken model, and central composite design during fermentative biohydrogen production to study the interactive effects of different bioprocess variables for higher biohydrogen yield in batch, fed-batch, and continuous mode is also discussed. The current paper also emphasizes computational fluid dynamics-based simulation designs, by which the substrate conversion efficiency of the cheese whey-based bioprocess and temperature distribution toward the turbulent flow of reaction liquid can be enhanced. The possible future developments toward higher process efficiency are outlined.
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Disentangling the syntrophic electron transfer mechanisms of Candidatus geobacter eutrophica through electrochemical stimulation and machine learning.
Yuan, H, Wang, X, Lin, TY, Kim, J, Liu, WT
Scientific reports. 2021;(1):15140
Abstract
Interspecies hydrogen transfer (IHT) and direct interspecies electron transfer (DIET) are two syntrophy models for methanogenesis. Their relative importance in methanogenic environments is still unclear. Our recent discovery of a novel species Candidatus Geobacter eutrophica with the genetic potential of IHT and DIET may serve as a model species to address this knowledge gap. To experimentally demonstrate its DIET ability, we performed electrochemical enrichment of Ca. G. eutrophica-dominating communities under 0 and 0.4 V vs. Ag/AgCl based on the presumption that DIET and extracellular electron transfer (EET) share similar metabolic pathways. After three batches of enrichment, Geobacter OTU650, which was phylogenetically close to Ca. G. eutrophica, was outcompeted in the control but remained abundant and active under electrochemical stimulation, indicating Ca. G. eutrophica's EET ability. The high-quality draft genome further showed high phylogenomic similarity with Ca. G. eutrophica, and the genes encoding outer membrane cytochromes and enzymes for hydrogen metabolism were actively expressed. A Bayesian network was trained with the genes encoding enzymes for alcohol metabolism, hydrogen metabolism, EET, and methanogenesis from dominant fermentative bacteria, Geobacter, and Methanobacterium. Methane production could not be accurately predicted when the genes for IHT were in silico knocked out, inferring its more important role in methanogenesis. The genomics-enabled machine learning modeling approach can provide predictive insights into the importance of IHT and DIET.