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Mohammadzadeh R, Mahnert A, Shinde T, Kumpitsch C, Weinberger V, Schmidt H, Moissl-Eichinger C. Age-related dynamics of predominant methanogenic archaea in the human gut microbiome. BMC Microbiol 2025; 25:193. [PMID: 40181255 PMCID: PMC11969853 DOI: 10.1186/s12866-025-03921-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Accepted: 03/20/2025] [Indexed: 04/05/2025] Open
Abstract
BACKGROUND The reciprocal relationship between aging and alterations in the gut microbiota is a subject of ongoing research. While the role of bacteria in the gut microbiome is well-documented, specific changes in the composition of methanogens during extreme aging and the impact of high methane production in general on health remain unclear. This study was designed to explore the association of predominant methanogenic archaea within the human gut and aging. METHODS Shotgun metagenomic data from the stool samples of young adults (n = 127, Age: 19-59 y), older adults (n = 86, Age: 60-99 y), and centenarians (n = 34, age: 100-109 years) were analyzed. RESULTS Our findings reveal a compelling link between age and the prevalence of high methanogen phenotype, while overall archaeal diversity diminishes. Surprisingly, the archaeal composition of methanogens in the microbiome of centenarians appears more akin to that of younger adults, showing an increase in Methanobrevibacter smithii, rather than Candidatus Methanobrevibacter intestini. Remarkably, Ca. M. intestini emerged as a central player in the stability of the archaea-bacteria network in adults, paving the way for M. smithii in older adults and centenarians. Notably, centenarians exhibit a highly complex and stable network of these two methanogens with other bacteria. The mutual exclusion between Lachnospiraceae and these methanogens throughout all age groups suggests that these archaeal communities may compensate for the age-related drop in Lachnospiraceae by co-occurring with Oscillospiraceae. CONCLUSIONS This study underscores the dynamics of archaeal microbiome in human physiology and aging. It highlights age-related shifts in methanogen composition, emphasizing the significance of both M. smithii and Ca. M. intestini and their partnership with butyrate-producing bacteria for potential enhanced health.
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Affiliation(s)
- Rokhsareh Mohammadzadeh
- Diagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Neue Stiftingtalstraße 6, Graz, 8010, Austria
| | - Alexander Mahnert
- Diagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Neue Stiftingtalstraße 6, Graz, 8010, Austria
| | - Tejus Shinde
- Diagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Neue Stiftingtalstraße 6, Graz, 8010, Austria
| | - Christina Kumpitsch
- Diagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Neue Stiftingtalstraße 6, Graz, 8010, Austria
| | - Viktoria Weinberger
- Diagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Neue Stiftingtalstraße 6, Graz, 8010, Austria
| | - Helena Schmidt
- Division of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria
| | - Christine Moissl-Eichinger
- Diagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Neue Stiftingtalstraße 6, Graz, 8010, Austria.
- BioTechMed, Graz, 8010, Austria.
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Woh PY, Chen Y, Kumpitsch C, Mohammadzadeh R, Schmidt L, Moissl-Eichinger C. Reevaluation of the gastrointestinal methanogenic archaeome in multiple sclerosis and its association with treatment. Microbiol Spectr 2025; 13:e0218324. [PMID: 39998261 PMCID: PMC11974365 DOI: 10.1128/spectrum.02183-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Accepted: 02/02/2025] [Indexed: 02/26/2025] Open
Abstract
The role of the gut archaeal microbiome (archaeome) in health and disease remains poorly understood. Methanogenic archaea have been linked to multiple sclerosis (MS), but prior studies were limited by small cohorts and inconsistent methodologies. To address this, we re-evaluated the association between methanogenic archaea and MS using metagenomic data from the International Multiple Sclerosis Microbiome Study. We analyzed gut microbiome profiles from 115 MS patients and 115 healthy household controls across Buenos Aires (27.8%), Edinburgh (33.9%), New York (10.4%), and San Francisco (27.8%). Metagenomic sequences were taxonomically classified using kraken2/bracken and a curated profiling database to detect archaea, specifically Methanobrevibacter species. Most MS patients were female (80/115), aged 25-72 years (median: 44.5), and 70% were undergoing treatment, including dimethyl fumarate (n = 21), fingolimod (n = 20), glatiramer acetate (n = 14), interferon (n = 18), natalizumab (n = 6), or ocrelizumab/rituximab (n = 1). We found no significant differences in overall archaeome profiles between MS patients and controls. However, treated MS patients exhibited higher abundances of Methanobrevibacter smithii and M. sp900766745 compared to untreated patients. Notably, M. sp900766745 abundance correlated with lower disease severity scores in treated patients. Our results suggest that gut methanogens are not directly associated with MS onset or progression but may reflect microbiome health during treatment. These findings highlight potential roles for M. smithii and M. sp900766745 in modulating treatment outcomes, warranting further investigation into their relevance to gut microbiome function and MS management.IMPORTANCEMultiple sclerosis (MS) is a chronic neuroinflammatory disease affecting the central nervous system, with approximately 2.8 million people diagnosed worldwide, mainly young adults aged 20-30 years. While recent studies have focused on bacterial changes in the MS microbiome, the role of gut archaea has been less explored. Previous research suggested a potential link between methanogenic archaea and MS disease status, but these findings remained inconclusive. Our study addresses this gap by investigating the gut archaeal composition in MS patients and examining how it changes in response to treatment. By focusing on methanogens, we aim to uncover novel insights into their role in MS, potentially revealing new biomarkers or therapeutic targets. This research is crucial for enhancing our understanding of the gut microbiome's impact on MS and improving patient management.
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Affiliation(s)
- Pei Yee Woh
- Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hong Kong, China
- Research Institute for Future Food (RiFood), The Hong Kong Polytechnic University, Hong Kong, China
| | - Yehao Chen
- Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hong Kong, China
| | - Christina Kumpitsch
- Diagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria
| | - Rokhsareh Mohammadzadeh
- Diagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria
| | - Laura Schmidt
- Diagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria
| | - Christine Moissl-Eichinger
- Diagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria
- BioTechMed Graz, Graz, Austria
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Silva BCD, Ramos GP, Barros LL, Ramos AFP, Domingues G, Chinzon D, Passos MDCF. DIAGNOSIS AND TREATMENT OF SMALL INTESTINAL BACTERIAL OVERGROWTH: AN OFFICIAL POSITION PAPER FROM THE BRAZILIAN FEDERATION OF GASTROENTEROLOGY. ARQUIVOS DE GASTROENTEROLOGIA 2025; 62:e24107. [PMID: 39968993 PMCID: PMC12043196 DOI: 10.1590/s0004-2803.24612024-107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/19/2024] [Accepted: 10/31/2024] [Indexed: 02/20/2025]
Abstract
BACKGROUND Small intestinal bacterial overgrowth (SIBO) is a condition characterized by an abnormal increase in bacterial population in the small intestine, leading to symptoms such as bloating, abdominal pain, distension, diarrhea, and eventually malabsorption. The diagnosis and management of SIBO remain challenging due to overlapping symptoms with other gastrointestinal disorders such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and coeliac disease. OBJECTIVE This article aims to review current evidence on the diagnosis and treatment of SIBO, with a focus on strategies suitable for the Brazilian healthcare system. METHODS A comprehensive literature review was performed, focusing on clinical guidelines, randomized controlled trials, and cohort studies concerning SIBO. Diagnostic methods, including breath tests and direct aspiration techniques, were critically analyzed. Treatment approaches, including antibiotics, dietary modifications, and probiotics, were reviewed. The recommendations were formulated based on a panel of gastroenterologists, members of the Brazilian Federation of Gastroenterology (FBG), with approval from the majority of the members. RESULTS Breath tests using glucose and lactulose remain the most commonly used non-invasive diagnostic tools, though they are subject to limitations such as false positives and false negatives. Treatment with rifaximin is effective in most cases of SIBO, while systemic antibiotics like metronidazole and ciprofloxacin are alternatives. Probiotics and dietary interventions, particularly low FODMAP diets, can complement antibiotic therapy. Long-term follow-up is essential due to the recurrence rate, which is common in SIBO patients. CONCLUSION Standardizing SIBO diagnosis and treatment in Brazil is essential to reduce diagnostic delays and optimize care, especially given the disparities and heterogeneity in clinical practice across the country. This article provides evidence-based recommendations to guide clinical practice. Further research is needed to refine diagnostic methods, explore novel treatment strategies, and better understand the specific characteristics of the Brazilian population.
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Affiliation(s)
| | | | - Luisa Leite Barros
- Faculdade de Medicina da Universidade de São Paulo, Departamento de Gastroenterologia, São Paulo, SP, Brasil
| | | | - Gerson Domingues
- Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
| | - Décio Chinzon
- Faculdade de Medicina da Universidade de São Paulo, Departamento de Gastroenterologia, São Paulo, SP, Brasil
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Heng W, Yin S, Chen Y, Gao W. Exhaled Breath Analysis: From Laboratory Test to Wearable Sensing. IEEE Rev Biomed Eng 2025; 18:50-73. [PMID: 39412981 PMCID: PMC11875904 DOI: 10.1109/rbme.2024.3481360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2024]
Abstract
Breath analysis and monitoring have emerged as pivotal components in both clinical research and daily health management, particularly in addressing the global health challenges posed by respiratory and metabolic disorders. The advancement of breath analysis strategies necessitates a multidisciplinary approach, seamlessly integrating expertise from medicine, biology, engineering, and materials science. Recent innovations in laboratory methodologies and wearable sensing technologies have ushered in an era of precise, real-time, and in situ breath analysis and monitoring. This comprehensive review elucidates the physical and chemical aspects of breath analysis, encompassing respiratory parameters and both volatile and non-volatile constituents. It emphasizes their physiological and clinical significance, while also exploring cutting-edge laboratory testing techniques and state-of-the-art wearable devices. Furthermore, the review delves into the application of sophisticated data processing technologies in the burgeoning field of breathomics and examines the potential of breath control in human-machine interaction paradigms. Additionally, it provides insights into the challenges of translating innovative laboratory and wearable concepts into mainstream clinical and daily practice. Continued innovation and interdisciplinary collaboration will drive progress in breath analysis, potentially revolutionizing personalized medicine through entirely non-invasive breath methodology.
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Jávor P, Donka T, Solli HS, Sándor L, Baráth B, Perényi D, Mohácsi Á, Török L, Hartmann P. Could exhaled methane be used as a possible indicator for hemodynamic changes in trauma induced hemorrhagic shock? Scientific basis supported by a case study. Injury 2024; 55 Suppl 3:111456. [PMID: 39300623 DOI: 10.1016/j.injury.2024.111456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 02/14/2024] [Accepted: 02/25/2024] [Indexed: 09/22/2024]
Abstract
INTRODUCTION Identification of severe blood loss and hemorrhagic shock in polytrauma patients poses a key challenge for trauma teams across the world, as there are just a few objective parameters, on which clinicians can rely. We investigated the relationship between exhaled air methane (CH4) concentration and blood loss in a polytrauma patient. Decreased blood flow in the superior mesenteric artery (SMA) is one of the first compensatory responses to blood loss. Gases produced by the anaerobic flora of the intestinal segment supplied by the SMA are the primary source of exhaled CH4, which diffuses through the intestinal microvessels into the circulation and is finally eliminated through the lungs. We hypothesized that diminution of exhaled CH4 indicates blood loss and tested our theory in a severely injured patient. METHODS Exhaled CH4 concentrations of a severely injured patient were measured using a photoacoustic spectroscope (PAS) attached to the exhalation side of the breathing circuit. The primary objective was to investigate the relationship between exhaled CH4 and conventional indicators of hemorrhage including hemoglobin (Hb) levels, base deficit (BD) values and vital parameters (heart rate and systolic blood pressure) in the early phase of in-hospital care (first 4 h). RESULTS A severely injured patient was admitted with unstable hemodynamic parameters and incomplete left lower limb amputation, (Injury Severity Score: 38, 74/36 mmHg, 76 bpm). At the time of arrival, considerably lower CH4 levels were detected (22,800 PAU) in the exhaled air. During the first 4 h fluid and massive blood resuscitation, the exhaled CH4 levels were continuously rising in parallel with Htc and Hb values. Corresponding to these changes, BD values displayed a decreasing tendency. DISCUSSION Our study was conducted to characterize the changes in exhaled air CH4 concentration in response to hemorrhagic shock and to provide data on a viable clinical use of an experimental technique. According to our results, the real-time detection of exhaled air CH4 concentration is an applicable and promising technique for the early detection of bleeding and hemorrhagic shock in severely injured patients. Further research on large sample size and refinement of the PAS technique is required.
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Affiliation(s)
- Péter Jávor
- Department of Traumatology, University of Szeged, Szeged, Hungary, Semmelweis street 6., Szeged, 6725 Hungary
| | - Tibor Donka
- National Academy of Scientist Education, Pacsirta str 31., Szeged, 6724 Hungary
| | - Hanne Sofie Solli
- Department of Traumatology, University of Szeged, Szeged, Hungary, Semmelweis street 6., Szeged, 6725 Hungary
| | - Lilla Sándor
- Department of Traumatology, University of Szeged, Szeged, Hungary, Semmelweis street 6., Szeged, 6725 Hungary
| | - Bálint Baráth
- Department of Traumatology, University of Szeged, Szeged, Hungary, Semmelweis street 6., Szeged, 6725 Hungary; Doctoral School of Multidisciplinary Medical Sciences, University of Szeged, Szeged, Hungary, Dóm square 9., Szeged, 6720 Hungary
| | - Domonkos Perényi
- National Academy of Scientist Education, Pacsirta str 31., Szeged, 6724 Hungary
| | - Árpád Mohácsi
- MTA - SZTE Research Group on Photoacoustic Spectroscopy, University of Szeged, Szeged Hungary, Dóm tér 9., Szeged, 6720 Hungary
| | - László Török
- Department of Traumatology, University of Szeged, Szeged, Hungary, Semmelweis street 6., Szeged, 6725 Hungary; Department of Sports Medicine, University of Szeged, Szeged, Hungary, Semmelweis utca 6., Szeged, 6725 Hungary
| | - Petra Hartmann
- Department of Traumatology, University of Szeged, Szeged, Hungary, Semmelweis street 6., Szeged, 6725 Hungary.
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Duller S, Vrbancic S, Szydłowski Ł, Mahnert A, Blohs M, Predl M, Kumpitsch C, Zrim V, Högenauer C, Kosciolek T, Schmitz RA, Eberhard A, Dragovan M, Schmidberger L, Zurabischvili T, Weinberger V, Moser AM, Kolb D, Pernitsch D, Mohammadzadeh R, Kühnast T, Rattei T, Moissl-Eichinger C. Targeted isolation of Methanobrevibacter strains from fecal samples expands the cultivated human archaeome. Nat Commun 2024; 15:7593. [PMID: 39217206 PMCID: PMC11366006 DOI: 10.1038/s41467-024-52037-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Accepted: 08/21/2024] [Indexed: 09/04/2024] Open
Abstract
Archaea are vital components of the human microbiome, yet their study within the gastrointestinal tract (GIT) is limited by the scarcity of cultured representatives. Our study presents a method for the targeted enrichment and isolation of methanogenic archaea from human fecal samples. The procedure combines methane breath testing, in silico metabolic modeling, media optimization, FACS, dilution series, and genomic sequencing through Nanopore technology. Additional analyzes include the co-cultured bacteriome, comparative genomics of archaeal genomes, functional comparisons, and structure-based protein function prediction of unknown differential traits. Successful establishment of stable archaeal cultures from 14 out of 16 fecal samples yielded nine previously uncultivated strains, eight of which are absent from a recent archaeome genome catalog. Comparative genomic and functional assessments of Methanobrevibacter smithii and Candidatus Methanobrevibacter intestini strains from individual donors revealed features potentially associated with gastrointestinal diseases. Our work broadens available archaeal representatives for GIT studies, and offers insights into Candidatus Methanobrevibacter intestini genomes' adaptability in critical microbiome contexts.
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Affiliation(s)
- Stefanie Duller
- D&R Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria
| | - Simone Vrbancic
- D&R Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria
| | - Łukasz Szydłowski
- Malopolska Centre of Biotechnology, Jagiellonian University in Krakow, Krakow, Poland
- Sano Centre for Computational Medicine, Krakow, Poland
| | - Alexander Mahnert
- D&R Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria
- BioTechMed Graz, Graz, Austria
| | - Marcus Blohs
- D&R Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria
| | - Michael Predl
- Centre for Microbiology and Environmental Systems Science, University of Vienna, Vienna, Austria
- Doctoral School Microbiology and Environmental Science, University of Vienna, Vienna, Austria
| | - Christina Kumpitsch
- D&R Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria
- BioTechMed Graz, Graz, Austria
| | - Verena Zrim
- Center for Medical Research, Medical University of Graz, Graz, Austria
| | - Christoph Högenauer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Tomasz Kosciolek
- Malopolska Centre of Biotechnology, Jagiellonian University in Krakow, Krakow, Poland
- Sano Centre for Computational Medicine, Krakow, Poland
- Department of Data Science and Engineering, Silesian University of Technology, Gliwice, Poland
| | - Ruth A Schmitz
- Institute for General Microbiology, Christian Albrechts University, Kiel, Germany
| | - Anna Eberhard
- D&R Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria
| | - Melanie Dragovan
- D&R Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria
| | - Laura Schmidberger
- D&R Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria
| | - Tamara Zurabischvili
- D&R Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria
| | - Viktoria Weinberger
- D&R Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria
| | - Adrian Mathias Moser
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Dagmar Kolb
- Core Facility Ultrastructure Analysis, Medical University of Graz, Graz, Austria
- Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria
| | - Dominique Pernitsch
- Core Facility Ultrastructure Analysis, Medical University of Graz, Graz, Austria
| | - Rokhsareh Mohammadzadeh
- D&R Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria
| | - Torben Kühnast
- D&R Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria
| | - Thomas Rattei
- Centre for Microbiology and Environmental Systems Science, University of Vienna, Vienna, Austria
| | - Christine Moissl-Eichinger
- D&R Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria.
- BioTechMed Graz, Graz, Austria.
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Kato T, Tanaka T, Uchida K. Detection of PPB-Level H 2S Concentrations in Exhaled Breath Using Au Nanosheet Sensors with Small Variability, High Selectivity, and Long-Term Stability. ACS Sens 2024; 9:708-716. [PMID: 38336360 PMCID: PMC10898455 DOI: 10.1021/acssensors.3c01944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 12/13/2023] [Accepted: 12/18/2023] [Indexed: 02/12/2024]
Abstract
The continuous monitoring of hydrogen sulfide (H2S) in exhaled breath enables the detection of health issues such as halitosis and gastrointestinal problems. However, H2S sensors with high selectivity and parts per billion-level detection capability, which are essential for breath analysis, and facile fabrication processes for their integration with other devices are lacking. In this study, we demonstrated Au nanosheet H2S sensors with high selectivity, ppb-level detection capability, and high uniformity by optimizing their fabrication processes: (1) insertion of titanium nitride (TiN) as an adhesion layer to prevent Au agglomeration on the oxide substrate and (2) N2 annealing to improve nanosheet crystallinity. The fabricated Au nanosheets successfully detected H2S at concentrations as low as 5.6 ppb, and the estimated limit of detection was 0.5 ppb, which is superior to that of the human nose (8-13 ppb). In addition, the sensors detected H2S in the exhaled breath of simulated patients at concentrations as low as 175 ppb while showing high selectivity against interfering molecules, such as H2, alcohols, and humidity. Since Au nanosheets with uniform sensor characteristics enable easy device integration, the proposed sensor will be useful for facile health checkups based on breath analysis upon its integration into mobile devices.
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Affiliation(s)
- Taro Kato
- Department of Materials Engineering, The University of Tokyo, Tokyo 113-8656, Japan
| | - Takahisa Tanaka
- Department of Materials Engineering, The University of Tokyo, Tokyo 113-8656, Japan
| | - Ken Uchida
- Department of Materials Engineering, The University of Tokyo, Tokyo 113-8656, Japan
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Claypool DJ, Zhang YG, Xia Y, Sun J. Conditional Vitamin D Receptor Deletion Induces Fungal and Archaeal Dysbiosis and Altered Metabolites. Metabolites 2024; 14:32. [PMID: 38248835 PMCID: PMC10819266 DOI: 10.3390/metabo14010032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 12/24/2023] [Accepted: 12/28/2023] [Indexed: 01/23/2024] Open
Abstract
A vitamin D receptor (VDR) deficiency leads to the dysbiosis of intestinal bacteria and is associated with various diseases, including cancer, infections, and inflammatory bowel disease. However, the impact of a VDR deficiency on fungi and archaea is unknown. We conditionally deleted the VDR in Paneth cells (VDRΔPC), intestinal epithelial cells (VDRΔIEC), or myeloid cells (VDRΔLyz) in mice and collected feces for shotgun metagenomic sequencing and untargeted metabolomics. We found that fungi were significantly altered in each knockout (KO) group compared to the VDRLoxp control. The VDRΔLyz mice had the most altered fungi species (three depleted and seven enriched), followed by the VDRΔPC mice (six depleted and two enriched), and the VDRΔIEC mice (one depleted and one enriched). The methanogen Methanofollis liminatans was enriched in the VDRΔPC and VDRΔLyz mice and two further archaeal species (Thermococcus piezophilus and Sulfolobus acidocaldarius) were enriched in the VDRΔLyz mice compared to the Loxp group. Significant correlations existed among altered fungi, archaea, bacteria, and viruses in the KO mice. Functional metagenomics showed changes in several biologic functions, including decreased sulfate reduction and increased biosynthesis of cobalamin (vitamin B12) in VDRΔLyz mice relative to VDRLoxp mice. Fecal metabolites were analyzed to examine the involvement of sulfate reduction and other pathways. In conclusion, a VDR deficiency caused the formation of altered fungi and archaea in a tissue- and sex-dependent manner. These results provide a foundation about the impact of a host factor (e.g., VDR deficiency) on fungi and archaea. It opens the door for further studies to determine how mycobiome and cross-kingdom interactions in the microbiome community and metabolites contribute to the risk of certain diseases.
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Affiliation(s)
- Duncan J. Claypool
- Department of Medicine, University of Illinois Chicago, Chicago, IL 60612, USA; (D.J.C.); (Y.-G.Z.)
- Department of Bioengineering, University of Illinois Chicago, Chicago, IL 60607, USA
| | - Yong-Guo Zhang
- Department of Medicine, University of Illinois Chicago, Chicago, IL 60612, USA; (D.J.C.); (Y.-G.Z.)
| | - Yinglin Xia
- Department of Medicine, University of Illinois Chicago, Chicago, IL 60612, USA; (D.J.C.); (Y.-G.Z.)
- Jesse Brown VA Medical Center, Chicago, IL 60612, USA
| | - Jun Sun
- Department of Medicine, University of Illinois Chicago, Chicago, IL 60612, USA; (D.J.C.); (Y.-G.Z.)
- Department of Bioengineering, University of Illinois Chicago, Chicago, IL 60607, USA
- Jesse Brown VA Medical Center, Chicago, IL 60612, USA
- Department of Microbiology and Immunology, University of Illinois Chicago, Chicago, IL 60612, USA
- UIC Cancer Center, University of Illinois Chicago, Chicago, IL 60612, USA
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Wang T, Leibrock N, Plugge CM, Smidt H, Zoetendal EG. In vitro interactions between Blautia hydrogenotrophica, Desulfovibrio piger and Methanobrevibacter smithii under hydrogenotrophic conditions. Gut Microbes 2023; 15:2261784. [PMID: 37753963 PMCID: PMC10538451 DOI: 10.1080/19490976.2023.2261784] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Accepted: 09/15/2023] [Indexed: 09/28/2023] Open
Abstract
Methanogens, reductive acetogens and sulfate-reducing bacteria play an important role in disposing of hydrogen in gut ecosystems. However, how they interact with each other remains largely unknown. This in vitro study cocultured Blautia hydrogenotrophica (reductive acetogen), Desulfovibrio piger (sulfate reducer) and Methanobrevibacter smithii (methanogen). Results revealed that these three species coexisted and did not compete for hydrogen in the early phase of incubations. Sulfate reduction was not affected by B. hydrogenotrophica and M. smithii. D. piger inhibited the growth of B. hydrogenotrophica and M. smithii after 10 h incubations, and the inhibition on M. smithii was associated with increased sulfide concentration. Remarkably, M. smithii growth lag phase was shortened by coculturing with B. hydrogenotrophica and D. piger. Formate was rapidly used by M. smithii under high acetate concentration. Overall, these findings indicated that the interactions of the hydrogenotrophic microbes are condition-dependent, suggesting their interactions may vary in gut ecosystems.
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Affiliation(s)
- Taojun Wang
- Laboratory of Microbiology, Wageningen University & Research, Wageningen, The Netherlands
- Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA
| | - Nils Leibrock
- Laboratory of Microbiology, Wageningen University & Research, Wageningen, The Netherlands
| | - Caroline M. Plugge
- Laboratory of Microbiology, Wageningen University & Research, Wageningen, The Netherlands
- Wetsus European Centre of Excellence for Sustainable Water Technology, Leeuwarden, The Netherlands
| | - Hauke Smidt
- Laboratory of Microbiology, Wageningen University & Research, Wageningen, The Netherlands
| | - Erwin G. Zoetendal
- Laboratory of Microbiology, Wageningen University & Research, Wageningen, The Netherlands
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Keppler F, Boros M, Polag D. Radical-Driven Methane Formation in Humans Evidenced by Exogenous Isotope-Labeled DMSO and Methionine. Antioxidants (Basel) 2023; 12:1381. [PMID: 37507920 PMCID: PMC10376501 DOI: 10.3390/antiox12071381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2023] [Revised: 06/29/2023] [Accepted: 07/01/2023] [Indexed: 07/30/2023] Open
Abstract
Methane (CH4), which is produced endogenously in animals and plants, was recently suggested to play a role in cellular physiology, potentially influencing the signaling pathways and regulatory mechanisms involved in nitrosative and oxidative stress responses. In addition, it was proposed that the supplementation of CH4 to organisms may be beneficial for the treatment of several diseases, including ischemia, reperfusion injury, and inflammation. However, it is still unclear whether and how CH4 is produced in mammalian cells without the help of microorganisms, and how CH4 might be involved in physiological processes in humans. In this study, we produced the first evidence of the principle that CH4 is formed non-microbially in the human body by applying isotopically labeled methylated sulfur compounds, such as dimethyl sulfoxide (DMSO) and methionine, as carbon precursors to confirm cellular CH4 formation. A volunteer applied isotopically labeled (2H and 13C) DMSO on the skin, orally, and to blood samples. The monitoring of stable isotope values of CH4 convincingly showed the conversion of the methyl groups, as isotopically labeled CH4 was formed during all experiments. Based on these results, we considered several hypotheses about endogenously formed CH4 in humans, including physiological aspects and stress responses involving reactive oxygen species (ROS). While further and broader validation studies are needed, the results may unambiguously serve as a proof of concept for the endogenous formation of CH4 in humans via a radical-driven process. Furthermore, these results might encourage follow-up studies to decipher the potential physiological role of CH4 and its bioactivity in humans in more detail. Of particular importance is the potential to monitor CH4 as an oxidative stress biomarker if the observed large variability of CH4 in breath air is an indicator of physiological stress responses and immune reactions. Finally, the potential role of DMSO as a radical scavenger to counteract oxidative stress caused by ROS might be considered in the health sciences. DMSO has already been investigated for many years, but its potential positive role in medical use remains highly uncertain.
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Affiliation(s)
- Frank Keppler
- Institute of Earth Sciences, Heidelberg University, D-69120 Heidelberg, Germany
- Heidelberg Center for the Environment (HCE), Heidelberg University, D-69120 Heidelberg, Germany
| | - Mihály Boros
- Institute of Surgical Research, University of Szeged, H-6724 Szeged, Hungary
| | - Daniela Polag
- Institute of Earth Sciences, Heidelberg University, D-69120 Heidelberg, Germany
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11
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Mion F, Subtil F, Ropert A, Jouet P. Does Single Fasting Methane Levels Really Detect Intestinal Methanogen Overgrowth? Am J Gastroenterol 2023; 118:1299-1300. [PMID: 37377266 DOI: 10.14309/ajg.0000000000002279] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/29/2023]
Affiliation(s)
- François Mion
- Digestive Physiology, Hospices Civils de Lyon, Université de Lyon, Lyon, France
| | - Fabien Subtil
- Biostatistical Department, Hospices Civils de Lyon, LBBE, Université de Lyon, Lyon, France
| | - Alain Ropert
- Gastroenterology and Physiology Department, CHU de Rennes, Rennes, France
| | - Pauline Jouet
- Gastroenterology Department, Hôpital Avicenne, APHP, Bobigny, France
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12
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Campbell A, Gdanetz K, Schmidt AW, Schmidt TM. H 2 generated by fermentation in the human gut microbiome influences metabolism and competitive fitness of gut butyrate producers. MICROBIOME 2023; 11:133. [PMID: 37322527 PMCID: PMC10268494 DOI: 10.1186/s40168-023-01565-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 05/03/2023] [Indexed: 06/17/2023]
Abstract
BACKGROUND Hydrogen gas (H2) is a common product of carbohydrate fermentation in the human gut microbiome and its accumulation can modulate fermentation. Concentrations of colonic H2 vary between individuals, raising the possibility that H2 concentration may be an important factor differentiating individual microbiomes and their metabolites. Butyrate-producing bacteria (butyrogens) in the human gut usually produce some combination of butyrate, lactate, formate, acetate, and H2 in branched fermentation pathways to manage reducing power generated during the oxidation of glucose to acetate and carbon dioxide. We predicted that a high concentration of intestinal H2 would favor the production of butyrate, lactate, and formate by the butyrogens at the expense of acetate, H2, and CO2. Regulation of butyrate production in the human gut is of particular interest due to its role as a mediator of colonic health through anti-inflammatory and anti-carcinogenic properties. RESULTS For butyrogens that contained a hydrogenase, growth under a high H2 atmosphere or in the presence of the hydrogenase inhibitor CO stimulated production of organic fermentation products that accommodate reducing power generated during glycolysis, specifically butyrate, lactate, and formate. Also as expected, production of fermentation products in cultures of Faecalibacterium prausnitzii strain A2-165, which does not contain a hydrogenase, was unaffected by H2 or CO. In a synthetic gut microbial community, addition of the H2-consuming human gut methanogen Methanobrevibacter smithii decreased butyrate production alongside H2 concentration. Consistent with this observation, M. smithii metabolic activity in a large human cohort was associated with decreased fecal butyrate, but only during consumption of a resistant starch dietary supplement, suggesting the effect may be most prominent when H2 production in the gut is especially high. Addition of M. smithii to the synthetic communities also facilitated the growth of E. rectale, resulting in decreased relative competitive fitness of F. prausnitzii. CONCLUSIONS H2 is a regulator of fermentation in the human gut microbiome. In particular, high H2 concentration stimulates production of the anti-inflammatory metabolite butyrate. By consuming H2, gut methanogenesis can decrease butyrate production. These shifts in butyrate production may also impact the competitive fitness of butyrate producers in the gut microbiome. Video Abstract.
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Affiliation(s)
- Austin Campbell
- Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, 48109, USA
| | - Kristi Gdanetz
- Department of Plant, Soil, and Microbial Sciences, Michigan State University, East Lansing, MI, 48824, USA
| | - Alexander W Schmidt
- Department of Internal Medicine, Division of Infectious Diseases, University of Michigan, MI, 48109, Ann Arbor, USA
| | - Thomas M Schmidt
- Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, 48109, USA.
- Department of Ecology & Evolutionary Biology, University of Michigan, MI, 48109, Ann Arbor, USA.
- Department of Internal Medicine, Division of Infectious Diseases, University of Michigan, MI, 48109, Ann Arbor, USA.
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13
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Plauzolles A, Uras S, Pénaranda G, Bonnet M, Dukan P, Retornaz F, Halfon P. Small Intestinal Bacterial Overgrowths and Intestinal Methanogen Overgrowths Breath Testing in a Real-Life French Cohort. Clin Transl Gastroenterol 2023; 14:e00556. [PMID: 36515897 PMCID: PMC10132713 DOI: 10.14309/ctg.0000000000000556] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Accepted: 12/02/2022] [Indexed: 12/15/2022] Open
Abstract
INTRODUCTION Breath testing has become a widely used tool to diagnose small intestinal bacterial overgrowths (SIBOs) and intestinal methanogen overgrowths (IMOs) in clinical settings. Owing to the heterogeneity in clinical manifestations and lack of standardization among centers performing breath testing, SIBO and IMO can be easily overlooked by the clinician. We studied the prevalence and symptoms of SIBO/IMO in French patients referred for breath testing after seeking medical advice. METHODS Breath test data and symptoms of 331 patients were assessed for SIBO/IMO using the H 2 /CH 4 lactulose breath test (LBT). Wilcoxon test or χ 2 test were used to compare patients with SIBO/IMO with patients without SIBO/IMO. LBT positive patients (H 2 +, CH 4 +, and CH 4 +/H 2 +) were compared using Kruskal-Wallis test for continuous data or χ 2 test for categorical data. RESULTS Among the 186 (68.1%) patients tested positive for an overgrowth with 40.3%, 47.3%, and 12.4% for H 2 +, CH 4 + and CH 4 +/H 2 +, respectively, the presence of diarrhea was significantly increased in hydrogen type overgrowths ( P < 0.001). No significant difference according to age, gender, and symptoms was associated with a positive test except for joint pain that was less prevalent among LBT positive patients ( P = 0.038). In 86.5% of IMOs, positivity with CH 4 values ≥10 ppm could be identified at baseline. DISCUSSION There are little discriminating symptoms that can help the clinician to identify patients likely to have a SIBO/IMO. However, SIBO/IMOs remain a common disorder widely underdiagnosed that need further studies to better apprehend functional bowel disorders.
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Affiliation(s)
- Anne Plauzolles
- Clinical Research and R&D Department, Laboratoire Européen Alphabio Biogroup, Marseille, France
| | - Stella Uras
- Clinical Research and R&D Department, Laboratoire Européen Alphabio Biogroup, Marseille, France
- Faculty of Sciences, Aix-Marseille University, Marseille, France
| | - Guillaume Pénaranda
- Clinical Research and R&D Department, Laboratoire Européen Alphabio Biogroup, Marseille, France
| | - Marion Bonnet
- Clinical Research and R&D Department, Laboratoire Européen Alphabio Biogroup, Marseille, France
| | - Patrick Dukan
- Infectious and Internal Medicine Department, Hôpital Européen Marseille, Marseille, France
| | - Frédérique Retornaz
- Infectious and Internal Medicine Department, Hôpital Européen Marseille, Marseille, France
| | - Philippe Halfon
- Clinical Research and R&D Department, Laboratoire Européen Alphabio Biogroup, Marseille, France
- Infectious and Internal Medicine Department, Hôpital Européen Marseille, Marseille, France
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14
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Carnero EA, Bock CP, Liu Y, Corbin K, Wohlers-Kariesch E, Ruud K, Moon J, Marcus A, Krajmalnik-Brown R, Muraviev A, Vodopyanov KL, Smith SR. Measurement of 24-h continuous human CH 4 release in a whole room indirect calorimeter. J Appl Physiol (1985) 2023; 134:766-776. [PMID: 36794690 PMCID: PMC10027086 DOI: 10.1152/japplphysiol.00705.2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 01/19/2023] [Accepted: 01/31/2023] [Indexed: 02/17/2023] Open
Abstract
We describe the technology and validation of a new whole room indirect calorimeter (WRIC) methodology to quantify volume of methane (VCH4) released from the human body over 24 h concurrently with the assessment of energy expenditure and substrate utilization. The new system extends the assessment of energy metabolism by adding CH4, a downstream product of microbiome fermentation that could contribute to energy balance. Our new system consists of an established WRIC combined with the addition of off-axis integrated-cavity output spectroscopy (OA-ICOS) to measure CH4 concentration ([CH4]). Development, validation, and reliability of the system included environmental experiments to measure the stability of the atmospheric [CH4], infusing CH4 into the WRIC and human cross-validation studies comparing [CH4] quantified by OA-ICOS and mid-infrared dual-comb spectroscopy (MIR DCS).Our infusion data indicated that the system measured 24-h [CH4] and VCH4 with high sensitivity, reliability, and validity. Cross-validation studies showed good agreement between OA-ICOS and MIR DCS technologies (r = 0.979, P < 0.0001). Human data revealed 24-h VCH4 was highly variable between subjects and within/between days. Finally, our method to quantify VCH4 released by breath or colon suggested that over 50% of the CH4 was eliminated through the breath. The method allows, for the first time, measurement of 24-h VCH4 (in kcal) and therefore the measurement of the proportion of human energy intake fermented to CH4 by the gut microbiome and released via breath or from the intestine; also, it allows us to track the effects of dietary, probiotic, bacterial, and fecal microbiota transplantation on VCH4.NEW & NOTEWORTHY This is the first time that continuous assessment of CH4 is reported in parallel with measurements of O2 consumption and CO2 production inside a whole room indirect calorimeter in humans and over 24 h. We provide a detailed description of the whole system and its parts. We carried out studies of reliability and validity of the whole system and its parts. CH4 is released in humans during daily activities.
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Affiliation(s)
- E. A. Carnero
- Translational Research Institute, AdventHealth, Orlando, Florida, United States
| | - C. P. Bock
- Translational Research Institute, AdventHealth, Orlando, Florida, United States
| | - Y. Liu
- Translational Research Institute, AdventHealth, Orlando, Florida, United States
| | - K. Corbin
- Translational Research Institute, AdventHealth, Orlando, Florida, United States
| | | | - K. Ruud
- MEI Research, Ltd., Edina, Minnesota, United States
| | - J. Moon
- MEI Research, Ltd., Edina, Minnesota, United States
| | - A. Marcus
- Biodesign Swette Center for Environmental Biotechnology, Arizona State University, Tempe, Arizona, United States
- Biodesign Center for Health Through Microbiomes, Arizona State University, Tempe, Arizona, United States
| | - R. Krajmalnik-Brown
- Biodesign Center for Health Through Microbiomes, Arizona State University, Tempe, Arizona, United States
| | - A. Muraviev
- CREOL, College of Optics and Photonics, University of Central Florida, Orlando, Florida, United States
| | - K. L. Vodopyanov
- CREOL, College of Optics and Photonics, University of Central Florida, Orlando, Florida, United States
| | - S. R. Smith
- Translational Research Institute, AdventHealth, Orlando, Florida, United States
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15
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Aja-Cadena MG, Amieva-Balmori M, Taboada-Liceaga HA, Cobos-Quevedo OJ, Hernández-Ramírez GA, Reyes-Huerta J, Roesch-Dietlen F, Meixuerio-Daza A, Remes-Troche JM. Prevalence of methanogens and associated factors in patients with irritable bowel syndrome and healthy controls in a Southeastern Mexican population. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2023; 88:50-56. [PMID: 34863643 DOI: 10.1016/j.rgmxen.2021.11.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 04/30/2021] [Indexed: 11/16/2022]
Abstract
INTRODUCTION Methane (CH4) is an inert gas produced by colonic anaerobes and has been associated with different intestinal diseases, including irritable bowel syndrome (IBS). According to geographic region, the prevalence of methanogens varies, being higher in Africa (80%) and lower in the United States (35-40%). In Mexico, the prevalence of methanogens is unknown. AIM To evaluate the prevalence of CH4 producers and associated factors in a group of patients with IBS and controls in a Mexican population. MATERIALS AND METHODS A baseline fasting measurement of alveolar H2 and CH4 gas was carried out, by gas chromatography (stationary phase), in consecutive patients diagnosed with IBS and a control group. Subjects with baseline levels of H2 of 0 ppm and CH4 ≥ 5 ppm were classified as methanogenic. RESULTS A total of 132 controls (53.8% women) and 67 patients with IBS (76% women) were included. The overall prevalence (n = 199) of methanogenic subjects was 38% (n = 76) (95% CI: 0.31-0.45) and they had a greater prevalence of overweight/obesity (56.5 vs 39.8%, P = .028). The prevalence of methanogens in the healthy controls was 41.6% (95% CI: 0.33-0.49), whereas, in the patients with IBS, it was 31.4% (n = 21, 71% IBS-C and 29% IBS-M). CONCLUSIONS The prevalence of methanogens in our study on a Mexican population was comparable to that reported in other populations and was associated with overweight/obesity. One-third of the patients with IBS presented with methanogens. Said microorganisms were particularlyassociated with the constipation-predominant IBS subtype.
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Affiliation(s)
- M G Aja-Cadena
- Laboratorio de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Médico Biológicas, Universidad Veracruzana, Veracruz, Veracruz, Veracruz, Mexico
| | - M Amieva-Balmori
- Laboratorio de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Médico Biológicas, Universidad Veracruzana, Veracruz, Veracruz, Veracruz, Mexico
| | - H A Taboada-Liceaga
- Laboratorio de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Médico Biológicas, Universidad Veracruzana, Veracruz, Veracruz, Veracruz, Mexico
| | - O J Cobos-Quevedo
- Laboratorio de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Médico Biológicas, Universidad Veracruzana, Veracruz, Veracruz, Veracruz, Mexico
| | - G A Hernández-Ramírez
- Laboratorio de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Médico Biológicas, Universidad Veracruzana, Veracruz, Veracruz, Veracruz, Mexico
| | - J Reyes-Huerta
- Laboratorio de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Médico Biológicas, Universidad Veracruzana, Veracruz, Veracruz, Veracruz, Mexico
| | - F Roesch-Dietlen
- Laboratorio de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Médico Biológicas, Universidad Veracruzana, Veracruz, Veracruz, Veracruz, Mexico
| | - A Meixuerio-Daza
- Laboratorio de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Médico Biológicas, Universidad Veracruzana, Veracruz, Veracruz, Veracruz, Mexico
| | - J M Remes-Troche
- Laboratorio de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Médico Biológicas, Universidad Veracruzana, Veracruz, Veracruz, Veracruz, Mexico.
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16
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Wang T, van Dijk L, Rijnaarts I, Hermes GDA, de Roos NM, Witteman BJM, de Wit NJW, Govers C, Smidt H, Zoetendal EG. Methanogen Levels Are Significantly Associated with Fecal Microbiota Composition and Alpha Diversity in Healthy Adults and Irritable Bowel Syndrome Patients. Microbiol Spectr 2022; 10:e0165322. [PMID: 36321894 PMCID: PMC9769613 DOI: 10.1128/spectrum.01653-22] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Accepted: 10/14/2022] [Indexed: 11/07/2022] Open
Abstract
Hydrogenotrophic microbes, primarily including the three functional groups methanogens, sulfate-reducing bacteria, and reductive acetogens, use hydrogen as an energy source and play an important role in maintaining the hydrogen balance in gut ecosystems. A distorted hydrogen balance has been associated with irritable bowel syndrome (IBS). However, the role of hydrogenotrophic microbes in overall microbiota composition and function remains largely unknown. This study aims to assess the distribution and stability of hydrogenotrophic functional groups in healthy adults (HAs) and IBS patients and their association with overall microbiota composition and IBS symptoms. A two-time-point study with 4 weeks in between was performed with 27 HAs and 55 IBS patients included. Our observations revealed that methanogens showed a bimodal distribution across samples. A high-level methanogen microbiota was consistently associated with higher alpha diversity, and its composition was significantly different from that of individuals with a low-level methanogen microbiota. In general, these associations were more pronounced in IBS patients than in HAs. The differences in the copy numbers of genes indicative of total bacteria and acetogens between HAs and IBS patients and their correlations with IBS symptom severity, anxiety, depression, and quality of life (QoL) were sampling time dependent. Hydrogenotrophic functional groups did not show negative abundance correlations with each other in HAs and IBS patients. These findings suggest that methanogen levels in the gut have a pronounced association with microbiota alpha diversity and composition, and the interactions between hydrogenotrophic functional groups are complex in gut ecosystems. IMPORTANCE Hydrogenotrophic microbes play an essential role in the disposal of hydrogen and the maintenance of the hydrogen balance in gut ecosystems. Their abundances vary between individuals and have been reported to be associated with human gut disorders such as irritable bowel disease. This study confirms that methanogen levels show a bimodal distribution. Moreover, a high-level methanogen microbiota was associated with higher alpha diversity, and its composition was different from that of individuals with a low-level methanogen microbiota. These associations are more pronounced in IBS patients than in healthy subjects. In addition, associations between hydrogenotrophic microbes and IBS symptom scores vary over time, which argues for the use of longitudinal study designs. Last but not least, this study suggests that the different hydrogenotrophic microbes coexist with each other and do not necessarily compete for hydrogen in the gut. The findings in this study highlight the impact of methanogens on overall microbiota composition and function.
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Affiliation(s)
- Taojun Wang
- Laboratory of Microbiology, Wageningen University and Research, Wageningen, the Netherlands
| | - Leander van Dijk
- Laboratory of Microbiology, Wageningen University and Research, Wageningen, the Netherlands
| | - Iris Rijnaarts
- Laboratory of Microbiology, Wageningen University and Research, Wageningen, the Netherlands
- Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, the Netherlands
- Wageningen Food and Biobased Research, Wageningen University and Research, Wageningen, the Netherlands
| | - Gerben D. A. Hermes
- Laboratory of Microbiology, Wageningen University and Research, Wageningen, the Netherlands
| | - Nicole M. de Roos
- Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, the Netherlands
| | - Ben J. M. Witteman
- Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, the Netherlands
- Department of Gastroenterology and Hepatology, Hospital Gelderse Vallei, Ede, the Netherlands
| | - Nicole J. W. de Wit
- Wageningen Food and Biobased Research, Wageningen University and Research, Wageningen, the Netherlands
| | - Coen Govers
- Wageningen Food and Biobased Research, Wageningen University and Research, Wageningen, the Netherlands
- Cell Biology and Immunology, Wageningen University and Research, Wageningen, the Netherlands
| | - Hauke Smidt
- Laboratory of Microbiology, Wageningen University and Research, Wageningen, the Netherlands
| | - Erwin G. Zoetendal
- Laboratory of Microbiology, Wageningen University and Research, Wageningen, the Netherlands
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17
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Liu A, Gao W, Zhu Y, Hou X, Chu H. Gut Non-Bacterial Microbiota: Emerging Link to Irritable Bowel Syndrome. Toxins (Basel) 2022; 14:596. [PMID: 36136534 PMCID: PMC9503233 DOI: 10.3390/toxins14090596] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 08/18/2022] [Accepted: 08/25/2022] [Indexed: 11/20/2022] Open
Abstract
As a common functional gastrointestinal disorder, irritable bowel syndrome (IBS) significantly affects personal health and imposes a substantial economic burden on society, but the current understanding of its occurrence and treatment is still inadequate. Emerging evidence suggests that IBS is associated with gut microbial dysbiosis, but most studies focus on the bacteria and neglect other communities of the microbiota, including fungi, viruses, archaea, and other parasitic microorganisms. This review summarizes the latest findings that link the nonbacterial microbiota with IBS. IBS patients show less fungal and viral diversity but some alterations in mycobiome, virome, and archaeome, such as an increased abundance of Candida albicans. Moreover, fungi and methanogens can aid in diagnosis. Fungi are related to distinct IBS symptoms and induce immune responses, intestinal barrier disruption, and visceral hypersensitivity via specific receptors, cells, and metabolites. Novel therapeutic methods for IBS include fungicides, inhibitors targeting fungal pathogenic pathways, probiotic fungi, prebiotics, and fecal microbiota transplantation. Additionally, viruses, methanogens, and parasitic microorganisms are also involved in the pathophysiology and treatment. Therefore, the gut nonbacterial microbiota is involved in the pathogenesis of IBS, which provides a novel perspective on the noninvasive diagnosis and precise treatment of this disease.
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Affiliation(s)
- Ao Liu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China
| | - Wenkang Gao
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China
| | - Yixin Zhu
- Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA
| | - Xiaohua Hou
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China
| | - Huikuan Chu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China
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18
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Li M, Bekö G, Zannoni N, Pugliese G, Carrito M, Cera N, Moura C, Wargocki P, Vasconcelos P, Nobre P, Wang N, Ernle L, Williams J. Human metabolic emissions of carbon dioxide and methane and their implications for carbon emissions. THE SCIENCE OF THE TOTAL ENVIRONMENT 2022; 833:155241. [PMID: 35421492 DOI: 10.1016/j.scitotenv.2022.155241] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Revised: 04/04/2022] [Accepted: 04/08/2022] [Indexed: 06/14/2023]
Abstract
Carbon dioxide (CO2) and methane (CH4) are important greenhouse gases in the atmosphere and have large impacts on Earth's radiative forcing and climate. Their natural and anthropogenic emissions have often been in focus, while the role of human metabolic emissions has received less attention. In this study, exhaled, dermal and whole-body CO2 and CH4 emission rates from a total of 20 volunteers were quantified under various controlled environmental conditions in a climate chamber. The whole-body CO2 emissions increased with temperature. Individual differences were the most important factor for the whole-body CH4 emissions. Dermal emissions of CO2 and CH4 only contributed ~3.5% and ~5.5% to the whole-body emissions, respectively. Breath measurements conducted on 24 volunteers in a companion study identified one third of the volunteers as CH4 producers (exhaled CH4 exceeded 1 ppm above ambient level). The exhaled CH4 emission rate of these CH4 producers (4.03 ± 0.71 mg/h/person, mean ± one standard deviation) was ten times higher than that of the rest of the volunteers (non-CH4 producers; 0.41 ± 0.45 mg/h/person). With increasing global population and the expected large reduction in global anthropogenic carbon emissions in the next decades, metabolic emissions of CH4 (although not CO2) from humans may play an increasing role in regional and global carbon budgets.
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Affiliation(s)
- Mengze Li
- Max Planck Institute for Chemistry, Hahn-Meitner-Weg 1, 55128 Mainz, Germany; Department of Climate and Space Sciences and Engineering, University of Michigan, Ann Arbor, USA.
| | - Gabriel Bekö
- International Centre for Indoor Environment and Energy, Department of Civil Engineering, Technical University of Denmark, Lyngby 2800, Denmark; Department of Architecture, College of Architecture, Art and Design, Ajman University, Ajman, P.O. Box 346, United Arab Emirates
| | - Nora Zannoni
- Max Planck Institute for Chemistry, Hahn-Meitner-Weg 1, 55128 Mainz, Germany
| | - Giovanni Pugliese
- Max Planck Institute for Chemistry, Hahn-Meitner-Weg 1, 55128 Mainz, Germany; Department of Anaesthesia and Intensive Care, Rostock University Medical Center, Schillingallee 35, 18057 Rostock, Germany
| | - Mariana Carrito
- Center for Psychology at University of Porto (CPUP), Faculty of Psychology and Education Sciences, University of Porto, Porto, Portugal
| | - Nicoletta Cera
- Center for Psychology at University of Porto (CPUP), Faculty of Psychology and Education Sciences, University of Porto, Porto, Portugal; Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), Coimbra, Portugal
| | - Catarina Moura
- Center for Psychology at University of Porto (CPUP), Faculty of Psychology and Education Sciences, University of Porto, Porto, Portugal
| | - Pawel Wargocki
- International Centre for Indoor Environment and Energy, Department of Civil Engineering, Technical University of Denmark, Lyngby 2800, Denmark
| | - Priscila Vasconcelos
- Center for Psychology at University of Porto (CPUP), Faculty of Psychology and Education Sciences, University of Porto, Porto, Portugal
| | - Pedro Nobre
- Center for Psychology at University of Porto (CPUP), Faculty of Psychology and Education Sciences, University of Porto, Porto, Portugal
| | - Nijing Wang
- Max Planck Institute for Chemistry, Hahn-Meitner-Weg 1, 55128 Mainz, Germany
| | - Lisa Ernle
- Max Planck Institute for Chemistry, Hahn-Meitner-Weg 1, 55128 Mainz, Germany
| | - Jonathan Williams
- Max Planck Institute for Chemistry, Hahn-Meitner-Weg 1, 55128 Mainz, Germany.
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Alegre E, Sandúa A, Calleja S, Deza S, González Á. Modification of baseline status to improve breath tests performance. Sci Rep 2022; 12:9752. [PMID: 35697832 PMCID: PMC9192647 DOI: 10.1038/s41598-022-14210-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Accepted: 06/02/2022] [Indexed: 11/20/2022] Open
Abstract
Breath tests used to evaluate carbohydrates malabsorption require baseline H2 and CH4 levels as low as possible. Test cancellation is recommended when exceeding certain cut-offs (H2 ≥ 20 ppm and CH4 ≥ 10 ppm). Although following preparation protocols, many patients have baseline levels above those cut-offs. We investigated if light walking can reduce baseline H2 and CH4 levels. We retrospectively analyzed baseline H2 and CH4 levels from 1552 breath tests. Baseline levels (B1), especially in H2, were lower when obtained at later hours of the day. In those with baseline levels above cut-off, re-sampling (B2) after light walking for one hour, decreased H2 levels 8 ppm (Q1-Q3: 1-18 ppm), and 2 ppm (Q1-Q3: 0-3 ppm) for CH4. Consequently, 40% of tests with elevated B1 levels, presented B2 levels below mentioned cut-offs. Ten percent of tests considered negative when using B1 for calculations, turned positive when using B2 instead. All positive tests when using B1 values, remained elevated when using B2. Re-sampling after light walking for one hour could allow test performance in those with previous elevated baseline levels, avoiding diagnosis delays. Using the second sample for delta calculations identifies positive patients for malabsorption that would have been considered negative.
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Affiliation(s)
- Estibaliz Alegre
- Clínica Universidad de Navarra (Service of Biochemistry), Av. Pío XII 36, 31008, Pamplona, Spain.
- IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
| | - Amaia Sandúa
- Clínica Universidad de Navarra (Service of Biochemistry), Av. Pío XII 36, 31008, Pamplona, Spain
| | - Sofía Calleja
- Clínica Universidad de Navarra (Service of Biochemistry), Av. Pío XII 36, 31008, Pamplona, Spain
| | - Sara Deza
- Clínica Universidad de Navarra (Service of Biochemistry), Av. Pío XII 36, 31008, Pamplona, Spain
| | - Álvaro González
- Clínica Universidad de Navarra (Service of Biochemistry), Av. Pío XII 36, 31008, Pamplona, Spain
- IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
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20
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Shah A, Talley NJ, Holtmann G. Current and Future Approaches for Diagnosing Small Intestinal Dysbiosis in Patients With Symptoms of Functional Dyspepsia. Front Neurosci 2022; 16:830356. [PMID: 35600619 PMCID: PMC9121133 DOI: 10.3389/fnins.2022.830356] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 03/28/2022] [Indexed: 12/12/2022] Open
Abstract
The development and application of next generation sequencing technologies for clinical gastroenterology research has provided evidence that microbial dysbiosis is of relevance for the pathogenesis of gastrointestinal and extra-intestinal diseases. Microbial dysbiosis is characterized as alterations of diversity, function, and density of the intestinal microbes. Emerging evidence suggests that alterations of the gastrointestinal microbiome are important for the pathophysiology of a variety of functional gastrointestinal conditions, e.g., irritable bowel syndrome (IBS) and functional dyspepsia (FD), also known as disorders of brain-gut axis interaction. Clinicians have for many years recognized that small intestinal bacterial overgrowth (SIBO) is typified by a microbial dysbiosis that is underpinned by abnormal bacterial loads in these sites. SIBO presents with symptoms which overlap with symptoms of FD and IBS, point toward the possibility that SIBO is either the cause or the consequence of functional gastrointestinal disorders (FGIDs). More recently, new terms including "intestinal methanogen overgrowth" and "small intestinal fungal overgrowth" have been introduced to emphasize the contribution of methane production by archea and fungi in small intestinal dysbiosis. There is emerging data that targeted antimicrobial treatment of SIBO in patients with FD who simultaneously may or may not have IBS, results in symptom improvement and normalization of positive breath tests. However, the association between SIBO and FGIDs remains controversial, since widely accepted diagnostic tests for SIBO are lacking. Culture of jejunal fluid aspirate has been proposed as the "traditional gold standard" for establishing the diagnosis of SIBO. Utilizing jejunal fluid culture, the results can potentially be affected by cross contamination from oropharyngeal and luminal microbes, and there is controversy regarding the best cut off values for SIBO diagnosis. Thus, it is rarely used in routine clinical settings. These limitations have led to the development of breath tests, which when compared with the "traditional gold standard," have sub-optimal sensitivity and specificity for SIBO diagnosis. With newer diagnostic approaches-based upon applications of the molecular techniques there is an opportunity to characterize the duodenal and colonic mucosa associated microbiome and associated gut microbiota dysbiosis in patients with various gastrointestinal and extraintestinal diseases. Furthermore, the role of confounders like psychological co-morbidities, medications, dietary practices, and environmental factors on the gastrointestinal microbiome in health and disease also needs to be explored.
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Affiliation(s)
- Ayesha Shah
- Faculty of Medicine and Faculty of Health and Behavioural Sciences, The University of Queensland, Brisbane, QLD, Australia
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, QLD, Australia
- AGIRA (Australian Gastrointestinal Research Alliance) and the NHMRC Centre of Research Excellence in Digestive Health, Newcastle, NSW, Australia
| | - Nicholas J. Talley
- AGIRA (Australian Gastrointestinal Research Alliance) and the NHMRC Centre of Research Excellence in Digestive Health, Newcastle, NSW, Australia
- College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW, Australia
| | - Gerald Holtmann
- Faculty of Medicine and Faculty of Health and Behavioural Sciences, The University of Queensland, Brisbane, QLD, Australia
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, QLD, Australia
- AGIRA (Australian Gastrointestinal Research Alliance) and the NHMRC Centre of Research Excellence in Digestive Health, Newcastle, NSW, Australia
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21
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Gunn D, Abbas Z, Harris HC, Major G, Hoad C, Gowland P, Marciani L, Gill SK, Warren FJ, Rossi M, Remes-Troche JM, Whelan K, Spiller RC. Psyllium reduces inulin-induced colonic gas production in IBS: MRI and in vitro fermentation studies. Gut 2022; 71:919-927. [PMID: 34353864 PMCID: PMC8995815 DOI: 10.1136/gutjnl-2021-324784] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Accepted: 07/08/2021] [Indexed: 12/14/2022]
Abstract
OBJECTIVE Health-promoting dietary fibre including inulin often triggers gastrointestinal symptoms in patients with IBS, limiting their intake. Our aim was to test if coadministering psyllium with inulin would reduce gas production. DESIGN A randomised, four-period, four-treatment, placebo-controlled, crossover trial in 19 patients with IBS. Subjects ingested a 500 mL test drink containing either inulin 20 g, psyllium 20 g, inulin 20 g+ psyllium 20 g or dextrose 20 g (placebo). Breath hydrogen was measured every 30 min with MRI scans hourly for 6 hours. Faecal samples from a subset of the patients with IBS were tested using an in vitro fermentation model. Primary endpoint was colonic gas assessed by MRI. RESULTS Colonic gas rose steadily from 0 to 6 hours, with inulin causing the greatest rise, median (IQR) AUC(0-360 min) 3145 (848-6502) mL·min. This was significantly reduced with inulin and psyllium coadministration to 618 (62-2345) mL·min (p=0.02), not significantly different from placebo. Colonic volumes AUC(0-360 min) were significantly larger than placebo for both inulin (p=0.002) and inulin and psyllium coadministration (p=0.005). Breath hydrogen rose significantly from 120 min after inulin but not psyllium; coadministration of psyllium with inulin delayed and reduced the maximum increase, AUC(0-360 min) from 7230 (3255-17910) ppm·hour to 1035 (360-4320) ppm·hour, p=0.007.Fermentation in vitro produced more gas with inulin than psyllium. Combining psyllium with inulin did not reduce gas production. CONCLUSIONS Psyllium reduced inulin-related gas production in patients with IBS but does not directly inhibit fermentation. Whether coadministration with psyllium increases the tolerability of prebiotics in IBS warrants further study. TRIAL REGISTRATION NUMBER NCT03265002.
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Affiliation(s)
- David Gunn
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK
| | - Zainab Abbas
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK
| | - Hannah C Harris
- Food, Innovation and Health, Quadram Institute Bioscience, Norwich, UK
| | - Giles Major
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK
| | - Caroline Hoad
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK
| | - Penny Gowland
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK
| | - Luca Marciani
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK
| | - Samantha K Gill
- Department of Nutritional Sciences, King's College London, London, UK
| | - Fred J Warren
- Food, Innovation and Health, Quadram Institute Bioscience, Norwich, UK
| | - Megan Rossi
- Department of Nutritional Sciences, King's College London, London, UK
| | | | - Kevin Whelan
- Department of Nutritional Sciences, King's College London, London, UK
| | - Robin C Spiller
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK
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22
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Shah A, Holtmann G. Small intestinal bacterial overgrowth in inflammatory bowel disease. Indian J Gastroenterol 2022; 41:23-29. [PMID: 35031976 DOI: 10.1007/s12664-021-01235-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 12/06/2021] [Indexed: 02/04/2023]
Affiliation(s)
- Ayesha Shah
- Faculty of Medicine and Faculty of Health and Behavioral Sciences, The University of Queensland, Brisbane, Australia. .,Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia. .,AGIRA (Australian Gastrointestinal Research Alliance) and the NHMRC Centre of Research Excellence in Digestive Health, Brisbane, Australia.
| | - Gerald Holtmann
- Faculty of Medicine and Faculty of Health and Behavioral Sciences, The University of Queensland, Brisbane, Australia.,Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia.,AGIRA (Australian Gastrointestinal Research Alliance) and the NHMRC Centre of Research Excellence in Digestive Health, Brisbane, Australia
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23
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Gandhi A, Shah A, Jones MP, Koloski N, Talley NJ, Morrison M, Holtmann G. Methane positive small intestinal bacterial overgrowth in inflammatory bowel disease and irritable bowel syndrome: A systematic review and meta-analysis. Gut Microbes 2022; 13:1933313. [PMID: 34190027 PMCID: PMC8253120 DOI: 10.1080/19490976.2021.1933313] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Several studies reported a potential role of methane producing archaea in the pathophysiology of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). We conducted a systematic review and meta-analysis to assess the prevalence of methane positive small intestinal bacterial overgrowth (SIBO) in IBS and IBD compared with controls. MEDLINE (PubMed) and Embase electronic databases were searched from inception until March 2021 for case-control and prevalence studies reporting SIBO in IBS and IBD. We extracted data from published studies and calculated pooled prevalence of SIBO in IBS or IBD, odds ratios (OR), and 95% CIs, utilizing a random effects model. The final dataset included 17 independent studies assessing the prevalence of methane positive SIBO in 1,653 IBS-patients and 713 controls, and 7 studies assessing the prevalence of methane positive SIBO in 626 IBD-patients and 497 controls, all utilizing breath test for SIBO diagnosis. Prevalence of methane positive SIBO in IBS and IBD was 25.0% (95% CI 18.8-32.4) and 5.6% (95% CI 2.6-11.8), respectively. Methane positive SIBO in IBS was not increased compared to controls (OR = 1.2, 95% CI 0.8-1.7, P = .37) but was significantly more prevalent in IBS-C as compared to IBS-D (OR = 3.1, 95% CI 1.7-5.6, P = .0001). The prevalence of methane-positive SIBO in patients with IBD was 3-fold lower at 7.4% (95% CI 5.4-9.8) compared to 23.5% (95% CI 19.8-27.5) in controls. The prevalence of methane positive SIBO was significantly lower in Crohn's disease as compared to ulcerative colitis, (5.3%, 95% CI 3.0-8.5 vs. 20.2%, 95% CI 12.8-29.4). This systematic review and meta-analysis suggests methane positivity on breath testing is positively associated with IBS-C and inversely with IBD. However, the quality of evidence is low largely due to clinical heterogeneity of the studies. Thus, causality is uncertain and further studies are required.
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Affiliation(s)
- Arjun Gandhi
- Faculty of Medicine, The University of Queensland, Queensland, Australia,Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia
| | - Ayesha Shah
- Faculty of Medicine, The University of Queensland, Queensland, Australia,Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia,Translational Research Institute, Brisbane, Queensland, Australia
| | - Michael P. Jones
- Department of Psychology, Macquarie University, Sydney, New South Wales, Australia
| | - Natasha Koloski
- Faculty of Medicine, The University of Queensland, Queensland, Australia,Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia,Translational Research Institute, Brisbane, Queensland, Australia
| | - Nicholas J. Talley
- Faculty of Health and Medicine, The University of Newcastle, Newcastle, Australia
| | - Mark Morrison
- Faculty of Medicine, The University of Queensland, Queensland, Australia,Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia,University of Queensland, Diamantina Institute, Brisbane, Queensland, Australia
| | - Gerald Holtmann
- Faculty of Medicine, The University of Queensland, Queensland, Australia,Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia,Translational Research Institute, Brisbane, Queensland, Australia,CONTACT Gerald Holtmann Brisbane Department of Gastroenterology and Hepatology & University of Queensland Ipswich Road, Woolloongabba, Queensland, Australia
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24
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Broekaert IJ, Borrelli O, Dolinsek J, Martin-de-Carpi J, Mas E, Miele E, Pienar C, Ribes-Koninckx C, Thomassen R, Thomson M, Tzivinikos C, Benninga M. An ESPGHAN Position Paper on the Use of Breath Testing in Paediatric Gastroenterology. J Pediatr Gastroenterol Nutr 2022; 74:123-137. [PMID: 34292218 DOI: 10.1097/mpg.0000000000003245] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
OBJECTIVES Given a lack of a systematic approach to the use of breath testing in paediatric patients, the aim of this position paper is to provide expert guidance regarding the indications for its use and practical considerations to optimise its utility and safety. METHODS Nine clinical questions regarding methodology, interpretation, and specific indications of breath testing and treatment of carbohydrate malabsorption were addressed by members of the Gastroenterology Committee (GIC) of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN).A systematic literature search was performed from 1983 to 2020 using PubMed, the MEDLINE and Cochrane Database of Systematic Reviews. Grading of Recommendations, Assessment, Development, and Evaluation was applied to evaluate the outcomes.During a consensus meeting, all recommendations were discussed and finalised. In the absence of evidence from randomised controlled trials, recommendations reflect the expert opinion of the authors. RESULTS A total of 22 recommendations were voted on using the nominal voting technique. At first, recommendations on prerequisites and preparation for as well as on interpretation of breath tests are given. Then, recommendations on the usefulness of H2-lactose breath testing, H2-fructose breath testing as well as of breath tests for other types of carbohydrate malabsorption are provided. Furthermore, breath testing is recommended to diagnose small intestinal bacterial overgrowth (SIBO), to control for success of Helicobacter pylori eradication therapy and to diagnose and monitor therapy of exocrine pancreatic insufficiency, but not to estimate oro-caecal transit time (OCTT) or to diagnose and follow-up on celiac disease. CONCLUSIONS Breath tests are frequently used in paediatric gastroenterology mainly assessing carbohydrate malabsorption, but also in the diagnosis of small intestinal overgrowth, fat malabsorption, H. pylori infection as well as for measuring gastrointestinal transit times. Interpretation of the results can be challenging and in addition, pertinent symptoms should be considered to evaluate clinical tolerance.
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Affiliation(s)
- Ilse Julia Broekaert
- Department of Paediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Osvaldo Borrelli
- Department of Paediatric Gastroenterology, Great Ormond Street Hospital, London, UK
| | - Jernej Dolinsek
- Department of Paediatrics, University Medical Centre Maribor, Maribor, Slovenia
| | - Javier Martin-de-Carpi
- Department of Paediatric Gastroenterology, Hepatology and Nutrition, Hospital Sant Joan de Déu, Barcelona, Spain
| | - Emmanuel Mas
- Unité de Gastroentérologie, Hépatologie, Nutrition, Diabétologie et Maladies Héréditaires du Métabolisme, Hôpital des Enfants, CHU de Toulouse, Toulouse, France; IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France
| | - Erasmo Miele
- Department of Translational Medical Science, Section of Paediatrics, University of Naples "Federico", Naples, Italy
| | - Corina Pienar
- Department of Paediatrics, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Carmen Ribes-Koninckx
- Department of Paediatric Gastroenterology, Hepatology & Nutrition, La Fe University Hospital, Valencia, Spain
| | - Rut Thomassen
- Department of Paediatric Medicine, Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Norway
| | - Mike Thomson
- Centre for Paediatric Gastroenterology, Sheffield Children's Hospital, Sheffield, UK
| | - Christos Tzivinikos
- Department of Paediatric Gastroenterology, Al Jalila Children's Specialty Hospital, Dubai, UAE
| | - Marc Benninga
- Department of Paediatric Gastroenterology and Nutrition, Emma Children's Hospital, Amsterdam University Medical Centres, Amsterdam, The Netherlands
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25
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Back to the Source: Molecular Identification of Methanogenic Archaea as Markers of Colonic Methane Production. Dig Dis Sci 2021; 66:3661-3664. [PMID: 33469805 DOI: 10.1007/s10620-021-06839-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/08/2021] [Indexed: 12/09/2022]
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26
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Hydrogen and Methane Breath Test in the Diagnosis of Lactose Intolerance. Nutrients 2021; 13:nu13093261. [PMID: 34579138 PMCID: PMC8472045 DOI: 10.3390/nu13093261] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 08/29/2021] [Accepted: 09/15/2021] [Indexed: 12/31/2022] Open
Abstract
The hydrogen (H2) breath test is a non-invasive investigation used to diagnose lactose intolerance (LI). Patients with LI may also expire increased amounts of methane (CH4) during a lactose test. The aim of this study is to evaluate the contribution of CH4 measurements. We tested 209 children (1–17 years old) with symptoms suggesting LI with lactose H2 and CH4 breath tests. The result was positive when the H2 excretion exceeded 20 parts per million (ppm) and the CH4 was 10 ppm above the baseline. A clinician, blinded for the results of the breath test, registered the symptoms. Of the patient population, 101/209 (48%) were negative for both H2 and CH4; 96/209 (46%) had a positive H2 breath test result; 31/96 (32%) were also positive for CH4; 12/209 (6%) patients were only positive for CH4. The majority of hydrogen producers showed symptoms, whereas this was only the case in half of the H2-negative CH4 producers. Almost all patients treated with a lactose-poor diet reported significant symptom improvement. These results indicate that CH4 measurements may possibly be of additional value for the diagnosis of LI, since 5.7% of patients were negative for H2 and positive for CH4, and half of them experienced symptoms during the test.
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27
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Dębowski M, Korzeniewska E, Kazimierowicz J, Zieliński M. Efficiency of sweet whey fermentation with psychrophilic methanogens. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2021; 28:49314-49323. [PMID: 33934309 PMCID: PMC8410717 DOI: 10.1007/s11356-021-14095-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 04/20/2021] [Indexed: 06/12/2023]
Abstract
Sweet whey is a waste product from the dairy industry that is difficult to manage. High hopes are fostered regarding its neutralization in the methane fermentation. An economically viable alternative to a typical mesophilic fermentation seems to be the process involving psychrophilic bacteria isolated from the natural environment. This study aimed to determine the feasibility of exploiting psychrophilic microorganisms in methane fermentation of sweet whey. The experiments were carried out under dynamic conditions using Bio Flo 310 type flow-through anaerobic bioreactors. The temperature inside the reactors was 10 ± 1 °C. The HRT was 20 days and the OLR was 0.2 g COD/dm3/day. The study yielded 132.7 ± 13.8 mL biogas/gCODremoved. The CH4 concentration in the biogas was 32.7 ± 1.6%, that of H2 was 8.7 ± 4.7%, whereas that of CO2 reached 58.42 ± 2.47%. Other gases were also determined, though in lower concentrations. The COD and BOD5 removal efficiency reached 21.4 ± 0.6% and 17.6 ± 1.0%, respectively.
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Affiliation(s)
- Marcin Dębowski
- Department of Environment Engineering, Faculty of Geoengineering, University of Warmia and Mazury in Olsztyn, 10-720, Olsztyn, Poland
| | - Ewa Korzeniewska
- Department of Water Protection Engineering and Environmental Microbiology, Faculty of Geoengineering, University of Warmia and Mazury in Olsztyn, 10-720, Olsztyn, Poland
| | - Joanna Kazimierowicz
- Department of Water Supply and Sewage Systems, Faculty of Civil Engineering and Environmental Sciences, Bialystok University of Technology, 15-351, Bialystok, Poland.
| | - Marcin Zieliński
- Department of Environment Engineering, Faculty of Geoengineering, University of Warmia and Mazury in Olsztyn, 10-720, Olsztyn, Poland
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28
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Tomasova L, Grman M, Ondrias K, Ufnal M. The impact of gut microbiota metabolites on cellular bioenergetics and cardiometabolic health. Nutr Metab (Lond) 2021; 18:72. [PMID: 34266472 PMCID: PMC8281717 DOI: 10.1186/s12986-021-00598-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Accepted: 07/02/2021] [Indexed: 12/20/2022] Open
Abstract
Recent research demonstrates a reciprocal relationship between gut microbiota-derived metabolites and the host in controlling the energy homeostasis in mammals. On the one hand, to thrive, gut bacteria exploit nutrients digested by the host. On the other hand, the host utilizes numerous products of gut bacteria metabolism as a substrate for ATP production in the colon. Finally, bacterial metabolites seep from the gut into the bloodstream and interfere with the host’s cellular bioenergetics machinery. Notably, there is an association between alterations in microbiota composition and the development of metabolic diseases and their cardiovascular complications. Some metabolites, like short-chain fatty acids and trimethylamine, are considered markers of cardiometabolic health. Others, like hydrogen sulfide and nitrite, demonstrate antihypertensive properties. Scientific databases were searched for pre-clinical and clinical studies to summarize current knowledge on the role of gut microbiota metabolites in the regulation of mammalian bioenergetics and discuss their potential involvement in the development of cardiometabolic disorders. Overall, the available data demonstrates that gut bacteria products affect physiological and pathological processes controlling energy and vascular homeostasis. Thus, the modulation of microbiota-derived metabolites may represent a new approach for treating obesity, hypertension and type 2 diabetes.
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Affiliation(s)
- Lenka Tomasova
- Institute of Clinical and Translational Research, Biomedical Research Center, Slovak Academy of Sciences, Dubravska cesta 9, 845 05, Bratislava, Slovak Republic.
| | - Marian Grman
- Institute of Clinical and Translational Research, Biomedical Research Center, Slovak Academy of Sciences, Dubravska cesta 9, 845 05, Bratislava, Slovak Republic
| | - Karol Ondrias
- Institute of Clinical and Translational Research, Biomedical Research Center, Slovak Academy of Sciences, Dubravska cesta 9, 845 05, Bratislava, Slovak Republic
| | - Marcin Ufnal
- Department of Experimental Physiology and Pathophysiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, 02-091, Warsaw, Poland.
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29
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Shaker A, Peng B, Soffer E. Pattern of methane levels with lactulose breath testing; can we shorten the test duration? JGH Open 2021; 5:809-812. [PMID: 34263076 PMCID: PMC8264240 DOI: 10.1002/jgh3.12592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Revised: 04/23/2021] [Accepted: 06/06/2021] [Indexed: 11/23/2022]
Abstract
Background and Aim Methane levels in methane‐positive lactulose breath tests are frequently elevated at time zero. We hypothesized that baseline methane level is sufficient to detect excessive methane production and thereby avoid extended testing. Our aim was to determine if baseline methane levels were sufficient to identify methane‐positive individuals as defined by current guidelines. Methods A retrospective study of lactulose breath tests was conducted at an open access motility lab. A methane‐positive study was defined as a methane level ≥10 ppm at any time. Small intestinal bacterial overgrowth (SIBO) was defined as a ≥20 ppm rise in hydrogen from baseline by 90 min. Dual‐positive SIBO and methane studies were identified. Demographics, symptoms, and indications were recorded. Results Of 745 tests, 33.1%, 15.0%, and 3.1% were SIBO, methane, and dual‐positive, respectively. Precisely 96.4% of methane‐positive studies had methane levels ≥10 ppm within 90 min and 75.9% had levels ≥10 ppm at time 0. An additional elevation of ≥20 ppm over baseline within 90 min was observed in 32.1%. Of 22 methane‐positive patients with constipation, methane levels were ≥10 ppm at baseline in 81.8% and were ≥10 ppm within 90 min in all cases. Conclusions Nearly 25% of methane‐positive studies were not identified by a fasting methane level, but 96% were identified within 90 min. Most methane‐positive studies did not have a rise of 20 ppm above baseline. Our findings suggest the lactulose breath test for hydrogen and methane can be complete at 90 min.
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Affiliation(s)
- Anisa Shaker
- Department of Medicine Keck School of Medicine of University of Southern California Los Angeles California USA
| | - Billy Peng
- Department of Medicine Keck School of Medicine of University of Southern California Los Angeles California USA
| | - Edy Soffer
- Department of Medicine Keck School of Medicine of University of Southern California Los Angeles California USA
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Cortez APB, Fisberg M, de Morais MB. Intestinal permeability and small intestine bacterial overgrowth in excess weight adolescents. Pediatr Obes 2021; 16:e12741. [PMID: 33089672 DOI: 10.1111/ijpo.12741] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2020] [Revised: 08/21/2020] [Accepted: 09/28/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Increased intestinal permeability may be associated with certain disorders, such as obesity and small intestine bacterial overgrowth (SIBO). OBJECTIVE This study aimed to investigate intestinal permeability and SIBO in excess weight adolescents. METHODS This cross-sectional study included 67 adolescents with excess weight and 66 normal weight adolescents. Excess weight was defined as a body mass index for age (BMI/age) > +1 SD, which includes having excess body weight and obesity. SIBO was diagnosed by a breath test after the ingestion of lactulose according to the production of hydrogen and methane. Zonulin (haptoglobin) was considered an indicator of intestinal permeability. RESULTS Adolescents with excess weight had a higher height/age Z-score (median [25th; 75th percentile]: +0.6 [-0.4; +1.0]) than those in the normal weight group (-0.1 [-0.6; +0.7]; P = .014). Zonulin (mg/mL) in the excess weight (2.3 [1.5; 3.8]) adolescents was higher than that in the normal weight (1.6 [1.0; 2.2]) adolescents (P < .001). SIBO was diagnosed in 23.3% (31/133) of the adolescents. The adolescents with SIBO had a lower (P < .05) BMI/age (+0.6 [-0.6; +1.9]) and height/age (-0.3 [-0.7; +0.3]) than the adolescents without SIBO (+1.3 [+0.1; +2.6] and +0.2 [-0.5; +1.0], respectively). No association was found between zonulin and SIBO. CONCLUSION Excess weight is associated with increased intestinal permeability. No relationship was found between SIBO and intestinal permeability; however, SIBO was related to lower BMI and height for age Z-scores.
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Affiliation(s)
- Ana Paula Bidutte Cortez
- Post-Graduate Program in Nutrition, Federal University of São Paulo (Universidade Federal de São Paulo - UNIFESP), São Paulo, Brazil
| | - Mauro Fisberg
- Division of Pediatric Gastroenterology, Federal University of São Paulo (Universidade Federal de São Paulo - UNIFESP), São Paulo, Brazil.,Nutrition and Feeding Difficulties Center-Pensi Institute-Sabará Children's Hospital (Hospital Infantil Sabará), São Paulo, Brazil
| | - Mauro Batista de Morais
- Division of Pediatric Gastroenterology, Federal University of São Paulo (Universidade Federal de São Paulo - UNIFESP), São Paulo, Brazil
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How the North American Consensus Protocol Affects the Performance of Glucose Breath Testing for Bacterial Overgrowth Versus a Traditional Method. Am J Gastroenterol 2021; 116:780-787. [PMID: 33982948 DOI: 10.14309/ajg.0000000000001110] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION The North American Consensus guidelines for glucose breath testing (GBT) for small intestinal bacterial overgrowth (SIBO) incorporated changes in glucose dosing and diagnostic cutoffs. We compared GBT positivity based on hydrogen and methane excretion and quantified symptoms during performance of the North American vs older modified Rome Consensus protocols. METHODS GBT was performed using the North American protocol (75 g glucose, cutoffs >20 parts per million [ppm] hydrogen increase after glucose and >10 ppm methane anytime) in 3,102 patients vs modified Rome protocol (50 g glucose, >12 ppm hydrogen and methane increases after glucose) in 3,193 patients with suspected SIBO. RESULTS Positive GBT were more common with the North American vs modified Rome protocol (39.5% vs 29.7%, P < 0.001). Overall percentages with GBT positivity using methane criteria were greater and hydrogen criteria lower with the North American protocol (P < 0.001). Peak methane levels were higher for the North American protocol (P < 0.001). Times to peak hydrogen and methane production were not different between protocols. With the North American protocol, gastrointestinal and extraintestinal symptoms were more prevalent after glucose with both positive and negative GBT (P < 0.04) and greater numbers of symptoms (P < 0.001) were reported. DISCUSSION GBT performed using the North American Consensus protocol was more often positive for SIBO vs the modified Rome protocol because of more prevalent positive methane excretion. Symptoms during testing were greater with the North American protocol. Implications of these observations on determining breath test positivity and antibiotic decisions for SIBO await future prospective testing.
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Hammer K, Hasanagic H, Memaran N, Huber WD, Hammer J. Relevance of Methane and Carbon Dioxide Evaluation in Breath Tests for Carbohydrate Malabsorption in a Paediatric Cohort. J Pediatr Gastroenterol Nutr 2021; 72:e71-e77. [PMID: 33560761 DOI: 10.1097/mpg.0000000000003004] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
OBJECTIVES The relevance of methane measurement in breath tests for the detection of carbohydrate malabsorption in children is controversial. The need for correction for poor sample collection is disputed. We evaluated the relevance of methane/CO2 measurements for the diagnosis of paediatric carbohydrate malabsorption. METHODS A total of 132 breath tests (fructose: n = 54; lactose: n = 78) were performed in 91 children/adolescents with functional abdominal complaints. Breath samples were collected and analysed for hydrogen, methane, and CO2. Malabsorption was defined by a net increase over baseline of ≥20 parts per million (ppm) for hydrogen, ≥5 to ≥12 ppm for methane, and ≥10 to ≥15 ppm for hydrogen-plus-methane. The diagnosis was made before and after the use of a CO2-based correction factor (5.5% as the numerator). Hydrogen-based test results were compared with results obtained with other cut-off values. RESULTS Fifty-eight positive tests were obtained by hydrogen measurement (without CO2 correction). The addition of methane measurements did not significantly influence the test results (P > 0.05). Only under the use of extraordinary cut-offs (combined hydrogen-plus-methane smaller than ≥18 ppm) did the rate of malabsorbers increase significantly (P < 0.05). After CO2 correction, hydrogen ≥20 ppm was detected in 4 additional patients, but 1 patient lost the hydrogen-based diagnosis of malabsorption (Cohen kappa = 0.92). CONCLUSIONS Methane measurement did not significantly affect the detection rate of carbohydrate malabsorbers in children/adolescents with functional abdominal complaints when established cut-offs are used. The use of CO2 correction altered the diagnosis of malabsorption in a minority of patients but did not significantly alter overall test results.
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Affiliation(s)
| | - Hana Hasanagic
- Abteilung für Gastroenterologie und Hepatologie, Universitätsklinik für Innere Medizin 3; Medical University of Vienna, Austria
| | - Nima Memaran
- Department of Paediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hanover, Germany
| | - Wolf-Dietrich Huber
- Klinische Abteilung für Pädiatrische Nephrologie und Gastroenterologie, Universitätsklinik für Kinder- und Jugendheilkunde, Medical University of Vienna, Austria
| | - Johann Hammer
- Abteilung für Gastroenterologie und Hepatologie, Universitätsklinik für Innere Medizin 3; Medical University of Vienna, Austria
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Bársony A, Vida N, Gajda Á, Rutai A, Mohácsi Á, Szabó A, Boros M, Varga G, Érces D. Methane Exhalation Can Monitor the Microcirculatory Changes of the Intestinal Mucosa in a Large Animal Model of Hemorrhage and Fluid Resuscitation. Front Med (Lausanne) 2020; 7:567260. [PMID: 33195312 PMCID: PMC7642453 DOI: 10.3389/fmed.2020.567260] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 09/11/2020] [Indexed: 12/02/2022] Open
Abstract
Background: Internal hemorrhage is a medical emergency, which requires immediate causal therapy, but the recognition may be difficult. The reactive changes of the mesenteric circulation may be part of the earliest hemodynamic responses to bleeding. Methane is present in the luminal atmosphere; thus, we hypothesized that it can track the intestinal circulatory changes, induced by hemorrhage, non-invasively. Our goal was to validate and compare the sensitivity of this method with an established technique using sublingual microcirculatory monitoring in a large animal model of controlled, graded hemorrhage and the early phase of following fluid resuscitation. Materials and Methods: The experiments were performed on anesthetized, ventilated Vietnamese minipigs (approval number: V/148/2013; n = 6). The animals were gradually bled seven times consecutively of 5% of their estimated blood volume (BV) each, followed by gradual fluid resuscitation with colloid (hydroxyethyl starch; 5% of the estimated BV/dose) until 80 mmHg mean arterial pressure was achieved. After each step, macrohemodynamic parameters were recorded, and exhaled methane level was monitored continuously with a custom-built photoacoustic laser-spectroscopy unit. The microcirculation of the sublingual area, ileal serosa, and mucosa was examined by intravital videomicroscopy (Cytocam-IDF, Braedius). Results: Mesenteric perfusion was significantly reduced by a 5% blood loss, whereas microperfusion in the oral cavity deteriorated after a 25% loss. A statistically significant correlation was found between exhaled methane levels, superior mesenteric artery flow (r = 0.93), or microcirculatory changes in the ileal serosa (ρ = 0.78) and mucosa (r = 0.77). After resuscitation, the ileal mucosal microcirculation increased rapidly [De Backer score (DBS): 2.36 ± 0.42 vs. 8.6 ± 2.1 mm−1], whereas serosal perfusion changed gradually and with a lower amplitude (DBS: 2.51 ± 0.48 vs. 5.73 ± 0.75). Sublingual perfusion correlated with mucosal (r = 0.74) and serosal (r = 0.66) mesenteric microperfusion during the hemorrhage phase but not during the resuscitation phase. Conclusion: Detection of exhaled methane levels is of diagnostic significance during experimental hemorrhage as it indicates blood loss earlier than sublingual microcirculatory changes and in the early phase of fluid resuscitation, the exhaled methane values change in association with the mesenteric perfusion and the microcirculation of the ileum.
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Affiliation(s)
- Anett Bársony
- Department of Surgery, University of Szeged, Szeged, Hungary
| | - Noémi Vida
- Institute of Surgical Research, University of Szeged, Szeged, Hungary
| | - Ámos Gajda
- Institute of Surgical Research, University of Szeged, Szeged, Hungary
| | - Attila Rutai
- Institute of Surgical Research, University of Szeged, Szeged, Hungary
| | - Árpád Mohácsi
- MTA-SZTE Research Group on Photoacoustic Spectroscopy, Szeged, Hungary
| | - Anna Szabó
- Department of Optics and Quantum Electronics, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary
| | - Mihály Boros
- Institute of Surgical Research, University of Szeged, Szeged, Hungary
| | - Gabriella Varga
- Institute of Surgical Research, University of Szeged, Szeged, Hungary
| | - Dániel Érces
- Institute of Surgical Research, University of Szeged, Szeged, Hungary
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Abstract
Host-associated microbial communities have an important role in shaping the health and fitness of plants and animals. Most studies have focused on the bacterial, fungal or viral communities, but often the archaeal component has been neglected. The archaeal community, the so-called archaeome, is now increasingly recognized as an important component of host-associated microbiomes. It is composed of various lineages, including mainly Methanobacteriales and Methanomassiliicoccales (Euryarchaeota), as well as representatives of the Thaumarchaeota. Host-archaeome interactions have mostly been delineated from methanogenic archaea in the gastrointestinal tract, where they contribute to substantial methane production and are potentially also involved in disease-relevant processes. In this Review, we discuss the diversity and potential roles of the archaea associated with protists, plants and animals. We also present the current understanding of the archaeome in humans, the specific adaptations involved in interaction with the resident microbial community as well as with the host, and the roles of the archaeome in both health and disease.
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Dharmawardana N, Goddard T, Woods C, Watson DI, Butler R, Ooi EH, Yazbeck R. Breath methane to hydrogen ratio as a surrogate marker of intestinal dysbiosis in head and neck cancer. Sci Rep 2020; 10:15010. [PMID: 32929151 PMCID: PMC7490703 DOI: 10.1038/s41598-020-72115-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Accepted: 08/13/2020] [Indexed: 01/30/2023] Open
Abstract
Exhaled breath compounds can non-invasively detect head and neck squamous cell carcinoma (HNSCC). Here we investigated exhaled compounds related to intestinal bacterial carbohydrate fermentation. Fasting breath samples were collected into 3 litre FlexFoil PLUS bags from patients awaiting a biopsy procedure for suspected HNSCC. Samples were analysed using a Syft selected ion flow-tube mass spectrometer and a Quintron BreathTracker. Two tailed non-parametric significance testing was conducted with corrections for multiple imputations. 74 patients were diagnosed (histological) with HNSCC and 61 patients were benign (controls). The methane to hydrogen ratio was significantly different between cancer and non-cancer controls (p = 0.0440). This ratio increased with tumour stage with a significant difference between T1 and T4 tumours (p = 0.0259). Hydrogen levels were significantly higher in controls who were smokers (p = 0.0129), with no smoking dependent methane changes. There were no differences in short chain fatty acids between groups. Exhaled compounds of intestinal carbohydrate fermentation can detect HNSCC patients. These findings suggest a modified carbohydrate fermentation profile in HNSCC patients that is tumour stage and smoking status dependent.
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Affiliation(s)
- Nuwan Dharmawardana
- Department of Otorhinolaryngology-Head and Neck Surgery, Flinders Medical Centre, Bedford Park, Australia.
- Discipline of Surgery, College of Medicine and Public Health, Flinders University, Bedford Park, Australia.
| | - Thomas Goddard
- Department of Respiratory and Sleep Medicine, Women's and Children's Hospital, Adelaide, Australia
| | - Charmaine Woods
- Department of Otorhinolaryngology-Head and Neck Surgery, Flinders Medical Centre, Bedford Park, Australia
- Discipline of Surgery, College of Medicine and Public Health, Flinders University, Bedford Park, Australia
| | - David I Watson
- Discipline of Surgery, College of Medicine and Public Health, Flinders University, Bedford Park, Australia
| | - Ross Butler
- Discipline of Surgery, College of Medicine and Public Health, Flinders University, Bedford Park, Australia
| | - Eng H Ooi
- Department of Otorhinolaryngology-Head and Neck Surgery, Flinders Medical Centre, Bedford Park, Australia
- Discipline of Surgery, College of Medicine and Public Health, Flinders University, Bedford Park, Australia
| | - Roger Yazbeck
- Discipline of Surgery, College of Medicine and Public Health, Flinders University, Bedford Park, Australia
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Altered Gut Microbial Fermentation and Colonization with Methanobrevibacter smithii in Renal Transplant Recipients. J Clin Med 2020; 9:jcm9020518. [PMID: 32075113 PMCID: PMC7073595 DOI: 10.3390/jcm9020518] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Revised: 02/01/2020] [Accepted: 02/10/2020] [Indexed: 12/15/2022] Open
Abstract
Renal transplant recipients (RTRs) often suffer from posttransplant diarrhea. The observed dysbiosis in RTR may influence the fermentation processes in the gut. In this study, we aimed to investigate whether fermentation differs between RTRs and healthy controls (HCs), by measuring breath H2 and CH4 concentrations. Additionally, we determined the fecal presence of the methanogen Methanobrevibacter smithii (M. smithii), which plays a main role in the process of methanogenesis. Data from the TransplantLines Biobank and Cohort Study (NCT03272841) was used. A total of 142 RTRs and 77 HCs were included. Breath H2 concentrations in RTRs were not significantly different from HCs. Breath CH4 concentrations in RTRs were significantly lower compared with HCs (median [interquartile range (IQR)] 7.5 [3.9–10.6] ppm vs. 16.0 [8.0–45.5] ppm, p < 0.001). M. smithii was less frequently present in the feces of RTRs compared to HCs (28.6% vs. 86.4% resp., p < 0.001). Our findings regarding the altered methanogenesis in the gut of RTRs show similarities with previous results in inflammatory bowel disease patients. These findings provide novel insight into the alterations of fermentation after renal transplantation, which may contribute to understanding the occurrence of posttransplant diarrhea.
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Kim JW, Park SY, Chung JO, Cho HA, Kim DH, Yoon JH, Park CH, Kim HS, Choi SK, Rew JS. [Influencing Factors on Lactulose Breath Test Results]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2020; 75:23-28. [PMID: 31986570 DOI: 10.4166/kjg.2020.75.1.23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/07/2019] [Revised: 12/22/2019] [Accepted: 01/03/2019] [Indexed: 11/03/2022]
Abstract
BACKGROUND/AIMS This study aimed to identify the demographic and clinical factors associated with positive breath-test results and to assess the relationship between hydrogen and methane production in patients with suspected irritable bowel syndrome (IBS). METHODS The demographic and clinical factors of 268 patients with suspected IBS, who had undergone a lactulose breath test, were analyzed. RESULTS Of 268 patients included in this study, 143 (53.4%) were females. The median age and BMI of the patients was 58.0 years (range, 18.0-80.0 years) and 22.5 kg/m2 (range, 14.4-34.3 kg/m2), respectively. A weak positive correlation was observed between the BMI and baseline hydrogen level (rho=0.134, p=0.031). Women were significantly more likely to show a ≥20 ppm increase in hydrogen within 90 min (early hydrogen increase, p=0.049), a ≥10 ppm increase in methane within 90 min (early methane increase, p=0.001), and a ≥10 ppm increase in methane between 90 min and 180 min (late methane increase, p=0.002) compared to men. The baseline hydrogen level was related to the baseline methane level (rho=0.592, p<0.001) and the maximal hydrogen level within 90 min was related to maximal methane level within 90 min (rho=0.721, p<0.001). Patients with an early hydrogen increase (43.8%) were more likely to show a positive result for an early methane increase compared to patients without an early increase in hydrogen (0%, p<0.001). CONCLUSIONS Women were associated with high rates of positive lactulose breath-test results. In addition, methane production was correlated with hydrogen production.
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Affiliation(s)
- Jin Won Kim
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Seon-Young Park
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Jin Ook Chung
- Divisions of Gastroenterology and Endocrinology, Chonnam National University Medical School, Gwangju, Korea
| | - Hyun A Cho
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Dong-Hyun Kim
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Jae Hyun Yoon
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Chang Hwan Park
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Hyun Soo Kim
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Sung Kyu Choi
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Jong Sun Rew
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
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Poles MZ, Juhász L, Boros M. Methane and Inflammation - A Review (Fight Fire with Fire). Intensive Care Med Exp 2019; 7:68. [PMID: 31807906 PMCID: PMC6895343 DOI: 10.1186/s40635-019-0278-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Accepted: 10/24/2019] [Indexed: 12/23/2022] Open
Abstract
Mammalian methanogenesis is regarded as an indicator of carbohydrate fermentation by anaerobic gastrointestinal flora. Once generated by microbes or released by a non-bacterial process, methane is generally considered to be biologically inactive. However, recent studies have provided evidence for methane bioactivity in various in vivo settings. The administration of methane either in gas form or solutions has been shown to have anti-inflammatory and neuroprotective effects in an array of experimental conditions, such as ischemia/reperfusion, endotoxemia and sepsis. It has also been demonstrated that exogenous methane influences the key regulatory mechanisms and cellular signalling pathways involved in oxidative and nitrosative stress responses. This review offers an insight into the latest findings on the multi-faceted organ protective activity of exogenous methane treatments with special emphasis on its versatile effects demonstrated in sepsis models.
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Affiliation(s)
- Marietta Zita Poles
- Institute of Surgical Research, University of Szeged, Pulz u. 1., Szeged, H-6724, Hungary
| | - László Juhász
- Institute of Surgical Research, University of Szeged, Pulz u. 1., Szeged, H-6724, Hungary
| | - Mihály Boros
- Institute of Surgical Research, University of Szeged, Pulz u. 1., Szeged, H-6724, Hungary.
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Bui TPN, Schols HA, Jonathan M, Stams AJM, de Vos WM, Plugge CM. Mutual Metabolic Interactions in Co-cultures of the Intestinal Anaerostipes rhamnosivorans With an Acetogen, Methanogen, or Pectin-Degrader Affecting Butyrate Production. Front Microbiol 2019; 10:2449. [PMID: 31736896 PMCID: PMC6839446 DOI: 10.3389/fmicb.2019.02449] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Accepted: 10/11/2019] [Indexed: 12/31/2022] Open
Abstract
The human intestinal tract harbors diverse and complex microbial communities that have a vast metabolic capacity including the breakdown of complex carbohydrates into short chain fatty acids, acetate, propionate, and butyrate. As butyrate is beneficial for gut health there is much attention on butyrogenic bacteria and their role in the colonic anaerobic food chain. However, our understanding how production of butyrate by gut microorganisms is controlled by interactions between different species and environmental nutrient availability is very limited. To address this, we set up experimental in vitro co-culture systems to study the metabolic interactions of Anaerostipes rhamnosivorans, a butyrate producer with each of its partners; Blautia hydrogenotrophica, an acetogen; Methanobrevibacter smithii, a methanogen and Bacteroides thetaiotaomicron, a versatile degrader of plant cell wall pectins; through corresponding specific cross-feeding. In all co-cultures, A. rhamnosivorans was able to benefit from its partner for enhanced butyrate formation compared to monocultures. Interspecies transfer of hydrogen or formate from A. rhamnosivorans to the acetogen B. hydrogenotrophica and in turn of acetate from the acetogen to the butyrogen were essential for butyrate formation. A. rhamnosivorans grown on glucose supported growth of M. smithii via interspecies formate/hydrogen transfer enhancing butyrate formation. In the co-culture with pectin, lactate was released by B. thetaiotaomicron which was concomitantly used by A. rhamnosivorans for the production of butyrate. Our findings indicate enhanced butyrate formation through microbe-microbe interactions between A. rhamnosivorans and an acetogen, a methanogen or a pectin-degrader. Such microbial interactions enhancing butyrate formation may be beneficial for colonic health.
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Affiliation(s)
- Thi Phuong Nam Bui
- Laboratory of Microbiology, Wageningen University & Research, Wageningen, Netherlands
| | - Henk A Schols
- Laboratory of Food Chemistry, Wageningen University & Research, Wageningen, Netherlands
| | - Melliana Jonathan
- Laboratory of Food Chemistry, Wageningen University & Research, Wageningen, Netherlands
| | - Alfons J M Stams
- Laboratory of Microbiology, Wageningen University & Research, Wageningen, Netherlands
| | - Willem M de Vos
- Laboratory of Microbiology, Wageningen University & Research, Wageningen, Netherlands.,Human Microbiome Research Programme, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Caroline M Plugge
- Laboratory of Microbiology, Wageningen University & Research, Wageningen, Netherlands
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Boros M, Keppler F. Methane Production and Bioactivity-A Link to Oxido-Reductive Stress. Front Physiol 2019; 10:1244. [PMID: 31611816 PMCID: PMC6776796 DOI: 10.3389/fphys.2019.01244] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Accepted: 09/10/2019] [Indexed: 12/15/2022] Open
Abstract
Biological methane formation is associated with anoxic environments and the activity of anaerobic prokaryotes (Archaea). However, recent studies have confirmed methane release from eukaryotes, including plants, fungi, and animals, even in the absence of microbes and in the presence of oxygen. Furthermore, it was found that aerobic methane emission in plants is stimulated by a variety of environmental stress factors, leading to reactive oxygen species (ROS) generation. Further research presented evidence that molecules with sulfur and nitrogen bonded methyl groups such as methionine or choline are carbon precursors of aerobic methane formation. Once generated, methane is widely considered to be physiologically inert in eukaryotes, but several studies have found association between mammalian methanogenesis and gastrointestinal (GI) motility changes. In addition, a number of recent reports demonstrated anti-inflammatory potential for exogenous methane-based approaches in model anoxia-reoxygenation experiments. It has also been convincingly demonstrated that methane can influence the downstream effectors of transiently increased ROS levels, including mitochondria-related pro-apoptotic pathways during ischemia-reperfusion (IR) conditions. Besides, exogenous methane can modify the outcome of gasotransmitter-mediated events in plants, and it appears that similar mechanism might be active in mammals as well. This review summarizes the relevant literature on methane-producing processes in eukaryotes, and the available results that underscore its bioactivity. The current evidences suggest that methane liberation and biological effectiveness are both linked to cellular redox regulation. The data collectively imply that exogenous methane influences the regulatory mechanisms and signaling pathways involved in oxidative and nitrosative stress responses, which suggests a modulator role for methane in hypoxia-linked pathologies.
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Affiliation(s)
- Mihály Boros
- Institute of Surgical Research, Interdisciplinary Centre of Excellence, University of Szeged, Szeged, Hungary
| | - Frank Keppler
- Institute of Earth Sciences, Heidelberg University, Heidelberg, Germany
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Harvie RM, Tuck CJ, Schultz M. Evaluation of lactulose, lactose, and fructose breath testing in clinical practice: A focus on methane. JGH OPEN 2019; 4:198-205. [PMID: 32280765 PMCID: PMC7144793 DOI: 10.1002/jgh3.12240] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Accepted: 07/13/2019] [Indexed: 12/17/2022]
Abstract
Background and Aim Breath testing (BT) is used to identify carbohydrate malabsorption and small intestine bacterial overgrowth. Measuring methane alongside hydrogen is advocated to reduce false-negative studies, but the variability of methane production is unknown. The aim of this study is to examine the effect of high methane production on hydrogen excretion after ingesting lactulose, fructose, or lactose. Methods A retrospective audit was performed of patients with gastrointestinal symptoms who underwent BT. Following a low fermentable carbohydrate diet for 24-h, a fasting BT before consuming 35 ml lactulose, 35 g fructose, or lactose in 200 ml water, followed by BT every 10-15 min for up to 3-h, was performed. A positive test was defined as a ≥20 ppm rise of hydrogen or methane from baseline. A high methane producer had an initial reading of ≥5 ppm. Breath hydrogen and methane production were measured as area under the curve. Chi-squared tests were used to compare proportions of those meeting the cut-off criteria. Results Of patients, 26% (28/106) were high methane producers at their initial lactulose test. The test-retest repeatability of methane production was high, with the same methane production status before ingesting lactose in all (70/70) and before ingesting fructose in most (71/73). Methane production was highly variable during testing, with 38% (10/26) having ≥1 reading lower than baseline. Hydrogen produced by high or low methane producers did not differ (1528 [960-3645] ppm min vs 2375 [1810-3195] ppm min [P = 0.11]). Symptoms and breath test results were not positively related. Conclusion The validity of including an increase of ≥20 ppm methane to identify carbohydrate malabsorption or small intestine bacterial overgrowth should be questioned due to the variability of readings during testing.
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Affiliation(s)
- Ruth M Harvie
- Department of Medicine, Dunedin School of Medicine University of Otago Dunedin New Zealand
| | - Caroline J Tuck
- Gastrointestinal Disease Research Unit, Kingston General Hospital Queen's University Kingston Ontario Canada
| | - Michael Schultz
- Department of Medicine, Dunedin School of Medicine University of Otago Dunedin New Zealand.,Gastroenterology Otago Ltd., Marinoto Clinic Mercy Hospital Dunedin New Zealand
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Vlasova AV, Isakov VA, Pilipenko VI, Sheveleva SA, Markova YM, Polyanina AS, Maev IV. [Methanobrevibacter smithii in irritable bowel syndrome: a clinical and molecular study]. TERAPEVT ARKH 2019; 91:47-51. [PMID: 32598754 DOI: 10.26442/00403660.2019.08.000383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Indexed: 11/22/2022]
Abstract
AIM To assess the role of Methanobrevibacter smithii in patients with irritable bowel syndrome associated with small intestinal bowel overgrowth. MATERIALS AND METHODS Sixty - seven patients with IBS according to Rome IV were enrolled into the study in whom hydrogen breath test was performed. Thirty - two healthy subjects with negative breath test was used as a control. All IBS symptoms assessed daily with 5 grade Lykert scale for 7 days, stool was assessed by Brystol stool scale. M. smithii was confirmed in stool samples by PCR. RESULTS AND DISCUSSION In 67 IBS patients CH4 overproduction was found in 32 (47.7%), H2 overproduction in 31 (46.2%) and normal values in 4 (5.9%) by hydrogen breath test. M. smithii was confirmed by stool PCR in all patients with CH4 overproduction. Severity and prevalence of main clinical features of IBS were similar in both SIBO groups but were significantly higher than in control (p.
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Affiliation(s)
- A V Vlasova
- Federal Research Centre of Nutrition, Biotechnology and Food Safety
| | - V A Isakov
- Federal Research Centre of Nutrition, Biotechnology and Food Safety
| | - V I Pilipenko
- Federal Research Centre of Nutrition, Biotechnology and Food Safety
| | - S A Sheveleva
- Federal Research Centre of Nutrition, Biotechnology and Food Safety
| | - Y M Markova
- Federal Research Centre of Nutrition, Biotechnology and Food Safety
| | - A S Polyanina
- Federal Research Centre of Nutrition, Biotechnology and Food Safety
| | - I V Maev
- Yevdokimov Moscow State University of Medicine and Dentistry
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McCombe PA, Henderson RD, Lee A, Lee JD, Woodruff TM, Restuadi R, McRae A, Wray NR, Ngo S, Steyn FJ. Gut microbiota in ALS: possible role in pathogenesis? Expert Rev Neurother 2019; 19:785-805. [PMID: 31122082 DOI: 10.1080/14737175.2019.1623026] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Introduction: The gut microbiota has important roles in maintaining human health. The microbiota and its metabolic byproducts could play a role in the pathogenesis of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Areas covered: The authors evaluate the methods of assessing the gut microbiota, and also review how the gut microbiota affects the various physiological functions of the gut. The authors then consider how gut dysbiosis could theoretically affect the pathogenesis of ALS. They present the current evidence regarding the composition of the gut microbiota in ALS and in rodent models of ALS. Finally, the authors review therapies that could improve gut dysbiosis in the context of ALS. Expert opinion: Currently reported studies suggest some instances of gut dysbiosis in ALS patients and mouse models; however, these studies are limited, and more information with well-controlled larger datasets is required to make a definitive judgment about the role of the gut microbiota in ALS pathogenesis. Overall this is an emerging field that is worthy of further investigation. The authors advocate for larger studies using modern metagenomic techniques to address the current knowledge gaps.
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Affiliation(s)
- Pamela A McCombe
- Centre for Clinical Research, The University of Queensland , Brisbane , Australia.,Wesley Medical Research, Level 8 East Wing, The Wesley Hospital , Brisbane , Australia.,Department of Neurology, Royal Brisbane & Women's Hospital , Brisbane , Australia.,School of Medicine, The University of Queensland , Brisbane , Australia
| | - Robert D Henderson
- Wesley Medical Research, Level 8 East Wing, The Wesley Hospital , Brisbane , Australia.,Department of Neurology, Royal Brisbane & Women's Hospital , Brisbane , Australia.,School of Medicine, The University of Queensland , Brisbane , Australia.,Queensland Brain Institute, The University of Queensland , Brisbane , Australia
| | - Aven Lee
- Centre for Clinical Research, The University of Queensland , Brisbane , Australia
| | - John D Lee
- School of Biomedical Sciences, The University of Queensland , Brisbane , Australia
| | - Trent M Woodruff
- School of Biomedical Sciences, The University of Queensland , Brisbane , Australia
| | - Restuadi Restuadi
- Institute for Molecular Bioscience, The University of Queensland , Brisbane , Australia
| | - Allan McRae
- Institute for Molecular Bioscience, The University of Queensland , Brisbane , Australia
| | - Naomi R Wray
- Queensland Brain Institute, The University of Queensland , Brisbane , Australia.,Institute for Molecular Bioscience, The University of Queensland , Brisbane , Australia
| | - Shyuan Ngo
- Centre for Clinical Research, The University of Queensland , Brisbane , Australia.,Wesley Medical Research, Level 8 East Wing, The Wesley Hospital , Brisbane , Australia.,Department of Neurology, Royal Brisbane & Women's Hospital , Brisbane , Australia.,Queensland Brain Institute, The University of Queensland , Brisbane , Australia.,Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , Brisbane , Australia
| | - Frederik J Steyn
- Centre for Clinical Research, The University of Queensland , Brisbane , Australia.,Wesley Medical Research, Level 8 East Wing, The Wesley Hospital , Brisbane , Australia.,Department of Neurology, Royal Brisbane & Women's Hospital , Brisbane , Australia.,Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , Brisbane , Australia
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Szűcs S, Bari G, Ugocsai M, Lashkarivand RA, Lajkó N, Mohácsi Á, Szabó A, Kaszaki J, Boros M, Érces D, Varga G. Detection of Intestinal Tissue Perfusion by Real-Time Breath Methane Analysis in Rat and Pig Models of Mesenteric Circulatory Distress. Crit Care Med 2019; 47:e403-e411. [PMID: 30985462 DOI: 10.1097/ccm.0000000000003659] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVES Methane (CH4) breath test is an established diagnostic method for gastrointestinal functional disorders. Our aim was to explore the possible link between splanchnic circulatory changes and exhaled CH4 in an attempt to recognize intestinal perfusion failure. DESIGN Randomized, controlled in vivo animal study. SETTING University research laboratory. SUBJECTS Anesthetized, ventilated Sprague-Dawley rats (280 ± 30 g) and Vietnamese minipigs (31 ± 7 kg). INTERVENTIONS In the first series, CH4 was administered intraluminally into the ileum before 45 minutes mesenteric ischemia or before reperfusion in non-CH4 producer rats to test the appearance of the gas in the exhaled air. In the porcine experiments, the superior mesenteric artery was gradually obstructed during consecutive, 30-minute flow reductions and 30-minute reperfusions achieving complete occlusion after four cycles (n = 6), or nonocclusive mesenteric ischemia was induced by pericardial tamponade (n = 12), which decreased superior mesenteric artery flow from 351 ± 55 to 182 ± 67 mL/min and mean arterial pressure from 96.7 ± 18.2 to 41.5 ± 4.6 mm Hg for 60 minutes. MEASUREMENTS AND MAIN RESULTS Macrohemodynamics were monitored continuously; RBC velocity of the ileal serosa or mucosa was recorded by intravital videomicroscopy. The concentration of exhaled CH4 was measured online simultaneously with high-sensitivity photoacoustic spectroscopy. The intestinal flow changes during the occlusion-reperfusion phases were accompanied by parallel changes in breath CH4 output. Also in cardiac tamponade-induced nonocclusive intestinal ischemia, the superior mesenteric artery flow and RBC velocity correlated significantly with parallel changes in CH4 concentration in the exhaled air (Pearson's r = 0.669 or r = 0.632, respectively). CONCLUSIONS we report a combination of in vivo experimental data on a close association of an exhaled endogenous gas with acute mesenteric macro- and microvascular flow changes. Breath CH4 analysis may offer a noninvasive approach to follow the status of the splanchnic circulation.
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Affiliation(s)
- Szilárd Szűcs
- Institute of Surgical Research, Faculty of Medicine, University of Szeged, Szeged, Hungary
| | - Gábor Bari
- Institute of Surgical Research, Faculty of Medicine, University of Szeged, Szeged, Hungary
- Department of Cardiac Surgery, Faculty of Medicine, University of Szeged, Szeged, Hungary
| | - Melinda Ugocsai
- Institute of Surgical Research, Faculty of Medicine, University of Szeged, Szeged, Hungary
| | - Reza Ali Lashkarivand
- Institute of Surgical Research, Faculty of Medicine, University of Szeged, Szeged, Hungary
| | - Norbert Lajkó
- Institute of Surgical Research, Faculty of Medicine, University of Szeged, Szeged, Hungary
| | - Árpád Mohácsi
- MTA-SZTE Research Group on Photoacoustic Spectroscopy, Szeged, Hungary
| | - Anna Szabó
- Department of Optics and Quantum Electronics, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary
| | - József Kaszaki
- Institute of Surgical Research, Faculty of Medicine, University of Szeged, Szeged, Hungary
| | - Mihály Boros
- Institute of Surgical Research, Faculty of Medicine, University of Szeged, Szeged, Hungary
| | - Dániel Érces
- Institute of Surgical Research, Faculty of Medicine, University of Szeged, Szeged, Hungary
| | - Gabriella Varga
- Institute of Surgical Research, Faculty of Medicine, University of Szeged, Szeged, Hungary
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45
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Shah A, Morrison M, Burger D, Martin N, Rich J, Jones M, Koloski N, Walker MM, Talley NJ, Holtmann GJ. Systematic review with meta-analysis: the prevalence of small intestinal bacterial overgrowth in inflammatory bowel disease. Aliment Pharmacol Ther 2019; 49:624-635. [PMID: 30735254 DOI: 10.1111/apt.15133] [Citation(s) in RCA: 69] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2018] [Revised: 08/05/2018] [Accepted: 12/16/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Current data on small intestinal bacterial overgrowth (SIBO) in patients with inflammatory bowel diseases (IBD) are controversial. AIM To conduct a systematic review and meta-analysis to determine the prevalence of SIBO in patients with ulcerative colitis (UC) and Crohn's disease (CD). METHODS Electronic databases were searched up to May 2018 for studies reporting prevalence of SIBO in IBD patients. The prevalence rate of SIBO among IBD patients and the odds ratio (OR) and 95% CI of SIBO in IBD patients compared with controls were calculated. RESULTS The final dataset included 11 studies (1175 adult patients with IBD and 407 controls), all utilising breath test for diagnosis of SIBO. The proportion of SIBO in IBD patients was 22.3% (95% CI 19.92-24.68). The OR for SIBO in IBD patients was 9.51 (95% CI 3.39-26.68) compared to non-IBD controls, and high in both CD (OR = 10.86; 95% CI 2.76-42.69) and UC (OR = 7.96; 95% CI 1.66-38.35). In patients with CD, subgroup analysis showed the presence of fibrostenosing disease (OR = 7.47; 95% CI 2.51-22.20) and prior bowel surgery (OR = 2.38; 95% CI 1.65-3.44), especially resection of the ileocecal valve, increased the odds of SIBO. Individual studies suggest that combined small and large bowel disease but not disease activity may be associated with SIBO. CONCLUSIONS Overall, there is a substantial increase in the prevalence of SIBO in IBD patients compared to controls. Prior surgery and the presence of fibrostenosing disease are risk factors for SIBO in IBD.
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Affiliation(s)
- Ayesha Shah
- The University of Queensland, Faculty of Medicine and Faculty of Health and Behavioural Sciences, Brisbane, QLD, Australia
- Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Brisbane, QLD, Australia
- Translational Research Institute, Princess Alexandra Hospital, Brisbane, QLD, Australia
| | - Mark Morrison
- University of Queensland, Diamantina Institute, Microbial Biology and Metagenomics, QLD, Australia
| | - Daniel Burger
- The University of Queensland, Faculty of Medicine and Faculty of Health and Behavioural Sciences, Brisbane, QLD, Australia
- Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Brisbane, QLD, Australia
| | - Neal Martin
- The University of Queensland, Faculty of Medicine and Faculty of Health and Behavioural Sciences, Brisbane, QLD, Australia
- Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Brisbane, QLD, Australia
| | - Justin Rich
- The University of Queensland, Faculty of Medicine and Faculty of Health and Behavioural Sciences, Brisbane, QLD, Australia
- Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Brisbane, QLD, Australia
| | - Mike Jones
- Macquarie University, Department of Psychology, Sydney, NSW, Australia
| | - Natasha Koloski
- Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Brisbane, QLD, Australia
- University of Queensland, Diamantina Institute, Microbial Biology and Metagenomics, QLD, Australia
| | | | | | - Gerald J Holtmann
- The University of Queensland, Faculty of Medicine and Faculty of Health and Behavioural Sciences, Brisbane, QLD, Australia
- Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Brisbane, QLD, Australia
- Translational Research Institute, Princess Alexandra Hospital, Brisbane, QLD, Australia
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Tuteja AK, Talley NJ, Stoddard GJ, Verne GN. Double-Blind Placebo-Controlled Study of Rifaximin and Lactulose Hydrogen Breath Test in Gulf War Veterans with Irritable Bowel Syndrome. Dig Dis Sci 2019; 64:838-845. [PMID: 30370492 DOI: 10.1007/s10620-018-5344-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2018] [Accepted: 10/17/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) occurs in up to 33% of Gulf War (GW) Veterans. Alterations in gut microflora including small intestinal bacterial overgrowth (SIBO) during deployment may play a role in development of IBS. Rifaximin is a minimally absorbed antibiotic speculated to improve IBS symptoms, in part, by restoring normal gut microflora. The aim of this study was to compare rifaximin to placebo on IBS symptoms and quality of life (QOL) in GW Veterans with IBS without constipation. METHODS A double-blind, placebo-controlled study was performed. One hundred and twenty-two GW Veterans with IBS (Rome III) from our database and referral to gastroenterology and internal medicine clinics were screened. After a 2-week run-in period, 50 patients were randomized (1:1) to receive either rifaximin 550 gm or placebo twice daily for 2 weeks in a double-blind study. Patients were advised not to change their diet or medications during the study. The symptoms assessed were: (1) stool frequency, (2) stool consistency (Bristol stool scale, 1-7, very hard to watery), (3) urgency (1 = yes/0 = no daily for 7 days), (4) severity of abdominal pain (0-4, none to severe), (5) severity of bloating (1-4, none to severe), and (6) global improvement scale (1-7, substantially worse to substantially improved). These were recorded for 7 consecutive days and then averaged across the 7 days, to generate a continuous variable. The symptom data were compared after 2 weeks of treatment. QOL was assessed using IBS-QOL. The lactulose hydrogen breath test (LHBT) was performed at baseline and after 2 weeks of treatment. RESULTS Fifty Veterans were randomized to receive treatment; 3 withdrew and 3 were lost to follow-up. Data were analyzed from 44 patients (38 men, 6 women, median age 52, range 33-77 years). Rifaximin was not associated with significant improvement in global symptoms, abdominal pain, bloating, stool urgency, frequency, or consistency (all P ≥ 0.25) or QOL (all P ≥ 0.26). Normalization of SIBO by LHBT was not different between rifaximin- and placebo-treated Veterans (7 vs. 22%, P = 0. 54). CONCLUSION Rifaximin was not effective in improving IBS symptoms and QOL in GW Veterans with non-constipated IBS.
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Affiliation(s)
- Ashok K Tuteja
- George E. Whalen Veterans Affairs Medical Center, Salt Lake City, UT, USA. .,Division of Gastroenterology, Department of Medicine, School of Medicine, University of Utah, 30 N 1900 E, 4R118 SOM, Salt Lake City, UT, 84132, USA.
| | | | | | - G Nicholas Verne
- Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA.,North Florida/South Georgia Veterans Affairs Medical Center, Gainesville, FL, USA
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47
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Polag D, Keppler F. Long-term monitoring of breath methane. THE SCIENCE OF THE TOTAL ENVIRONMENT 2018; 624:69-77. [PMID: 29247906 DOI: 10.1016/j.scitotenv.2017.12.097] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Revised: 12/08/2017] [Accepted: 12/08/2017] [Indexed: 06/07/2023]
Abstract
In recent years, methane as a component of exhaled human breath has been considered as a potential bioindicator providing information on microbial activity in the intestinal tract. Several studies indicated a relationship between breath methane status and specific gastrointestinal disease. So far, almost no attention has been given to the temporal variability of breath methane production by individual persons. Thus here, for the first time, long-term monitoring was carried out measuring breath methane of three volunteers over periods between 196 and 1002days. Results were evaluated taking into consideration the health status and specific medical intervention events for each individual during the monitoring period, and included a gastroscopy procedure, a vaccination, a dietary change, and chelate therapy. As a major outcome, breath methane mixing ratios show considerable variability within a person-specific range of values. Interestingly, decreased breath methane production often coincided with gastrointestinal complaints whereas influenza infections were mostly accompanied by increased breath methane production. A gastroscopic examination as well as a change to a low-fructose diet led to a dramatic shift of methane mixing ratios from high to low methane production. In contrast, a typhus vaccination as well as single chelate injections resulted in significant short-term methane peaks. Thus, this study clearly shows that humans can change from high to low methane emitters and vice versa within relatively short time periods. In the case of low to medium methane emitters the increase observed in methane mixing ratios, likely resulting from immune reactions and inflammatory processes, might indicate non-microbial methane formation under aerobic conditions. Although detailed reaction pathways are not yet known, aerobic methane formation might be related to cellular oxidative-reductive stress reactions. However, a detailed understanding of the pathways involved in human methane formation is necessary to enable comprehensive interpretation of methane breath levels.
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Affiliation(s)
- Daniela Polag
- Institute of Earth Sciences, Heidelberg University, Im Neuenheimer Feld 236, D-69120 Heidelberg, Germany.
| | - Frank Keppler
- Institute of Earth Sciences, Heidelberg University, Im Neuenheimer Feld 236, D-69120 Heidelberg, Germany
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48
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Methanogens in humans: potentially beneficial or harmful for health. Appl Microbiol Biotechnol 2018; 102:3095-3104. [DOI: 10.1007/s00253-018-8871-2] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2017] [Revised: 02/13/2018] [Accepted: 02/14/2018] [Indexed: 12/18/2022]
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Wolf PG, Parthasarathy G, Chen J, O’Connor HM, Chia N, Bharucha AE, Gaskins HR. Assessing the colonic microbiome, hydrogenogenic and hydrogenotrophic genes, transit and breath methane in constipation. Neurogastroenterol Motil 2017; 29:1-9. [PMID: 28295896 PMCID: PMC5593760 DOI: 10.1111/nmo.13056] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2016] [Accepted: 02/06/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND Differences in the gut microbiota and breath methane production have been observed in chronic constipation, but the relationship between colonic microbiota, transit, and breath tests remains unclear. METHODS In 25 healthy and 25 constipated females we evaluated the sigmoid colonic mucosal and fecal microbiota using 16S rRNA gene sequencing, abundance of hydrogenogenic FeFe (FeFe-hydA) and hydrogenotrophic (methyl coenzyme M reductase A [mrcA] and dissimilatory sulfite reductase A [dsrA]) genes with real-time qPCR assays, breath hydrogen and methane levels after oral lactulose, and colonic transit with scintigraphy. KEY RESULTS Breath hydrogen and methane were not correlated with constipation, slow colon transit, or with abundance of corresponding genes. After adjusting for colonic transit, the abundance of FeFehydA, dsrA, and mcrA were greater (P<.005) in colonic mucosa, but not stool, of constipated patients. The abundance of the selected functional gene targets also correlated with that of selected taxa. The colonic mucosal abundance of FeFe-hydA, but not mcrA, correlated positively (P<.05) with breath methane production, slow colonic transit, and overall microbiome composition. In the colonic mucosa and feces, the abundance of hydrogenogenic and hydrogenotrophic genes were positively correlated (P<.05). Breath methane production was not associated with constipation or colonic transit. CONCLUSIONS & INFERENCES Corroborating our earlier findings with 16S rRNA genes, colonic mucosal but not fecal hydrogenogenic and hydrogenotrophic genes were more abundant in constipated vs. healthy subjects independent of colonic transit. Breath gases do not directly reflect the abundance of target genes contributing to their production.
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Affiliation(s)
- Patricia G. Wolf
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA
| | - Gopanandan Parthasarathy
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Jun Chen
- Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
| | - Helen M. O’Connor
- Clinical Research and Trials Unit, Center for Clinical and Translational Science, Mayo Clinic, Rochester, MN, 55905 USA
| | - Nicholas Chia
- Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA,Microbiome Program, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA
| | - Adil E. Bharucha
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - H. Rex Gaskins
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA,Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA
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50
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Park YM, Lee YJ, Hussain Z, Lee YH, Park H. The effects and mechanism of action of methane on ileal motor function. Neurogastroenterol Motil 2017; 29. [PMID: 28417537 DOI: 10.1111/nmo.13077] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Accepted: 03/02/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Methane has been associated with constipation-predominant irritable bowel syndrome, slowing intestinal transit time by augmenting contractile activity. However, the precise mechanism underlying this effect remains unclear. Therefore, we investigated the mechanisms underlying the effect of methane on contractile activity, and whether such effects are mediated by nerve impulses or muscular contraction. METHODS We connected guinea pig ileal muscle strips to a force/tension transducer and measured amplitudes of contraction in response to electrical field stimulation (EFS; 1, 2, 8, 16 Hz) following methane infusion in the presence of tetradotoxin (TTX), atropine, guanethidine, or GR 113808. We then performed calcium imaging using Oregon Green 488 BAPTA-1 AM in order to visualize changes in calcium fluorescence in response to EFS following methane infusion in the presence of TTX, atropine, or a high K+ solution. KEY RESULTS Methane significantly increased amplitudes of contraction (P<.05), while treatment with TTX abolished such contraction. Methane-induced increases in amplitude were inhibited when lower-frequency (1, 2 Hz) EFS was applied following atropine infusion (P<.05). Neither guanethidine nor GR 113808 significantly altered contraction amplitudes. Methane significantly increased calcium fluorescence, while this increase was attenuated following atropine infusion (P<.05). Although calcium fluorescence was increased by the high K+ solution under pretreatment with TTX, the intensity of fluorescence remained unchanged after methane infusion. CONCLUSIONS AND INFERENCES The actions of methane on the intestine are influenced by the cholinergic pathway of the enteric nervous system. Our findings support the classification of methane as a gasotransmitter.
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Affiliation(s)
- Y M Park
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Y J Lee
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Z Hussain
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Y H Lee
- Department of Physiology, Yonsei University College of Medicine, Seoul, Korea
| | - H Park
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
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