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1
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Lima MFDO, Nogueira VB, Maury W, Wilson ME, Júnior METD, Teixeira DG, Bezerra Jeronimo SM. Altered Cellular Pathways in the Blood of Patients With Guillain-Barre Syndrome. J Peripher Nerv Syst 2025; 30:e70012. [PMID: 40099626 DOI: 10.1111/jns.70012] [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: 07/24/2024] [Revised: 02/03/2025] [Accepted: 03/03/2025] [Indexed: 03/20/2025]
Abstract
BACKGROUND AND AIMS Guillain-Barré syndrome (GBS) is a rare disorder, with a global incidence ranging from 1 to 2 individuals per 100,000 people/year. Infections and vaccines have been implicated as causes triggering GBS. The aim of the study was to identify host genes involved in the pathogenesis of GBS when Zika (ZIKV) and Chikungunya viruses (CHIKV) were introduced in Brazil. METHODS A case-control study of GBS was performed when ZIKV and CHIKV were introduced into a naïve population. GBS was studied during both acute and postacute phases. RNA sequencing was conducted using whole blood. RESULTS GBS typically manifested a week after rash and fever; acute inflammatory demyelinating polyradiculoneuropathy was more frequent. None of the GBS cases had a poor outcome. Serological assays for ZIKV and CHIKV revealed high titers of immunoglobulin G for both viruses in 9 out of 11 subjects. Metatranscriptomic analyses unveiled an increased abundance of reads attributed to Pseudomonas tolaasii and Toxoplasma gondii in the acute phase. Analysis of differentially expressed host genes during the acute phase revealed altered expression of genes associated with axogenesis, synapse assembly, and presynapse organization. Moreover, genes upregulated during acute GBS were primarily related to inflammation and the inflammasome pathways, including AIM2, NLR family genes and LRR-protein genes, and IL-10. INTERPRETATION These findings suggest that inflammasome activation via AIM2 could play a role in tissue damage during GBS. Further investigation into the general activation of innate inflammatory responses is warranted to elucidate their potential contribution to the pathology of GBS.
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Affiliation(s)
| | - Viviane Brito Nogueira
- Graduate Program in Health Sciences, Health Sciences Center, Federal University of Rio Grande do Norte, Natal, Brazil
| | - Wendy Maury
- Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA
| | - Mary Edythe Wilson
- Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA
- Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA
- Veterans' Affairs Medical Center, Iowa City, Iowa, USA
| | - Mário Emílio Teixeira Dourado Júnior
- Institute of Tropical Medicine of Rio Grande do Norte, Federal University of Rio Grande do Norte, Natal, Brazil
- Onofre Lopes University Hospital and Department of Integrative Medicine, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil
| | - Diego Gomes Teixeira
- Institute of Tropical Medicine of Rio Grande do Norte, Federal University of Rio Grande do Norte, Natal, Brazil
| | - Selma Maria Bezerra Jeronimo
- Graduate Program in Health Sciences, Health Sciences Center, Federal University of Rio Grande do Norte, Natal, Brazil
- Institute of Tropical Medicine of Rio Grande do Norte, Federal University of Rio Grande do Norte, Natal, Brazil
- Department of Biochemistry, Biosciences Center, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil
- Institute of Science and Technology of Tropical Diseases, Natal, Rio Grande do Norte, Brazil
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2
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Zhang X, Zhang X, Yang Y. Update of gut gas metabolism in ulcerative colitis. Expert Rev Gastroenterol Hepatol 2024; 18:339-349. [PMID: 39031456 DOI: 10.1080/17474124.2024.2383635] [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: 12/11/2023] [Accepted: 07/19/2024] [Indexed: 07/22/2024]
Abstract
INTRODUCTION Ulcerative colitis (UC) is a chronic, nonspecific inflammatory disease of the intestine. The intestinal microbiota is essential in the occurrence and development of UC. Gut gases are produced via bacterial fermentation or chemical interactions, which can reveal altered intestinal microbiota, abnormal cellular metabolism, and inflammation responses. Recent studies have demonstrated that UC patients have an altered gut gas metabolism. AREAS COVERED In this review, we integrate gut gas metabolism advances in UC and discuss intestinal gases' clinical values as new biomarkers or therapeutic targets for UC, providing the foundation for further research. Literature regarding gut gas metabolism and its significance in UC from inception to October 2023 was searched on the MEDLINE database and references from relevant articles were investigated. EXPERT OPINION Depending on their type, concentration, and volume, gut gases can induce or alleviate clinical symptoms and regulate intestinal motility, inflammatory responses, immune function, and oxidative stress, significantly impacting UC. Gut gases may function as new biomarkers and provide potential diagnostic or therapeutic targets for UC.
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Affiliation(s)
- Xiaohan Zhang
- Medical School, Nankai University, Tianjin, China
- Microbiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Xiuli Zhang
- Microbiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Yunsheng Yang
- Microbiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
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3
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Cena JAD, Belmok A, Kyaw CM, Dame-Teixeira N. The Archaea domain: Exploring historical and contemporary perspectives with in silico primer coverage analysis for future research in Dentistry. Arch Oral Biol 2024; 161:105936. [PMID: 38422909 DOI: 10.1016/j.archoralbio.2024.105936] [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: 01/13/2024] [Revised: 02/07/2024] [Accepted: 02/21/2024] [Indexed: 03/02/2024]
Abstract
OBJECTIVE The complete picture of how the human microbiome interacts with its host is still largely unknown, particularly concerning microorganisms beyond bacteria. Although existing in very low abundance and not directly linked to causing diseases, archaea have been detected in various sites of the human body, including the gastrointestinal tract, oral cavity, skin, eyes, respiratory and urinary systems. But what exactly are these microorganisms? In the early 1990 s, archaea were classified as a distinct domain of life, sharing a more recent common ancestor with eukaryotes than with bacteria. While archaea's presence and potential significance in Dentistry remain under-recognized, there are concerns that they may contribute to oral dysbiosis. However, detecting archaea in oral samples presents challenges, including difficulties in culturing, the selection of DNA extraction methods, primer design, bioinformatic analysis, and databases. DESIGN This is a comprehensive review on the oral archaeome, presenting an in-depth in silico analysis of various primers commonly used for detecting archaea in human body sites. RESULTS Among several primer pairs used for detecting archaea in human samples across the literature, only one specifically designed for detecting methanogenic archaea in stool samples, exhibited exceptional coverage levels for the domain and various archaea phyla. CONCLUSIONS Our in silico analysis underscores the need for designing new primers targeting not only methanogenic archaea but also nanoarchaeal and thaumarchaeota groups to gain a comprehensive understanding of the archaeal oral community. By doing so, researchers can pave the way for further advancements in the field of oral archaeome research.
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Affiliation(s)
| | - Aline Belmok
- Institute of Biology, University of Brasilia, Brazil
| | | | - Naile Dame-Teixeira
- Department of Dentistry, School of Health Sciences, University of Brasilia, Brazil; Division of Oral Biology, School of Dentistry, University of Leeds, UK.
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4
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Cisek AA, Szymańska E, Aleksandrzak-Piekarczyk T, Cukrowska B. The Role of Methanogenic Archaea in Inflammatory Bowel Disease-A Review. J Pers Med 2024; 14:196. [PMID: 38392629 PMCID: PMC10890621 DOI: 10.3390/jpm14020196] [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: 12/31/2023] [Revised: 01/28/2024] [Accepted: 02/08/2024] [Indexed: 02/24/2024] Open
Abstract
Methanogenic archaea are a part of the commensal gut microbiota responsible for hydrogen sink and the efficient production of short-chain fatty acids. Dysbiosis of methanogens is suspected to play a role in pathogenesis of variety of diseases, including inflammatory bowel disease (IBD). Unlike bacteria, the diversity of archaea seems to be higher in IBD patients compared to healthy subjects, whereas the prevalence and abundance of gut methanogens declines in IBD, especially in ulcerative colitis. To date, studies focusing on methanogens in pediatric IBD are very limited; nevertheless, the preliminary results provide some evidence that methanogens may be influenced by the chronic inflammatory process in IBD. In this review, we demonstrated the development and diversity of the methanogenic community in IBD, both in adults and children.
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Affiliation(s)
- Agata Anna Cisek
- Department of Pathomorphology, The Children's Memorial Health Institute, Av. Dzieci Polskich 20, 04-730 Warsaw, Poland
| | - Edyta Szymańska
- Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children's Memorial Health Institute, Av. Dzieci Polskich 20, 04-730 Warsaw, Poland
| | | | - Bożena Cukrowska
- Department of Pathomorphology, The Children's Memorial Health Institute, Av. Dzieci Polskich 20, 04-730 Warsaw, Poland
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5
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Lin Y, Manalili D, Khodabakhsh A, Cristescu SM. Real-Time Measurement of CH 4 in Human Breath Using a Compact CH 4/CO 2 Sensor. SENSORS (BASEL, SWITZERLAND) 2024; 24:1077. [PMID: 38400235 PMCID: PMC10893524 DOI: 10.3390/s24041077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 02/05/2024] [Accepted: 02/05/2024] [Indexed: 02/25/2024]
Abstract
The presence of an elevated amount of methane (CH4) in exhaled breath can be used as a non-invasive tool to monitor certain health conditions. A compact, inexpensive and transportable CH4 sensor is thus very interesting for this purpose. In addition, if the sensor is also able to simultaneously measure carbon dioxide (CO2), one can extract the end-tidal concentration of exhaled CH4. Here, we report on such a sensor based on a commercial detection module using tunable diode laser absorption spectroscopy. It was found that the measured CH4/CO2 values exhibit a strong interference with water vapor. Therefore, correction functions were experimentally identified and validated for both CO2 and CH4. A custom-built breath sampler was developed and tested with the sensor for real-time measurements of CH4 and CO2 in exhaled breath. As a result, the breath sensor demonstrated the capability of accurately measuring the exhaled CH4 and CO2 profiles in real-time. We obtained minimum detection limits of ~80 ppbv for CH4 and ~700 ppmv for CO2 in 1.5 s measurement time.
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Affiliation(s)
| | | | | | - Simona M. Cristescu
- Life Science Trace Detection Laboratory, Department of Analytical Chemistry and Chemometrics, Institute for Molecules and Materials, Radboud University, 6525 AJ Nijmegen, The Netherlands; (Y.L.); (D.M.); (A.K.)
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6
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Dawson B, Drewer J, Roberts T, Levy P, Heal M, Cowan N. Measurements of methane and nitrous oxide in human breath and the development of UK scale emissions. PLoS One 2023; 18:e0295157. [PMID: 38091323 PMCID: PMC10718453 DOI: 10.1371/journal.pone.0295157] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Accepted: 11/15/2023] [Indexed: 12/18/2023] Open
Abstract
Exhaled human breath can contain small, elevated concentrations of methane (CH4) and nitrous oxide (N2O), both of which contribute to global warming. These emissions from humans are not well understood and are rarely quantified in global greenhouse gas inventories. This study investigated emissions of CH4 and N2O in human breath from 104 volunteers in the UK population, to better understand what drives these emissions and to quantify national-scale estimates. A total of 328 breath samples were collected, and age, sex, dietary preference, and smoking habits were recorded for every participant. The percentage of methane producers (MPs) identified in this study was 31%. The percentage of MPs was higher in older age groups with 25% of people under the age of 30 classified as MPs compared to 40% in the 30+ age group. Females (38%) were more likely to be MPs than males (25%), though overall concentrations emitted from both MP groups were similar. All participants were found to emit N2O in breath, though none of the factors investigated explained the differences in emissions. Dietary preference was not found to affect CH4 or N2O emissions from breath in this study. We estimate a total emission of 1.04 (0.86-1.40) Gg of CH4 and 0.069 (0.066-0.072) Gg of N2O in human breath annually in the UK, the equivalent of 53.9 (47.8-60.0) Gg of CO2. In terms of magnitude, these values are approximately 0.05% and 0.1% of the total emissions of CH4 and N2O reported in the UK national greenhouse gas inventories.
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Affiliation(s)
- Ben Dawson
- UK Centre for Ecology and Hydrology, Bush Estate, Midlothian, United Kingdom
- The University of Edinburgh, School of Chemistry, Edinburgh, United Kingdom
| | - Julia Drewer
- UK Centre for Ecology and Hydrology, Bush Estate, Midlothian, United Kingdom
| | - Toby Roberts
- UK Centre for Ecology and Hydrology, Bush Estate, Midlothian, United Kingdom
| | - Peter Levy
- UK Centre for Ecology and Hydrology, Bush Estate, Midlothian, United Kingdom
| | - Mathew Heal
- The University of Edinburgh, School of Chemistry, Edinburgh, United Kingdom
| | - Nicholas Cowan
- UK Centre for Ecology and Hydrology, Bush Estate, Midlothian, United Kingdom
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7
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Volmer JG, McRae H, Morrison M. The evolving role of methanogenic archaea in mammalian microbiomes. Front Microbiol 2023; 14:1268451. [PMID: 37727289 PMCID: PMC10506414 DOI: 10.3389/fmicb.2023.1268451] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Accepted: 08/18/2023] [Indexed: 09/21/2023] Open
Abstract
Methanogenic archaea (methanogens) represent a diverse group of microorganisms that inhabit various environmental and host-associated microbiomes. These organisms play an essential role in global carbon cycling given their ability to produce methane, a potent greenhouse gas, as a by-product of their energy production. Recent advances in culture-independent and -dependent studies have highlighted an increased prevalence of methanogens in the host-associated microbiome of diverse animal species. Moreover, there is increasing evidence that methanogens, and/or the methane they produce, may play a substantial role in human health and disease. This review addresses the expanding host-range and the emerging view of host-specific adaptations in methanogen biology and ecology, and the implications for host health and disease.
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Affiliation(s)
- James G. Volmer
- Centre for Microbiome Research, School of Biomedical Sciences, Queensland University of Technology (QUT), Translational Research Institute, Woolloongabba, QLD, Australia
| | - Harley McRae
- Faculty of Medicine, University of Queensland Frazer Institute, Translational Research Institute, Woolloongabba, QLD, Australia
| | - Mark Morrison
- Faculty of Medicine, University of Queensland Frazer Institute, Translational Research Institute, Woolloongabba, QLD, Australia
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8
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Garcia-Bonete MJ, Rajan A, Suriano F, Layunta E. The Underrated Gut Microbiota Helminths, Bacteriophages, Fungi, and Archaea. Life (Basel) 2023; 13:1765. [PMID: 37629622 PMCID: PMC10455619 DOI: 10.3390/life13081765] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 08/12/2023] [Accepted: 08/13/2023] [Indexed: 08/27/2023] Open
Abstract
The microbiota inhabits the gastrointestinal tract, providing essential capacities to the host. The microbiota is a crucial factor in intestinal health and regulates intestinal physiology. However, microbiota disturbances, named dysbiosis, can disrupt intestinal homeostasis, leading to the development of diseases. Classically, the microbiota has been referred to as bacteria, though other organisms form this complex group, including viruses, archaea, and eukaryotes such as fungi and protozoa. This review aims to clarify the role of helminths, bacteriophages, fungi, and archaea in intestinal homeostasis and diseases, their interaction with bacteria, and their use as therapeutic targets in intestinal maladies.
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Affiliation(s)
- Maria Jose Garcia-Bonete
- Department of Medical Biochemistry and Cell Biology, University of Gothenburg, SE-405 30 Gothenburg, Sweden
| | - Anandi Rajan
- Department of Medical Biochemistry and Cell Biology, University of Gothenburg, SE-405 30 Gothenburg, Sweden
| | - Francesco Suriano
- Department of Medical Biochemistry and Cell Biology, University of Gothenburg, SE-405 30 Gothenburg, Sweden
| | - Elena Layunta
- Department of Medical Biochemistry and Cell Biology, University of Gothenburg, SE-405 30 Gothenburg, Sweden
- Instituto de Investigación Sanitaria de Aragón (IIS Aragón), 50009 Zaragoza, Spain
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9
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Kwaśny M, Bombalska A. Optical Methods of Methane Detection. SENSORS (BASEL, SWITZERLAND) 2023; 23:2834. [PMID: 36905038 PMCID: PMC10007260 DOI: 10.3390/s23052834] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 03/02/2023] [Accepted: 03/02/2023] [Indexed: 06/18/2023]
Abstract
Methane is the most frequently analyzed gas with different concentrations ranging from single ppm or ppb to 100%. There are a wide range of applications for gas sensors including urban uses, industrial uses, rural measurements, and environment monitoring. The most important applications include the measurement of anthropogenic greenhouse gases in the atmosphere and methane leak detection. In this review, we discuss common optical methods used for detecting methane such as non-dispersive infrared (NIR) technology, direct tunable diode spectroscopy (TDLS), cavity ring-down spectroscopy (CRDS), cavity-enhanced absorption spectroscopy (CEAS), lidar techniques, and laser photoacoustic spectroscopy. We also present our own designs of laser methane analyzers for various applications (DIAL, TDLS, NIR).
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Affiliation(s)
| | - Aneta Bombalska
- Institute of Optoelectronics, Military University of Technology, gen. Sylwestra Kaliskiego 2, 00-908 Warsaw, Poland
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10
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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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11
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Djemai K, Drancourt M, Tidjani Alou M. Bacteria and Methanogens in the Human Microbiome: a Review of Syntrophic Interactions. MICROBIAL ECOLOGY 2022; 83:536-554. [PMID: 34169332 DOI: 10.1007/s00248-021-01796-7] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Accepted: 06/14/2021] [Indexed: 06/13/2023]
Abstract
Methanogens are microorganisms belonging to the Archaea domain and represent the primary source of biotic methane. Methanogens encode a series of enzymes which can convert secondary substrates into methane following three major methanogenesis pathways. Initially recognized as environmental microorganisms, methanogens have more recently been acknowledged as host-associated microorganisms after their detection and initial isolation in ruminants in the 1950s. Methanogens have also been co-detected with bacteria in various pathological situations, bringing their role as pathogens into question. Here, we review reported associations between methanogens and bacteria in physiological and pathological situations in order to understand the metabolic interactions explaining these associations. To do so, we describe the origin of the metabolites used for methanogenesis and highlight the central role of methanogens in the syntrophic process during carbon cycling. We then focus on the metabolic abilities of co-detected bacterial species described in the literature and infer from their genomes the probable mechanisms of their association with methanogens. The syntrophic interactions between bacteria and methanogens are paramount to gut homeostasis. Therefore, any dysbiosis affecting methanogens might impact human health. Thus, the monitoring of methanogens may be used as a bio-indicator of dysbiosis. Moreover, new therapeutic approaches can be developed based on their administration as probiotics. We thus insist on the importance of investigating methanogens in clinical microbiology.
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Affiliation(s)
- Kenza Djemai
- IRD, MEPHI, IHU Méditerranée Infection, Aix-Marseille-University, 19-12 Bd Jean Moulin, 13005, Marseille, France
- IHU Méditerranée Infection, Marseille, France
| | - Michel Drancourt
- IRD, MEPHI, IHU Méditerranée Infection, Aix-Marseille-University, 19-12 Bd Jean Moulin, 13005, Marseille, France
| | - Maryam Tidjani Alou
- IRD, MEPHI, IHU Méditerranée Infection, Aix-Marseille-University, 19-12 Bd Jean Moulin, 13005, Marseille, France.
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12
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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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13
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Quantitative GC-TCD Measurements of Major Flatus Components: A Preliminary Analysis of the Diet Effect. SENSORS 2022; 22:s22030838. [PMID: 35161583 PMCID: PMC8840200 DOI: 10.3390/s22030838] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 01/14/2022] [Accepted: 01/21/2022] [Indexed: 02/01/2023]
Abstract
The impact of diet and digestive disorders in flatus composition remains largely unexplored. This is partially due to the lack of standardized sampling collection methods, and the easy atmospheric contamination. This paper describes a method to quantitatively determine the major gases in flatus and their application in a nutritional intervention. We describe how to direct sample flatus into Tedlar bags, and simultaneous analysis by gas chromatography–thermal conductivity detection (GC–TCD). Results are analyzed by univariate hypothesis testing and by multilevel principal component analysis. The reported methodology allows simultaneous determination of the five major gases with root mean measurement errors of 0.8% for oxygen (O2), 0.9% for nitrogen (N2), 0.14% for carbon dioxide (CO2), 0.11% for methane (CH4), and 0.26% for hydrogen (H2). The atmospheric contamination was limited to 0.86 (95% CI: [0.7–1.0])% for oxygen and 3.4 (95% CI: [1.4–5.3])% for nitrogen. As an illustration, the method has been successfully applied to measure the response to a nutritional intervention in a reduced crossover study in healthy subjects.
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14
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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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15
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Methanogen Abundance Thresholds Capable of Differentiating In Vitro Methane Production in Human Stool Samples. Dig Dis Sci 2021; 66:3822-3830. [PMID: 33247793 DOI: 10.1007/s10620-020-06721-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 11/15/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND Intestinal methane (CH4) gas production has been associated with a number of clinical conditions and may have important metabolic and physiological effects. AIMS In this study, taxonomic and functional gene analyses and in vitro CH4 gas measurements were used to determine if molecular markers can potentially serve as clinical tests for colonic CH4 production. METHODS We performed a cross-sectional study involving full stool samples collected from 33 healthy individuals. In vitro CH4 gas measurements were obtained after 2-h incubation of stool samples and used to characterize samples as CH4 positive (CH4+) and CH4 negative (CH4-; n = 10 and 23, respectively). Next, we characterized the fecal microbiota through high-throughput DNA sequencing with a particular emphasis on archaeal phylum Euryarchaeota. Finally, qPCR analyses, targeting the mcrA gene, were done to determine the ability to differentiate CH4+ versus CH4- samples and to delineate major methanogen species associated with CH4 production. RESULTS Methanobrevibacter was found to be the most abundant methane producer and its relative abundance provides a clear distinction between CH4+ versus CH4- samples. Its sequencing-based relative abundance detection threshold for CH4 production was calculated to be 0.097%. The qPCR-based detection threshold separating CH4+ versus CH4- samples, based on mcrA gene copies, was 5.2 × 105 copies/g. CONCLUSION Given the decreased time-burden placed on patients, a qPCR-based test on a fecal sample can become a valuable tool in clinical assessment of CH4 producing status.
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Richard N, Desprez C, Wuestenberghs F, Leroi A, Gourcerol G, Melchior C. The effectiveness of rotating versus single course antibiotics for small intestinal bacterial overgrowth. United European Gastroenterol J 2021; 9:645-654. [PMID: 34241973 PMCID: PMC8280793 DOI: 10.1002/ueg2.12116] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Accepted: 04/16/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Small intestinal bacterial overgrowth treatment is usually based on antibiotics with no guidelines available. OBJECTIVE This study aimed to investigate the efficacy of different antibiotics to treat small intestinal bacterial overgrowth. METHODS Consecutive patients referred to our tertiary center and diagnosed with intestinal bacterial overgrowth were retrospectively included. Patients were diagnosed using a 75 g glucose breath test. Patients were treated either with a single antibiotic (quinolone or azole) or rotating antibiotics (quinolone and azole, one after the other) for 10 consecutive days per month for 3 months. A negative glucose breath test after antibiotic treatment was considered as remission. Quality of life (GIQLI) and gastrointestinal severity (IBS-SSS) were assessed before and after antibiotic treatment. Symptomatic evaluation was realized in simple blind of glucose breath test result: patients were unaware of their results. RESULTS Between August 2005 and February 2020, 223 patients were included in the analysis (female 79.8%, mean age 50.2 ± 15.7 years). Remission was observed in 119 patients (53.4%) after one course of antibiotics and was more frequent in patients receiving rotating antibiotics than in patients receiving a single antibiotic (70.0% vs. 50.8%, p = 0.050). Remission was associated with a significant improvement in quality of life (p = 0.035) and in bloating (p = 0.004). CONCLUSION In this study, the treatment of small intestinal bacterial overgrowth using rotating antibiotics was more effective than treatment using a single course of antibiotic. Remission was associated with improvement in both quality of life and bloating.
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Affiliation(s)
- Nicolas Richard
- Gastroenterology DepartmentRouen University HospitalRouenFrance
| | - Charlotte Desprez
- INSERM UMR 1073Institute for Research and Innovation in BiomedicineNormandy UniversityRouenFrance
- Physiology DepartmentRouen University HospitalRouenFrance
| | - Fabien Wuestenberghs
- INSERM UMR 1073Institute for Research and Innovation in BiomedicineNormandy UniversityRouenFrance
- Physiology DepartmentRouen University HospitalRouenFrance
- Department of Gastroenterology and HepatologyCHU UCL Namur, Godinne University Hospital, UCLouvainYvoirBelgium
| | - Anne‐Marie Leroi
- INSERM UMR 1073Institute for Research and Innovation in BiomedicineNormandy UniversityRouenFrance
- Physiology DepartmentRouen University HospitalRouenFrance
- INSERM CIC 1404Rouen University HospitalRouenFrance
| | - Guillaume Gourcerol
- INSERM UMR 1073Institute for Research and Innovation in BiomedicineNormandy UniversityRouenFrance
- Physiology DepartmentRouen University HospitalRouenFrance
| | - Chloé Melchior
- Gastroenterology DepartmentRouen University HospitalRouenFrance
- INSERM UMR 1073Institute for Research and Innovation in BiomedicineNormandy UniversityRouenFrance
- INSERM CIC 1404Rouen University HospitalRouenFrance
- Department of Molecular and Clinical MedicineInstitute of MedicineSahlgrenska AcademyUniversity of GothenburgGothenburgSweden
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18
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Cerling TE, Bernasconi SM, Hofstetter LS, Jaggi M, Wyss F, Rudolf von Rohr C, Clauss M. CH4/CO2 Ratios and Carbon Isotope Enrichment Between Diet and Breath in Herbivorous Mammals. Front Ecol Evol 2021. [DOI: 10.3389/fevo.2021.638568] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Breath and diet samples were collected from 29 taxa of animals at the Zurich and Basel Zoos to characterize the carbon isotope enrichment between breath and diet. Diet samples were measured for δ13C and breath samples for CH4/CO2 ratios and for the respired component of δ13C using the Keeling plot approach. Different digestive physiologies included coprophagous and non-coprophagous hindgut fermenters, and non-ruminant and ruminant foregut fermenters. Isotope enrichments from diet to breath were 0.8 ± 0.9‰, 3.5 ± 0.8‰, 2.3 ± 0.4‰, and 4.1 ± 1.0‰, respectively. CH4/CO2 ratios were strongly correlated with isotope enrichments for both hindgut and foregut digestive strategies, although CH4 production was not the sole reason for isotope enrichment. Average CH4/CO2 ratios per taxon ranged over several orders of magnitude from 10–5 to 10–1. The isotope enrichment values for diet-breath can be used to further estimate the isotope enrichment from diet-enamel because Passey et al. (2005b) found a nearly constant isotope enrichment for breath-enamel for diverse mammalian taxa. The understanding of isotope enrichment factors from diet to breath and diet to enamel will have important applications in the field of animal physiology, and possibly also for wildlife ecology and paleontology.
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Nichols BL, Baker RD, Baker SS. Overview of Breath Testing in Clinical Practice in North America. JPGN REPORTS 2021; 2:e027. [PMID: 37206939 PMCID: PMC10191541 DOI: 10.1097/pg9.0000000000000027] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 06/29/2020] [Indexed: 05/21/2023]
Abstract
Human breath is an easily, noninvasively obtained substance. It offers insight into metabolism and is used to diagnose disaccharide malabsorption, infection, small bowel bacterial over growth, and transit times. Herein, we discuss the readily available clinical breath tests, how they function, how they are administered and interpreted and some pitfalls in their use.
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Affiliation(s)
- Buford L. Nichols
- From the Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX
| | - Robert D. Baker
- Department of Pediatrics, University at Buffalo, Buffalo, NY
| | - Susan S. Baker
- Department of Pediatrics, University at Buffalo, Buffalo, NY
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20
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Wang X, Li J, Li N, Guan K, Yin D, Zhang H, Ding G, Hu Y. Evolution of Intestinal Gases and Fecal Short-Chain Fatty Acids Produced in vitro by Preterm Infant Gut Microbiota During the First 4 Weeks of Life. Front Pediatr 2021; 9:726193. [PMID: 34646797 PMCID: PMC8504453 DOI: 10.3389/fped.2021.726193] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 08/27/2021] [Indexed: 12/31/2022] Open
Abstract
Background: The production of intestinal gases and fecal short-chain fatty acids (SCFAs) by infant gut microbiota may have a significant impact on their health, but information about the composition and volume of intestinal gases and SCFA profiles in preterm infants is scarce. Objective: This study examined the change of the composition and volume of intestinal gases and SCFA profiles produced by preterm infant gut microbiota in vitro during the first 4 weeks of life. Methods: Fecal samples were obtained at five time points (within 3 days, 1 week, 2 weeks, 3 weeks, and 4 weeks) from 19 preterm infants hospitalized in the neonatal intensive care unit (NICU) of Shanghai Children's Hospital, Shanghai Jiao Tong University between May and July 2020. These samples were initially inoculated into four different media containing lactose (LAT), fructooligosaccharide (FOS), 2'-fucosyllactose (FL-2), and galactooligosaccharide (GOS) and thereafter fermented for 24 h under conditions mimicking those of the large intestine at 37.8°C under anaerobic conditions. The volume of total intestinal gases and the concentrations of individual carbon dioxide (CO2), hydrogen (H2), methane (CH4), and hydrogen sulfide (H2S) were measured by a gas analyzer. The concentrations of total SCFAs, individual acetic acid, propanoic acid, butyric acid, isobutyric acid, pentanoic acid, and valeric acid were measured by gas chromatography (GC). Results: The total volume of intestinal gases (ranging from 0.01 to 1.64 ml in medium with LAT; 0-1.42 ml with GOS; 0-0.91 ml with FOS; and 0-0.44 ml with FL-2) and the concentrations of CO2, H2, H2S, and all six fecal SCFAs increased with age (p-trends < 0.05). Among them, CO2 was usually the predominant intestinal gas, and acetic acid was usually the predominant SCFA. When stratified by birth weight (<1,500 and ≥1,500 g), gender, and delivery mode, the concentration of CO2 was more pronounced among infants whose weight was ≥1,500 g than among those whose weight was <1,500 g (p-trends < 0.05). Conclusions: Our findings suggested that the intestinal gases and SCFAs produced by preterm infant gut microbiota in vitro increased with age during the first 4 weeks of life.
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Affiliation(s)
- Xuefang Wang
- Department of Neonatology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Juan Li
- Department of Neonatology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Na Li
- Department of Neonatology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Kunyu Guan
- Department of Neonatology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Di Yin
- Department of Neonatology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Huating Zhang
- Department of Neonatology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Guodong Ding
- Department of Respiratory, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Yong Hu
- Department of Neonatology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
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21
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Gu P, Patel D, Lakhoo K, Ko J, Liu X, Chang B, Pan D, Lentz G, Sonesen M, Estiandan R, Lin E, Pimentel M, Rezaie A. Breath Test Gas Patterns in Inflammatory Bowel Disease with Concomitant Irritable Bowel Syndrome-Like Symptoms: A Controlled Large-Scale Database Linkage Analysis. Dig Dis Sci 2020; 65:2388-2396. [PMID: 31754993 DOI: 10.1007/s10620-019-05967-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2019] [Accepted: 11/16/2019] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Breath testing (BT) has gained interest for diagnosing small intestinal bacterial overgrowth (SIBO) in IBD patients with irritable bowel syndrome (IBS) overlap. We aim to characterize the rate of SIBO and BT gas patterns in IBD patients with IBS-like symptoms compared to non-IBD patients. METHODS A database of 14,847 consecutive lactulose BTs was developed from patients with IBS-like symptoms between November 2005 and October 2013. BTs were classified as normal, H2 predominant, CH4 predominant, and flatline based on criteria established from the literature. BT data linkage with electronic health records and chart review identified IBD patients along with disease phenotype, location, severity, and antibiotic response. Poisson loglinear model evaluated differences in gas patterns between the two groups. RESULTS After excluding patients with repeat breath tests, we identified 486 IBD and 10,505 non-IBD patients with at least one BT. Positive BT was present in 57% (n = 264) of IBD patients. Crohn's disease (odds ratio (OR) 0.21, [95% confidence interval (CI) 0.11-0.38]) and ulcerative colitis (OR 0.39, [95% CI 0.22-0.70]) patients were less likely to produce excess CH4. IBD patients were more likely to have flatline BT (OR 1.82, [95% CI 1.20-2.77]). In IBD patients with SIBO, 57% improved symptomatically with antibiotics. CONCLUSION In a cohort of IBD patients with IBS-like symptoms, a high rate of patients had positive BT and symptomatic improvement with antibiotics. In IBD, methanogenesis is suppressed and flatline BT is more frequent, suggesting excess hydrogenotrophic bacteria. These findings suggest methanogenic and hydrogenotrophic microorganisms as potential targets for microbiome-driven biomarkers and therapies.
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Affiliation(s)
- Phillip Gu
- Division of Digestive and Liver Diseases, University of Texas Southwestern, Dallas, TX, USA.
| | - Devin Patel
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Krutika Lakhoo
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Jeffrey Ko
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Xiaochen Liu
- Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Bianca Chang
- Section of Gastroenterology, Hepatology and Nutrition, University of Chicago, Chicago, IL, USA
| | - Dana Pan
- Division of Gastroenterology and Hepatology, University of California in Davis, Sacramento, CA, USA
| | - Greg Lentz
- Enterprise Information Services- Initiate Team, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Matthew Sonesen
- Enterprise Information Services- Initiate Team, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Renier Estiandan
- Enterprise Information Services- Initiate Team, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Eugenia Lin
- Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Mark Pimentel
- Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Ali Rezaie
- Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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22
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Guindo CO, Drancourt M, Grine G. Digestive tract methanodrome: Physiological roles of human microbiota-associated methanogens. Microb Pathog 2020; 149:104425. [PMID: 32745665 DOI: 10.1016/j.micpath.2020.104425] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 07/21/2020] [Accepted: 07/27/2020] [Indexed: 02/07/2023]
Abstract
Methanogens are the archaea most commonly found in humans, in particular in the digestive tract and are an integral part of the digestive microbiota. They are present in humans from the earliest moments of life and represent the only known source of methane production to date. They are notably detected in humans by microscopy, fluorescent in situ hybridization, molecular biology including PCR-sequencing, metagenomics, matrix-assisted laser desorption ionization time-of-flight mass spectrometry and culture. Methanogens present in the human digestive tract play major roles, in particular the use of hydrogen from the fermentation products of bacteria, thus promoting digestion. They are also involved in the transformation of heavy metals and in the use of trimethylamine produced by intestinal bacteria, thus preventing major health problems, in particular cardiovascular diseases. Several pieces of evidence suggest their close physical contacts with bacteria support symbiotic metabolism. Their imbalance during dysbiosis is associated with many pathologies in humans, particularly digestive tract diseases such as Crohn's disease, ulcerative colitis, diverticulosis, inflammatory bowel disease, irritable bowel syndrome, colonic polyposis, and colorectal cancer. There is a huge deficit of knowledge and partially contradictory information concerning human methanogens, so much remains to be done to fully understand their physiological role in humans. It is necessary to develop new methods for the identification and culture of methanogens from clinical samples. This will permit to isolate new methanogens species as well as their phenotypic characterization, to explore their genome by sequencing and to study the population dynamics of methanogens by specifying in particular their exact role within the complex flora associated with the mucous microbiota of human.
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Affiliation(s)
- C O Guindo
- IHU Méditerranée Infection, Marseille, France; Aix-Marseille Univ., IRD, MEPHI, IHU Méditerranée Infection, Marseille, France
| | - M Drancourt
- IHU Méditerranée Infection, Marseille, France
| | - G Grine
- Aix-Marseille Univ., IRD, MEPHI, IHU Méditerranée Infection, Marseille, France; Aix-Marseille Université, UFR Odontologie, Marseille, France.
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23
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Kim YJ, Paik CN, Lee JM, Kim DB, Yang JM. Acute gastric injury after ingestion of substrate with hyperosmolar glucose and benzoate inversely related with small intestinal bacterial overgrowth. TURKISH JOURNAL OF GASTROENTEROLOGY 2020; 31:425-432. [PMID: 32721913 DOI: 10.5152/tjg.2020.19112] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND/AIMS The occurrence of gastrointestinal symptoms and the presence of small intestinal bacterial overgrowth (SIBO) could be determined after ingestion of substrate with highly concentrated glucose for glucose breath test (GBT), after which endoscopic images for acute gastric injury have not been clarified. The aims of this study were to investigate the prevalence and relationship of acute gastric injury with SIBO after GBT. MATERIALS AND METHODS A cohort of 235 patients with functional gastrointestinal symptoms undergoing breath test with 50 g glucose solution, immediately followed by upper endoscopy were surveyed. The acute gastric injury in endoscopic images and the GBT for hydrogen (H2) or methane (CH4) were assessed. RESULTS The prevalence of acute gastric injury was 28.1% (66/235) after GBT. There were significant differences in GBT positivity (+) with and without gastric injury (25.8% vs 40.8%, p=0.03). In subtypes, GBT (H2) + was significantly lower in group with gastric injury than in the group without. No differences were seen in GBT (CH4) + between two groups. On multivariate analysis, the subtype of GBT (H2) + (Odds ratio (OR)=0.42; 95% Confidence interval (CI)=0.20-0.90; p=0.03) inversely and female (OR=2.11; 95% CI=1.11-4.00; p=0.02) were significantly related with gastric injury. Whereas gastric injury was the only independent related factor for GBT + inversely (OR=0.51; 95% CI=0.27-0.97; p=0.04). CONCLUSION Highly concentrated glucose might provoke acute gastric injury, which could predict the absence of SIBO.
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Affiliation(s)
- Yeon Ji Kim
- Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon School of Medicine, Republic of Korea
| | - Chang Nyol Paik
- Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon School of Medicine, Republic of Korea
| | - Ji-Min Lee
- Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon School of Medicine, Republic of Korea
| | - Dae Bum Kim
- Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon School of Medicine, Republic of Korea
| | - Jin Mo Yang
- Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon School of Medicine, Republic of Korea
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24
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Shah A, Talley NJ, Koloski N, Macdonald GA, Kendall BJ, Shanahan ER, Walker MM, Keely S, Jones MP, Morrison M, Holtmann GJ. Duodenal bacterial load as determined by quantitative polymerase chain reaction in asymptomatic controls, functional gastrointestinal disorders and inflammatory bowel disease. Aliment Pharmacol Ther 2020; 52:155-167. [PMID: 32412673 DOI: 10.1111/apt.15786] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2020] [Revised: 02/12/2020] [Accepted: 04/20/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Small intestinal bacterial overgrowth may play a role in gastrointestinal and non-gastrointestinal diseases. AIMS To use quantitative polymerase chain reaction (qPCR) to determine and compare bacterial loads of duodenal biopsies in asymptomatic controls, and patients with functional gastrointestinal disorders (FGIDs) and inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn's disease (CD). To define effects of gastric acid inhibition on bacterial load, explore links of bacterial load and gastrointestinal symptoms in response to a standardised nutrient challenge and compare bacterial load with glucose breath test results. METHODS In 237 patients (63 controls, 84 FGID and 90 IBD), we collected mucosal samples under aseptic conditions during endoscopy extracted and total DNA. Bacterial load metric was calculated utilising qPCR measurements of the bacterial 16S rRNA gene, normalised to human beta-actin expression. Standard glucose breath test and nutrient challenge test were performed. RESULTS The duodenal microbial load was higher in patients with FGID (0.22 ± 0.03) than controls (0.07 ± 0.05; P = 0.007) and patients with UC (0.01 ± 0.05) or CD (0.02 ± 0.09), (P = 0.0001). While patients treated with proton pump inhibitors (PPI) had significantly higher bacterial loads than non-users (P < 0.05), this did not explain differences between patient groups and controls. Bacterial load was significantly (r = 0.21, P < 0.016) associated with the symptom response to standardised nutrient challenge test. Methane, but not hydrogen values on glucose breath test were associated with bacterial load measured utilising qPCR. CONCLUSIONS Utilising qPCR, a diagnosis of FGID and treatment with PPI were independently associated with increased bacterial loads. Increased bacterial loads are associated with an augmented symptom response to a standardised nutrient challenge.
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Affiliation(s)
- Ayesha Shah
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Qld, Australia.,Faculty of Medicine and Faulty of Health and Behavioural Sciences, University of Queensland, Brisbane, Qld, Australia
| | - Nicholas J Talley
- Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, Australia
| | - Natasha Koloski
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Qld, Australia.,Faculty of Medicine and Faulty of Health and Behavioural Sciences, University of Queensland, Brisbane, Qld, Australia
| | - Graeme A Macdonald
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Qld, Australia.,Faculty of Medicine and Faulty of Health and Behavioural Sciences, University of Queensland, Brisbane, Qld, Australia
| | - Bradley J Kendall
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Qld, Australia.,Faculty of Medicine and Faulty of Health and Behavioural Sciences, University of Queensland, Brisbane, Qld, Australia
| | - Erin R Shanahan
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Qld, Australia.,Faculty of Medicine and Faulty of Health and Behavioural Sciences, University of Queensland, Brisbane, Qld, Australia
| | - Marjorie M Walker
- Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, Australia
| | - Simon Keely
- Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, Australia
| | - Michael P Jones
- Psychology Department, Macquarie University, Ryde, NSW, Australia
| | - Mark Morrison
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Qld, Australia.,Diamantina Institute, University of Queensland, Brisbane, Qld, Australia
| | - Gerald J Holtmann
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Qld, Australia.,Faculty of Medicine and Faulty of Health and Behavioural Sciences, University of Queensland, Brisbane, Qld, Australia
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Shah RM, McKenzie EJ, Rosin MT, Jadhav SR, Gondalia SV, Rosendale D, Beale DJ. An Integrated Multi-Disciplinary Perspectivefor Addressing Challenges of the Human Gut Microbiome. Metabolites 2020; 10:E94. [PMID: 32155792 PMCID: PMC7143645 DOI: 10.3390/metabo10030094] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Revised: 02/18/2020] [Accepted: 02/27/2020] [Indexed: 02/06/2023] Open
Abstract
Our understanding of the human gut microbiome has grown exponentially. Advances in genome sequencing technologies and metagenomics analysis have enabled researchers to study microbial communities and their potential function within the context of a range of human gut related diseases and disorders. However, up until recently, much of this research has focused on characterizing the gut microbiological community structure and understanding its potential through system wide (meta) genomic and transcriptomic-based studies. Thus far, the functional output of these microbiomes, in terms of protein and metabolite expression, and within the broader context of host-gut microbiome interactions, has been limited. Furthermore, these studies highlight our need to address the issues of individual variation, and of samples as proxies. Here we provide a perspective review of the recent literature that focuses on the challenges of exploring the human gut microbiome, with a strong focus on an integrated perspective applied to these themes. In doing so, we contextualize the experimental and technical challenges of undertaking such studies and provide a framework for capitalizing on the breadth of insight such approaches afford. An integrated perspective of the human gut microbiome and the linkages to human health will pave the way forward for delivering against the objectives of precision medicine, which is targeted to specific individuals and addresses the issues and mechanisms in situ.
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Affiliation(s)
- Rohan M. Shah
- Department of Chemistry and Biotechnology, Faculty of Science, Engineering and Technology, Swinburne University of Technology, Hawthorn, VIC 3122, Australia;
- Land and Water, Commonwealth Scientific and Industrial Research Organization (CSIRO), Dutton Park, QLD 4102, Australia
| | - Elizabeth J. McKenzie
- Liggins Institute, The University of Auckland, Grafton, Auckland 1142, New Zealand; (E.J.M.); (M.T.R.)
| | - Magda T. Rosin
- Liggins Institute, The University of Auckland, Grafton, Auckland 1142, New Zealand; (E.J.M.); (M.T.R.)
| | - Snehal R. Jadhav
- Centre for Advanced Sensory Science, School of Exercise and Nutrition Sciences, Deakin University, Burwood, VIC 3125, Australia;
| | - Shakuntla V. Gondalia
- Centre for Human Psychopharmacology, Swinburne University of Technology, Hawthorn, VIC 3122, Australia;
| | | | - David J. Beale
- Land and Water, Commonwealth Scientific and Industrial Research Organization (CSIRO), Dutton Park, QLD 4102, Australia
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Human beings as islands of stability: Monitoring body states using breath profiles. Sci Rep 2019; 9:16167. [PMID: 31700057 PMCID: PMC6838060 DOI: 10.1038/s41598-019-51417-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Accepted: 09/26/2019] [Indexed: 02/06/2023] Open
Abstract
By checking the reproducibility of conventional mid-infrared Fourier spectroscopy of human breath in a small test study (15 individuals), we found that a set of volatile organic compounds (VOC) of the individual breath samples remains reproducible at least for 18 months. This set forms a unique individual’s “island of stability” (IOS) in a multidimensional VOC concentration space. The IOS stability can simultaneously be affected by various life effects as well as the onset of a disease. Reflecting the body state, they both should have different characteristics. Namely, they could be distinguished by different temporal profiles: In the case of life effects (beverage intake, physical or mental exercises, smoking etc.), there is a non-monotonic shift of the IOS position with the return to the steady state, whereas a progressing disease corresponds to a monotonic IOS shift. As a first step of proving these dependencies, we studied various life effects with the focus on the strength and characteristic time of the IOS shift. In general, our results support homeostasis on a long time scale of months, allostasis on scales of hours to weeks or until smoke quitting for smokers, as well as resilience in the case of recovery from a disease.
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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: 71] [Impact Index Per Article: 11.8] [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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Wilder-Smith CH, Olesen SS, Materna A, Drewes AM. Fermentable Sugar Ingestion, Gas Production, and Gastrointestinal and Central Nervous System Symptoms in Patients With Functional Disorders. Gastroenterology 2018; 155:1034-1044.e6. [PMID: 30009815 DOI: 10.1053/j.gastro.2018.07.013] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2017] [Revised: 06/03/2018] [Accepted: 07/03/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS Functional gastrointestinal disorders (FGID) are defined by broad phenotypic descriptions and exclusion of recognizable disease. FGIDs cause multi-organ symptoms and abnormal results in a wide range of laboratory tests, indicating broad mechanisms of pathogenesis. Many patients with FGID develop symptoms following ingestion of fermentable sugars; we investigated the associations between symptoms and intestinal gas production following sugar provocation tests to elucidate mechanisms of FGID. METHODS We performed fructose and lactose breath tests in 2042 patients with a diagnosis of FGID (based on Rome III criteria), referred to a gastroenterology practice from January 2008 through December 2011. Medical and diet histories were collected from all subjects. Breath samples were collected before and each hour after, for 5 hours, subjects ingested fructose (35 g) and lactose (50 g) dissolved in 300 mL water. Hydrogen and methane gas concentrations were measured and GI and non-GI symptoms were registered for 5 hours following sugar ingestion. Symptom and gas time profiles were compared, treelet transforms were used to derive data-related symptom clusters, and the symptom severity of the clusters were analyzed for their association with breath gas characteristics. RESULTS We identified 11 GI and central nervous system (CNS) symptom profiles and hydrogen and methane breath concentrations that changed significantly with time following sugar ingestion. Treelet transform analysis identified 2 distinct clusters, based on GI and CNS symptoms. The severity scores for the GI and CNS symptoms correlated following ingestion of sugars (all, P < .0001). However, only the GI symptoms associated with hydrogen and methane gas production (all, P < .0001). CONCLUSIONS In an analysis of breath test results from more than 2000 patients with FGIDs, we identified clusters of GI and CNS symptoms in response to fructose of lactose ingestion. The association between specific symptoms and breath gas concentrations indicate distinct mechanisms of FGID pathogenesis, such as changes in the microbiome or mechanical and chemical sensitization. ClinicalTrials.gov ID: NCT02085889.
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Affiliation(s)
| | - Søren S Olesen
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Andrea Materna
- Brain-Gut Research Group, Gastroenterology Group Practice, Bern, Switzerland
| | - Asbjørn M Drewes
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
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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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Sieczkowska A, Landowski P, Gibas A, Kamińska B, Lifschitz C. Long-term proton pump inhibitor therapy leads to small bowel bacterial overgrowth as determined by breath hydrogen and methane excretion. J Breath Res 2018; 12:036006. [DOI: 10.1088/1752-7163/aa9dcf] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Laverdure R, Mezouari A, Carson MA, Basiliko N, Gagnon J. A role for methanogens and methane in the regulation of GLP-1. Endocrinol Diabetes Metab 2018; 1:e00006. [PMID: 30815543 PMCID: PMC6353219 DOI: 10.1002/edm2.6] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2017] [Revised: 10/24/2017] [Accepted: 10/29/2017] [Indexed: 12/20/2022] Open
Abstract
INTRODUCTION The gastrointestinal (GI) microbiome has emerged as a potential regulator of metabolism. However, the precise mechanisms of how microorganisms may influence physiology remain largely unknown. Interestingly, GI microorganisms, including methanogens, are localized within the same regions as the glucagon-like peptide-1 (GLP-1) secreting L cells. GLP-1 plays key roles appetite and glucose regulation. Furthermore, both methane and GLP-1 levels are altered in obese humans with metabolic disease. We predict that high-fat diet-induced obesity alters the abundance of GI methanogens and that methane may play a role in the GLP-1 secretory response from the L cell. METHODS To demonstrate this, GLP-1 secretion response and faecal methanogens were examined in mice given a high-fat diet for 14 weeks. In addition, the direct effect of methane on GLP-1 secretion was assessed in two L-cell models (NCI-H716 and GLUTag). RESULTS High-fat diet caused a significant increase in both GLP-1 secretion and faecal methanogen content. There was a direct correlation between GLP-1 secretion response and faecal methanogen levels. In L cells, methane stimulated GLP-1 secretion and enhanced intracellular cAMP content. CONCLUSION These results indicate that alterations in the methanogen communities occurring in obesity may play a vital role in directly enhancing GLP-1 secretion, and that methane can directly stimulate the secretion of GLP-1.
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Affiliation(s)
- Rose Laverdure
- Department of BiologyLaurentian UniversitySudburyONCanada
| | - Ania Mezouari
- Department of BiologyLaurentian UniversitySudburyONCanada
| | - Michael A. Carson
- Department of BiologyLaurentian UniversitySudburyONCanada
- Vale Living with Lakes CentreLaurentian UniversitySudburyONCanada
| | - Nathan Basiliko
- Department of BiologyLaurentian UniversitySudburyONCanada
- Vale Living with Lakes CentreLaurentian UniversitySudburyONCanada
| | - Jeffrey Gagnon
- Department of BiologyLaurentian UniversitySudburyONCanada
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Lee JM, Paik CN, Kim YJ, Kim DB, Chung WC, Lee KM, Yang JM. The association between a positive lactulose methane breath test and rectocele in constipated patients. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2017; 110:115-122. [PMID: 29271223 DOI: 10.17235/reed.2017.5017/2017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
OBJECTIVES Rectocele with constipation might be related to methane (CH4) producing intestinal bacteria. We investigated the breath CH4 levels and the clinical characteristics of colorectal motility in constipated patients with rectocele. METHODS A database of consecutive female outpatients was reviewed for the evaluation of constipation according to the Rome III criteria. The patients underwent the lactulose CH4 breath test (LMBT), colon marker study, anorectal manometry, defecography and bowel symptom questionnaire. The profiles of the lactulose breath test (LBT) in 33 patients with rectocele (with size ≥ 2 cm) and 26 patients with functional constipation (FC) were compared with the breath test results of 30 healthy control subjects. RESULTS The mean size of rectocele was 3.52 ± 1.06 cm. The rate of a positive LMBT (LMBT+) was significantly higher in patients with rectocele (33.3%) than in those with FC (23.1%) or healthy controls (6.7%) (p = 0.04). Breath CH4 concentration was positively correlated with rectosigmoid colon transit time in rectocele patients (γ = 0.481, p < 0.01). A maximum high pressure zone pressure > 155 mmHg was a significant independent factor of LMBT+ in rectocele patients (OR = 8.93, 95% CI = 1.14-71.4, p = 0.04). CONCLUSIONS LMBT+ might be expected in constipated patients with rectocele. Moreover, increased rectosigmoid colonic transit or high anorectal pressure might be associated with CH4 breath levels. Breath CH4 could be an important therapeutic target for managing constipated patients with rectocele.
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Affiliation(s)
- Ji Min Lee
- College of Medicine, St. Vincent's Hospital, The Catholic University of Korea
| | - Chang Nyol Paik
- Internal Medicine, , St. Vincent's Hospital, College of Medicine, Th, South Korea
| | - Yeon Ji Kim
- Division of Gastroenterology, Department of Internal Medicine, St. Vincent's Hospital, The Catholic
| | - Dae Bum Kim
- St. Vincent's Hospital, College of Medicine, The Catholic University of Korea
| | - Woo Chul Chung
- St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Republic of Ko
| | - Kang-Moon Lee
- St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Republic of Ko
| | - Jin-Mo Yang
- , College of Medicine, St. Vincent's Hospital, The Catholic University of Korea
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Cummins G, Yung DE, Cox BF, Koulaouzidis A, Desmulliez MPY, Cochran S. Luminally expressed gastrointestinal biomarkers. Expert Rev Gastroenterol Hepatol 2017; 11:1119-1134. [PMID: 28849686 DOI: 10.1080/17474124.2017.1373017] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
A biomarker is a measurable indicator of normal biologic processes, pathogenic processes or pharmacological responses. The identification of a useful biomarker is challenging, with several hurdles to overcome before clinical adoption. This review gives a general overview of a range of biomarkers associated with inflammatory bowel disease or colorectal cancer along the gastrointestinal tract. Areas covered: These markers include those that are already clinically accepted, such as inflammatory markers such as faecal calprotectin, S100A12 (Calgranulin C), Fatty Acid Binding Proteins (FABP), malignancy markers such as Faecal Occult Blood, Mucins, Stool DNA, Faecal microRNA (miRNA), other markers such as Faecal Elastase, Faecal alpha-1-antitrypsin, Alpha2-macroglobulin and possible future markers such as microbiota, volatile organic compounds and pH. Expert commentary: There are currently a few biomarkers that have been sufficiently validated for routine clinical use at present such as FC. However, many of these biomarkers continue to be limited in sensitivity and specificity for various GI diseases. Emerging biomarkers have the potential to improve diagnosis and monitoring but further study is required to determine efficacy and validate clinical utility.
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Affiliation(s)
- Gerard Cummins
- a Institute of Sensors, Signals and Systems, School of Engineering and Physical Sciences , Heriot-Watt University , Edinburgh , UK
| | - Diana E Yung
- b The Royal Infirmary of Edinburgh , Endoscopy Unit , Edinburgh , UK
| | - Ben F Cox
- c School of Medicine , University of Dundee , Dundee , UK
| | | | - Marc P Y Desmulliez
- a Institute of Sensors, Signals and Systems, School of Engineering and Physical Sciences , Heriot-Watt University , Edinburgh , UK
| | - Sandy Cochran
- d Medical and Industrial Ultrasonics, School of Engineering , University of Glasgow , Glasgow , UK
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Hubert S, Chadwick A, Wacher V, Coughlin O, Kokai-Kun J, Bristol A. Development of a Modified-Release Formulation of Lovastatin Targeted to Intestinal Methanogens Implicated in Irritable Bowel Syndrome With Constipation. J Pharm Sci 2017; 107:662-671. [PMID: 28989013 DOI: 10.1016/j.xphs.2017.09.028] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2017] [Revised: 09/18/2017] [Accepted: 09/19/2017] [Indexed: 12/19/2022]
Abstract
There is growing evidence that methane production, predominantly by Methanobrevibacter smithii, in the intestines is a cause of constipation, pain, and bloating in irritable bowel syndrome with constipation (IBS-C). M smithii resides primarily in the large intestine but can also colonize the small intestine. In vitro studies found that the prodrug lactone form of lovastatin, found in cholesterol-lowering drugs, inhibited methane production in stool samples from patients with IBS-C. However, the cholesterol-lowering lovastatin β-hydroxyacid was ineffective at inhibiting methane production in this system. A considerable amount of lovastatin is converted to hydroxyacid in the stomach and is absorbed. It was hypothesized that galenic innovations could protect lovastatin from the stomach and allow release in 2 strategic locations, the duodenum and the ileocecal region, to reach M smithii. The desired release profile was achieved by developing an oral dosage form containing lovastatin and coated with 2 different enteric polymers that enabled a pH-dependent "dual pulse" drug release. Combinations of the 2 coated tablets were encapsulated together to deliver the desired amount of lovastatin to the targeted intestinal locations. The capsules have been tested in vitro and in vivo and show promise in treating IBS-C.
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Affiliation(s)
- Steven Hubert
- Synthetic Biologics, Inc., 9605 Medical Center Drive, Suite 270, Rockville, Maryland 20850.
| | - Alan Chadwick
- Aesica Formulation Development, Biocity, Pennyfoot Street, Nottingham NG1 1GF, UK
| | - Vince Wacher
- Synthetic Biologics, Inc., 9605 Medical Center Drive, Suite 270, Rockville, Maryland 20850
| | - Olivia Coughlin
- Synthetic Biologics, Inc., 9605 Medical Center Drive, Suite 270, Rockville, Maryland 20850
| | - John Kokai-Kun
- Synthetic Biologics, Inc., 9605 Medical Center Drive, Suite 270, Rockville, Maryland 20850
| | - Andrew Bristol
- Synthetic Biologics, Inc., 9605 Medical Center Drive, Suite 270, Rockville, Maryland 20850
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Tomasova L, Konopelski P, Ufnal M. Gut Bacteria and Hydrogen Sulfide: The New Old Players in Circulatory System Homeostasis. Molecules 2016; 21:E1558. [PMID: 27869680 PMCID: PMC6273628 DOI: 10.3390/molecules21111558] [Citation(s) in RCA: 112] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2016] [Revised: 10/31/2016] [Accepted: 11/14/2016] [Indexed: 12/16/2022] Open
Abstract
Accumulating evidence suggests that gut bacteria play a role in homeostasis of the circulatory system in mammals. First, gut bacteria may affect the nervous control of the circulatory system via the sensory fibres of the enteric nervous system. Second, gut bacteria-derived metabolites may cross the gut-blood barrier and target blood vessels, the heart and other organs involved in the regulation of the circulatory system. A number of studies have shown that hydrogen sulfide (H₂S) is an important biological mediator in the circulatory system. Thus far, research has focused on the effects of H₂S enzymatically produced by cardiovascular tissues. However, some recent evidence indicates that H₂S released in the colon may also contribute to the control of arterial blood pressure. Incidentally, sulfate-reducing bacteria are ubiquitous in mammalian colon, and H₂S is just one among a number of molecules produced by the gut flora. Other gut bacteria-derived compounds that may affect the circulatory system include methane, nitric oxide, carbon monoxide, trimethylamine or indole. In this paper, we review studies that imply a role of gut microbiota and their metabolites, such as H₂S, in circulatory system homeostasis.
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Affiliation(s)
- Lenka Tomasova
- Department of Experimental Physiology and Pathophysiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw 02 091, Poland.
- Institute of Clinical and Translational Research, Biomedical Research Center, Slovak Academy of Sciences, Bratislava 845 05, Slovakia.
| | - Piotr Konopelski
- Department of Experimental Physiology and Pathophysiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw 02 091, Poland.
| | - Marcin Ufnal
- Department of Experimental Physiology and Pathophysiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw 02 091, Poland.
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Ou JZ, Cottrell JJ, Ha N, Pillai N, Yao CK, Berean KJ, Ward SA, Grando D, Muir JG, Harrison CJ, Wijesiriwardana U, Dunshea FR, Gibson PR, Kalantar-zadeh K. Potential of in vivo real-time gastric gas profiling: a pilot evaluation of heat-stress and modulating dietary cinnamon effect in an animal model. Sci Rep 2016; 6:33387. [PMID: 27633400 PMCID: PMC5025890 DOI: 10.1038/srep33387] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2016] [Accepted: 08/24/2016] [Indexed: 01/12/2023] Open
Abstract
Gastroenterologists are still unable to differentiate between some of the most ordinary disorders of the gut and consequently patients are misdiagnosed. We have developed a swallowable gas sensor capsule for addressing this. The gases of the gut are the by-product of the fermentation processes during digestion, affected by the gut state and can consequently provide the needed information regarding the health of the gut. Here we present the first study on gas sensor capsules for revealing the effect of a medical supplement in an animal (pig) model. We characterise the real-time alterations of gastric-gas in response to environmental heat-stress and dietary cinnamon and use the gas profiles for understanding the bio-physiological changes. Under no heat-stress, feeding increases gastric CO2 concentration, while dietary cinnamon reduces it due to decrease in gastric acid and pepsin secretion. Alternatively, heat-stress leads to hyperventilation in pigs, which reduces CO2 concentration and with the cinnamon treatment, CO2 diminishes even more, resulting in health improvement outcomes. Overall, a good repeatability in gas profiles is also observed. The model demonstrates the strong potential of real-time gas profiler in providing new physiological information that will impact understanding of therapeutics, presenting a highly reliable device for monitoring/diagnostics of gastrointestinal disorders.
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Affiliation(s)
- Jian Zhen Ou
- School of Engineering, RMIT University, Melbourne, Australia
| | - Jeremy J. Cottrell
- Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Australia
| | - Nam Ha
- School of Engineering, RMIT University, Melbourne, Australia
| | - Naresh Pillai
- School of Engineering, RMIT University, Melbourne, Australia
| | - Chu K. Yao
- Department of Gastroenterology, The Alfred Hospital, Monash University, Melbourne, Australia
| | - Kyle J. Berean
- School of Engineering, RMIT University, Melbourne, Australia
| | - Stephanie A. Ward
- Monash Ageing Research Centre, Monash University, Melbourne, Australia
| | | | - Jane G. Muir
- Department of Gastroenterology, The Alfred Hospital, Monash University, Melbourne, Australia
| | | | - Udani Wijesiriwardana
- Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Australia
| | - Frank R. Dunshea
- Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Australia
| | - Peter R. Gibson
- Department of Gastroenterology, The Alfred Hospital, Monash University, Melbourne, Australia
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Siddiqui I, Ahmed S, Abid S. Update on diagnostic value of breath test in gastrointestinal and liver diseases. World J Gastrointest Pathophysiol 2016; 7:256-265. [PMID: 27574563 PMCID: PMC4981765 DOI: 10.4291/wjgp.v7.i3.256] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2016] [Revised: 04/22/2016] [Accepted: 05/10/2016] [Indexed: 02/06/2023] Open
Abstract
In the field of gastroenterology, breath tests (BTs) are used intermittently as diagnostic tools that allow indirect, non-invasive and relatively less cumbersome evaluation of several disorders by simply quantifying the appearance in exhaled breath of a metabolite of a specific substrate administered. The aim of this review is to have an insight into the principles, methods of analysis and performance parameters of various hydrogen, methane and carbon BTs which are available for diagnosing gastrointestinal disorders such as Helicobacter pylori infection, small intestinal bacterial overgrowth, and carbohydrate malabsorption. Evaluation of gastric emptying is routinely performed by scintigraphy which is however, difficult to perform and not suitable for children and pregnant women, this review has abridged the 13C-octanoic acid test in comparison to scintigraphy and has emphasized on its working protocol and challenges. A new development such as electronic nose test is also highlighted. Moreover we have also explored the limitations and constraints restraining the wide use of these BT. We conclude that breath testing has an enormous potential to be used as a diagnostic modality. In addition it offers distinct advantages over the traditional invasive methods commonly employed.
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Alterations of the human gut microbiome in multiple sclerosis. Nat Commun 2016; 7:12015. [PMID: 27352007 PMCID: PMC4931233 DOI: 10.1038/ncomms12015] [Citation(s) in RCA: 923] [Impact Index Per Article: 102.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2015] [Accepted: 05/20/2016] [Indexed: 02/07/2023] Open
Abstract
The gut microbiome plays an important role in immune function and has been implicated in several autoimmune disorders. Here we use 16S rRNA sequencing to investigate the gut microbiome in subjects with multiple sclerosis (MS, n=60) and healthy controls (n=43). Microbiome alterations in MS include increases in Methanobrevibacter and Akkermansia and decreases in Butyricimonas, and correlate with variations in the expression of genes involved in dendritic cell maturation, interferon signalling and NF-kB signalling pathways in circulating T cells and monocytes. Patients on disease-modifying treatment show increased abundances of Prevotella and Sutterella, and decreased Sarcina, compared with untreated patients. MS patients of a second cohort show elevated breath methane compared with controls, consistent with our observation of increased gut Methanobrevibacter in MS in the first cohort. Further study is required to assess whether the observed alterations in the gut microbiome play a role in, or are a consequence of, MS pathogenesis. The gut microbiome has been implicated in several autoimmune disorders. Here, the authors study the gut microbiome of patients with multiple sclerosis, and find correlations between altered abundance of certain gut microorganisms and changes in expression of immune defence genes.
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Abstract
Obesity constitutes a significant and rapidly increasing public health challenge and is associated with significant co-morbidities and healthcare costs. Although undoubtedly multifactorial, research over the last decade has demonstrated that the microbes that colonize the human gut may contribute to the development of obesity through roles in polysaccharide breakdown, nutrient absorption, inflammatory responses and gut permeability. Studies have consistently shown that the Firmicutes to Bacteroidetes ratio, in particular, is increased in obesity and reduces with weight loss. In addition, we and others have shown that the methanogenic Archaea may also contribute to altered metabolism and weight gain in the host. However, much remains to be learned about the roles of different gut microbial populations in weight gain and obesity and the underlying mechanisms before we can begin to approach targeted treatments.
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Affiliation(s)
- Ruchi Mathur
- Division of Endocrine Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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Vendl C, Clauss M, Stewart M, Leggett K, Hummel J, Kreuzer M, Munn A. Decreasing methane yield with increasing food intake keeps daily methane emissions constant in two foregut fermenting marsupials, the western grey kangaroo and red kangaroo. J Exp Biol 2015; 218:3425-34. [DOI: 10.1242/jeb.128165] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
ABSTRACT
Fundamental differences in methane (CH4) production between macropods (kangaroos) and ruminants have been suggested and linked to differences in the composition of the forestomach microbiome. Using six western grey kangaroos (Macropus fuliginosus) and four red kangaroos (Macropus rufus), we measured daily absolute CH4 production in vivo as well as CH4 yield (CH4 per unit of intake of dry matter, gross energy or digestible fibre) by open-circuit respirometry. Two food intake levels were tested using a chopped lucerne hay (alfalfa) diet. Body mass-specific absolute CH4 production resembled values previously reported in wallabies and non-ruminant herbivores such as horses, and did not differ with food intake level, although there was no concomitant proportionate decrease in fibre digestibility with higher food intake. In contrast, CH4 yield decreased with increasing intake, and was intermediate between values reported for ruminants and non-ruminant herbivores. These results correspond to those in ruminants and other non-ruminant species where increased intake (and hence a shorter digesta retention in the gut) leads to a lower CH4 yield. We hypothesize that rather than harbouring a fundamentally different microbiome in their foregut, the microbiome of macropods is in a particular metabolic state more tuned towards growth (i.e. biomass production) rather than CH4 production. This is due to the short digesta retention time in macropods and the known distinct ‘digesta washing’ in the gut of macropods, where fluids move faster than particles and hence most likely wash out microbes from the forestomach. Although our data suggest that kangaroos only produce about 27% of the body mass-specific volume of CH4 of ruminants, it remains to be modelled with species-specific growth rates and production conditions whether or not significantly lower CH4 amounts are emitted per kg of meat in kangaroo than in beef or mutton production.
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Affiliation(s)
- Catharina Vendl
- Clinic for Zoo Animals, Exotic Pets and Wildlife, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland
- Centre for Sustainable Ecosystems Solutions, School of Biological Sciences, University of Wollongong, Wollongong, NSW 2522, Australia
| | - Marcus Clauss
- Clinic for Zoo Animals, Exotic Pets and Wildlife, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland
| | - Mathew Stewart
- Centre for Sustainable Ecosystems Solutions, School of Biological Sciences, University of Wollongong, Wollongong, NSW 2522, Australia
| | - Keith Leggett
- Fowlers Gap Arid Zone Research Station, School of Biological, Earth and Environmental Sciences, University of New South Wales, Fowlers Gap, Broken Hill, NSW 2880, Australia
| | - Jürgen Hummel
- Department of Animal Sciences, Ruminant Nutrition, University of Göttingen, 37077 Göttingen, Germany
| | - Michael Kreuzer
- ETH Zurich, Institute of Agricultural Sciences, 8092 Zurich, Switzerland
| | - Adam Munn
- Centre for Sustainable Ecosystems Solutions, School of Biological Sciences, University of Wollongong, Wollongong, NSW 2522, Australia
- Fowlers Gap Arid Zone Research Station, School of Biological, Earth and Environmental Sciences, University of New South Wales, Fowlers Gap, Broken Hill, NSW 2880, Australia
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41
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Barlow GM, Yu A, Mathur R. Role of the Gut Microbiome in Obesity and Diabetes Mellitus. Nutr Clin Pract 2015; 30:787-97. [PMID: 26452391 DOI: 10.1177/0884533615609896] [Citation(s) in RCA: 175] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Type 2 diabetes mellitus (T2DM) and obesity represent two of the biggest global health challenges of this century and are associated with significant comorbidities and healthcare costs. Although multiple factors undoubtedly contribute to the development and progression of DM and obesity, research over the last decade has demonstrated that the microbes that colonize the human gut may play key contributory roles. Gut microbes are now known to codevelop with the human host and are strongly influenced by mode of birth and early diet and nutrition, as well as environmental and other factors including antibiotic exposure. Gut microbes contribute to human health through roles in polysaccharide breakdown, nutrient absorption, inflammatory responses, gut permeability, and bile acid modification. Numerous studies have suggested that disruptions in the relative proportions of gut microbial populations may contribute to weight gain and insulin resistance, including alterations in Gammaproteobacteria and Verrucomicrobia and the ratios of Firmicutes to Bacteroidetes in weight gain and possible alterations in butyrate-producing bacteria such as Faecalibacterium prausnitzii in DM. In addition, it has been shown that the methanogenic Archaea may contribute to altered metabolism and weight gain in the host. However, the majority of studies are performed with stool or colonic samples and may not be representative of the metabolically active small intestine. Studies predominantly in rodent models are beginning to elucidate the mechanisms by which gut microbes contribute to DM and obesity, but much remains to be learned before we can begin to approach targeted treatments.
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Affiliation(s)
- Gillian M Barlow
- GI Motility Program, Cedars-Sinai Medical Center, Los Angeles, California
| | - Allen Yu
- GI Motility Program, Cedars-Sinai Medical Center, Los Angeles, California
| | - Ruchi Mathur
- Division of Endocrine Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, California
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Houben E, De Preter V, Billen J, Van Ranst M, Verbeke K. Additional Value of CH₄ Measurement in a Combined (13)C/H₂ Lactose Malabsorption Breath Test: A Retrospective Analysis. Nutrients 2015; 7:7469-85. [PMID: 26371034 PMCID: PMC4586543 DOI: 10.3390/nu7095348] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2015] [Revised: 08/31/2015] [Accepted: 09/01/2015] [Indexed: 12/18/2022] Open
Abstract
The lactose hydrogen breath test is a commonly used, non-invasive method for the detection of lactose malabsorption and is based on an abnormal increase in breath hydrogen (H2) excretion after an oral dose of lactose. We use a combined 13C/H2 lactose breath test that measures breath 13CO2 as a measure of lactose digestion in addition to H2 and that has a better sensitivity and specificity than the standard test. The present retrospective study evaluated the results of 1051 13C/H2 lactose breath tests to assess the impact on the diagnostic accuracy of measuring breath CH4 in addition to H2 and 13CO2. Based on the 13C/H2 breath test, 314 patients were diagnosed with lactase deficiency, 138 with lactose malabsorption or small bowel bacterial overgrowth (SIBO), and 599 with normal lactose digestion. Additional measurement of CH4 further improved the accuracy of the test as 16% subjects with normal lactose digestion and no H2-excretion were found to excrete CH4. These subjects should have been classified as subjects with lactose malabsorption or SIBO. In conclusion, measuring CH4-concentrations has an added value to the 13C/H2 breath test to identify methanogenic subjects with lactose malabsorption or SIBO.
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Affiliation(s)
- Els Houben
- Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven 3000, Belgium.
- Clinical Department of Laboratory Medicine, University Hospitals Leuven, Leuven 3000, Belgium.
| | - Vicky De Preter
- Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven 3000, Belgium.
- Group Health and Social Work, University College Leuven-Limburg (UCLL), Leuven 3000, Belgium.
| | - Jaak Billen
- Clinical Department of Laboratory Medicine, University Hospitals Leuven, Leuven 3000, Belgium.
| | - Marc Van Ranst
- Clinical Department of Laboratory Medicine, University Hospitals Leuven, Leuven 3000, Belgium.
- Laboratory of Clinical and Epidemiological Virology, KU Leuven, Leuven 3000, Belgium.
| | - Kristin Verbeke
- Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven 3000, Belgium.
- Leuven Food Science and Nutrition Research Centre (LFoRCe), Leuven 3000, Belgium.
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43
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Park SY, Park HB, Lee JM, Lee HJ, Park CH, Kim HS, Choi SK, Rew JS. Relevance of Colonic Gas Analysis and Transit Study in Patients With Chronic Constipation. J Neurogastroenterol Motil 2015; 21:433-9. [PMID: 26058876 PMCID: PMC4496912 DOI: 10.5056/jnm14109] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2014] [Revised: 12/21/2014] [Accepted: 12/30/2014] [Indexed: 12/13/2022] Open
Abstract
Background/Aims Colon transit time (CTT) is a useful diagnostic tool in chronic constipation, but requires good patient compliance. We analyzed the correlation between the gas volume score (GVS) and CTT in patients with chronic constipation. Methods The study included 145 consecutive patients (65 men) with chronic constipation. The primary outcome was the correlation between the colon GVS and CTT. Secondary outcomes were the differences in colon GVS according to CTT and subtypes of chronic constipation. Results There were 81 patients with “CTT < 45 hours” and 64 patients with “CTT ≥ 45 hours.” In addition, 88 patients were classified as having functional constipation and 57 were classified as having constipation predominant irritable bowel syndrome (IBS-C). There was no significant correlation between CTT and colon GVS. However, the right colon GVS showed a positive correlation with right CTT (r = 0.255, P = 0.007). The median total colon GVS was significantly higher in patients with “CTT ≥ 45 hours” than in those with “CTT < 45 hours” (5.65% vs 4.15%, P = 0.010). There were no significant differences in colon GVS between the functional constipation and IBS-C. Conclusions We were unable to detect a correlation between GVS and CTT in patients with chronic constipation. However, total colon GVS may be a method of predicting slow transit in patients with chronic constipation.
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Affiliation(s)
- Seon-Young Park
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Hyun-Bum Park
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Ji-Myung Lee
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Ho-Jun Lee
- 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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Lurie-Weinberger MN, Gophna U. Archaea in and on the Human Body: Health Implications and Future Directions. PLoS Pathog 2015; 11:e1004833. [PMID: 26066650 PMCID: PMC4466265 DOI: 10.1371/journal.ppat.1004833] [Citation(s) in RCA: 85] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- Mor N. Lurie-Weinberger
- Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel
| | - Uri Gophna
- Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel
- * E-mail:
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45
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Di Stefano M, Mengoli C, Bergonzi M, Klersy C, Pagani E, Miceli E, Corazza GR. Breath Methane Excretion Is not An Accurate Marker of Colonic Methane Production in Irritable Bowel Syndrome. Am J Gastroenterol 2015; 110:891-8. [PMID: 25803403 DOI: 10.1038/ajg.2015.47] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2014] [Accepted: 01/29/2015] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The role of colonic methane production in functional bowel disorders is still uncertain. In small samples of irritable bowel syndrome (IBS) patients, it was shown that methane breath excretion correlates with clinical presentation and delayed gastrointestinal transit time. The aim of this study was to evaluate the relationship between intestinal production and breath excretion of CH4 and to correlate CH4 production with the presence and the severity of symptoms, in a large cohort of IBS patients and in a group of healthy volunteers. METHODS A group of 103 IBS patients and a group of 28 healthy volunteers were enrolled. The presence and severity of symptoms and gastrointestinal transit were evaluated in all subjects, who underwent breath H2/CH4 measurement for 7 h after lactulose to identify breath excretors of these gases; H2 and CH4 were also measured in rectal samples to identify colonic producers. Cumulative H2 and CH4 excretion and production were evaluated by the area under the time-concentration curve calculation (AUC). RESULTS In IBS patients, CH4 was detected in rectal samples in 48 patients (47%), but only 27 of them (26% of the 103 enrolled patients) excreted this gas with breath. In CH4 producers, the prevalence and severity of symptoms and gastrointestinal transit time were not significantly different with respect to non-producers. IBS subtypes were homogeneously represented in CH4 producers and in non-producers. Healthy volunteers, compared with IBS patients, showed a significantly lower prevalence of CH4 excretion, whereas no difference was found in the prevalence of colonic CH4 production; moreover, in healthy volunteers compared with IBS, CH4 breath excretion and CH4 production were not different in quantitative terms. CONCLUSION Our data show that colonic CH4 production is not associated with clinical presentation in IBS patients and does not correlate with symptom severity or with gastrointestinal transit time. Clinical inferences based on breath CH4 excretion should undergo an in-depth revision, as this method is not a good marker of CH4 colonic production.
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Affiliation(s)
- Michele Di Stefano
- 1st Department of Medicine, University of Pavia Foundation IRCCS "S. Matteo" Hospital, Pavia, Italy
| | - Caterina Mengoli
- 1st Department of Medicine, University of Pavia Foundation IRCCS "S. Matteo" Hospital, Pavia, Italy
| | - Manuela Bergonzi
- 1st Department of Medicine, University of Pavia Foundation IRCCS "S. Matteo" Hospital, Pavia, Italy
| | - Catherine Klersy
- Biometry and Clinical Epidemiology, Foundation IRCCS "S. Matteo" Hospital, Pavia, Italy
| | - Elisabetta Pagani
- 1st Department of Medicine, University of Pavia Foundation IRCCS "S. Matteo" Hospital, Pavia, Italy
| | - Emanuela Miceli
- 1st Department of Medicine, University of Pavia Foundation IRCCS "S. Matteo" Hospital, Pavia, Italy
| | - Gino Roberto Corazza
- 1st Department of Medicine, University of Pavia Foundation IRCCS "S. Matteo" Hospital, Pavia, Italy
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46
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Bang C, Schmitz RA. Archaea associated with human surfaces: not to be underestimated. FEMS Microbiol Rev 2015; 39:631-48. [DOI: 10.1093/femsre/fuv010] [Citation(s) in RCA: 64] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/05/2015] [Indexed: 12/18/2022] Open
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47
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Ou JZ, Yao CK, Rotbart A, Muir JG, Gibson PR, Kalantar-zadeh K. Human intestinal gas measurement systems: in vitro fermentation and gas capsules. Trends Biotechnol 2015; 33:208-213. [PMID: 25772639 DOI: 10.1016/j.tibtech.2015.02.002] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2014] [Revised: 01/29/2015] [Accepted: 02/03/2015] [Indexed: 12/16/2022]
Abstract
The biological and clinical significance of the human gut microbiome is currently attracting worldwide attention. While rRNA and DNA technologies led to a quantum leap in our understanding of the numbers and types of gut microorganisms, much less is known about these microorganisms' activity in situ and in real time. Accurately measuring their byproducts, including intestinal gases, may offer unique biomarkers for specific gut microbiota, accelerating our understanding of the relationships among intestinal gases, the metabolic activity of the gut microbiome, and human health states. Here we present two novel techniques, namely in vitro fermentation and gas capsule systems, for measuring and assessing selected gas species. We discuss new developments with these technologies and the methods of their implementation and provide an overall review of their operation.
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Affiliation(s)
- Jian Zhen Ou
- School of Electrical and Computer Engineering, RMIT University, Melbourne, Australia.
| | - C K Yao
- Department of Gastroenterology, The Alfred Hospital, Monash University, Melbourne, Australia
| | - Asaf Rotbart
- School of Electrical and Computer Engineering, RMIT University, Melbourne, Australia
| | - Jane G Muir
- Department of Gastroenterology, The Alfred Hospital, Monash University, Melbourne, Australia
| | - Peter R Gibson
- Department of Gastroenterology, The Alfred Hospital, Monash University, Melbourne, Australia
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Kurada S, Alkhouri N, Fiocchi C, Dweik R, Rieder F. Review article: breath analysis in inflammatory bowel diseases. Aliment Pharmacol Ther 2015; 41:329-41. [PMID: 25523187 DOI: 10.1111/apt.13050] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2014] [Revised: 05/15/2014] [Accepted: 11/21/2014] [Indexed: 12/13/2022]
Abstract
BACKGROUND There is an urgent need for cheap, reproducible, easy to perform and specific biomarkers for diagnosis, differentiation and stratification of inflammatory bowel disease (IBD) patients. Technical advances allow for the determination of volatile organic compounds in the human breath to differentiate between health and disease. AIM Review and discuss medical literature on volatile organic compounds in exhaled human breath in GI disorders, focusing on diagnosis and differentiation of IBD. METHODS A systematic search in PubMed, Ovid Medline and Scopus was completed using appropriate keywords. In addition, a bibliography search of each article was performed. RESULTS Mean breath pentane, ethane, propane, 1-octene, 3-methylhexane, 1-decene and NO levels were elevated (P < 0.05 to P < 10(-7)) and mean breath 1-nonene, (E)-2-nonene, hydrogen sulphide and methane were decreased in IBD compared to healthy controls (P = 0.003 to P < 0.001). A combined panel of 3 volatile organic compounds (octene, (E)-2-nonene and decene) showed the best discrimination between paediatric IBD and controls (AUC 0.96). Breath condensate cytokines were higher in IBD compared to healthy individuals (P < 0.008). Breath pentane, ethane, propane, isoprene and NO levels correlated with disease activity in IBD patients. Breath condensate interleukin-1β showed an inverse relation with clinical disease activity. CONCLUSIONS Breath analysis in IBD is a promising approach that is not yet ready for routine clinical use, but data from other gastrointestinal diseases suggest the feasibility for use of this technology in clinical practice. Well-designed future trials, incorporating the latest breath detection techniques, need to determine the exact breath metabolome pattern linked to diagnosis and phenotype of IBD.
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Affiliation(s)
- S Kurada
- Department of Hospital Medicine, Medicine Institute, Cleveland, OH, USA
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49
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Feng X, Su Y, Jiang J, Li N, Ding W, Wang Z, Hu X, Zhu W, Li J. Changes in Fecal and Colonic Mucosal Microbiota of Patients with Refractory Constipation after a Subtotal Colectomy. Am Surg 2015. [DOI: 10.1177/000313481508100235] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The purpose of this study was to investigate the changes in gut microbiota of patients with refractory constipation 6 months after a subtotal colectomy. Feces and mucosal samples of five healthy volunteers and 17 patients with refractory constipation before and six months after subtotal colectomy were collected. Denaturing gradient gel electrophoresis (DGGE) and polymerase chain reaction techniques were used for quantitative analysis of main bacterial groups and archeal methanogens. No significant differences were found in the DGGE profiles among the three groups. After subtotal colectomy, a significantly decreased similarity coefficient was observed in the fecal. The Shannon diversity indices had no significant differences among the three groups. The numbers of predominant bacteria (Bacteriodetes, Clostridium coccoides group, and Clostridium leptum group) did not significantly change in patients before and after surgery compared with healthy control subjects, and the number of total bacteria, Firmicutes, Bacteriodetes, and Clostridium leptum group bacteria in the feces decreased after surgery. However, the numbers of these bacteria remained the same in mucosa from postoperative patients. The numbers of Bifidobacteria and Lactobacilli in feces and the number of Bifidobacteria in mucosa were significantly lower in preoperative compared with healthy control subjects and increased after the surgery. The number of methanogens in the mucosa was decreased in preoperative patients but returned to normal levels postoperatively. In conclusion, although there was no difference in the structure of the predominant bacteria between refractory constipated patients and healthy control subjects, the number of probiotics ( Bifidobacteria and Lactobacilli) was significantly lower in refractory constipated patients. However, subtotal colectomy can significantly normalize the number of intestinal flora.
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Affiliation(s)
- Xiaobo Feng
- Department of General Surgery, JinLing Hospital, Medical School of Nanjing University, Nanjing, China; and the
| | - Yong Su
- Laboratory of Gastrointestinal Microbiology, Nanjing Agricultural University, Nanjing, China
| | - Jun Jiang
- Department of General Surgery, JinLing Hospital, Medical School of Nanjing University, Nanjing, China; and the
| | - Ning Li
- Department of General Surgery, JinLing Hospital, Medical School of Nanjing University, Nanjing, China; and the
| | - Weiwei Ding
- Department of General Surgery, JinLing Hospital, Medical School of Nanjing University, Nanjing, China; and the
| | - Zhiming Wang
- Department of General Surgery, JinLing Hospital, Medical School of Nanjing University, Nanjing, China; and the
| | - Xionghui Hu
- Department of General Surgery, JinLing Hospital, Medical School of Nanjing University, Nanjing, China; and the
| | - Weiyun Zhu
- Laboratory of Gastrointestinal Microbiology, Nanjing Agricultural University, Nanjing, China
| | - Jieshou Li
- Department of General Surgery, JinLing Hospital, Medical School of Nanjing University, Nanjing, China; and the
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50
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Lin EC, Massey BT. The Presence of Methanogenic Bacteria, Identified During Clinical Breath Testing, Is Not Associated with a Higher Body Mass Index in a U.S. Midwestern Population. Bariatr Surg Pract Patient Care 2014. [DOI: 10.1089/bari.2014.0028] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Emery C. Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Benson T. Massey
- Division of Gastroenterology and Hepatology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin
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