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Jain S. Does Schistosoma mansoni trigger colorectal cancer? Mol Biochem Parasitol 2025; 262:111672. [PMID: 39894059 DOI: 10.1016/j.molbiopara.2025.111672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Revised: 01/13/2025] [Accepted: 01/23/2025] [Indexed: 02/04/2025]
Abstract
In this work the relationship between Schistosoma mansoni (Sm) and the induction and progression of colorectal cancer (CRC) is examined. Various clinical studies reviewed here yield inconsistent results, with some reporting no association between Sm infection and CRC and others suggesting a probable to strong association. Here we propose a number of plausible mechanisms whereby Sm infection might contribute to CRC induction and/or progression. These factors are (1) chronic inflammation, (2) exposure to parasite linked antigens and genotoxic products, especially soluble egg antigens (SEAs) and (3) alteration of the intestinal microbiota. These factors probably predispose humans towards CRC and can help in CRC progression however only widespread epidemiological, clinical and pathological studies can firmly establish their role or a complete lack of it.
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Affiliation(s)
- Sidhant Jain
- Institute for Globally Distributed Open Research and Education (IGDORE), India.
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2
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Anthony DC, Probert F, Gorlova A, Hebert J, Radford-Smith D, Nefedova Z, Umriukhin A, Nedorubov A, Cespuglio R, Shulgin B, Lyundup A, Lesch KP, Strekalova T. Impact of Serotonin Transporter Absence on Brain Insulin Receptor Expression, Plasma Metabolome Changes, and ADHD-like Behavior in Mice fed a Western Diet. Biomolecules 2024; 14:884. [PMID: 39199273 PMCID: PMC11351952 DOI: 10.3390/biom14080884] [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: 06/04/2024] [Revised: 07/02/2024] [Accepted: 07/15/2024] [Indexed: 09/01/2024] Open
Abstract
The impaired function of the serotonin transporter (SERT) in humans has been linked to a higher risk of obesity and type 2 diabetes, especially as people age. Consuming a "Western diet" (WD), which is high in saturated fats, cholesterol, and sugars, can induce metabolic syndrome. Previous research indicated that mice carrying a targeted inactivation of the Sert gene (knockout, KO) and fed a WD display significant metabolic disturbances and behaviors reminiscent of ADHD. These abnormalities might be mediated via a dysfunction in insulin receptor (IR) signaling, which is also associated with adult ADHD. However, the impact of Sert deficiency on IR signaling and systemic metabolic changes has not been thoroughly explored. In this study, we conducted a detailed analysis of locomotor behavior in wild-type (WT) and KO mice fed a WD or control diet. We investigated changes in the blood metabolome and examined, via PCR, the expression of insulin receptor A and B isoforms and key regulators of their function in the brain. Twelve-month-old KO mice and their WT littermates were fed a WD for three weeks. Nuclear magnetic resonance spectroscopy analysis of plasma samples showed that KO mice on a WD had higher levels of lipids and lipoproteins and lower levels of glucose, lactate, alanine, valine, and isoleucine compared to other groups. SERT-KO mice on the control diet exhibited increased brain levels of both IR A and B isoforms, accompanied by a modest increase in the negative regulator ENPP. The KO mice also displayed anxiety-like behavior and reduced exploratory activity in an open field test. However, when the KO animals were fed a WD, the aberrant expression levels of IR isoforms in the KO mice and locomotor behavior were ameliorated indicating a complex interaction between genetic and dietary factors that might contribute to ADHD-like symptoms. Overall, our findings suggest that the lack of Sert leads to a unique metabolic phenotype in aged mice, characterized by dysregulated IR-related pathways. These changes are exacerbated by WD in the blood metabolome and are associated with behavioral abnormalities.
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Affiliation(s)
- Daniel C. Anthony
- Department of Pharmacology, Oxford University, Oxford OX1 3QT, UK; (D.C.A.); (F.P.); (J.H.); (D.R.-S.)
| | - Fay Probert
- Department of Pharmacology, Oxford University, Oxford OX1 3QT, UK; (D.C.A.); (F.P.); (J.H.); (D.R.-S.)
- Department of Chemistry, Oxford University, Oxford OX1 2JD, UK
| | - Anna Gorlova
- Research and Education Resource Center, Peoples Friendship University of Russia (RUDN University), 117198 Moscow, Russia; (A.G.); (R.C.); (A.L.)
| | - Jenna Hebert
- Department of Pharmacology, Oxford University, Oxford OX1 3QT, UK; (D.C.A.); (F.P.); (J.H.); (D.R.-S.)
| | - Daniel Radford-Smith
- Department of Pharmacology, Oxford University, Oxford OX1 3QT, UK; (D.C.A.); (F.P.); (J.H.); (D.R.-S.)
| | - Zlata Nefedova
- Department of Normal Physiology, Sechenov First Moscow State Medical University, 119991 Moscow, Russia; (Z.N.); (A.U.); (A.N.)
| | - Aleksei Umriukhin
- Department of Normal Physiology, Sechenov First Moscow State Medical University, 119991 Moscow, Russia; (Z.N.); (A.U.); (A.N.)
| | - Andrey Nedorubov
- Department of Normal Physiology, Sechenov First Moscow State Medical University, 119991 Moscow, Russia; (Z.N.); (A.U.); (A.N.)
| | - Raymond Cespuglio
- Research and Education Resource Center, Peoples Friendship University of Russia (RUDN University), 117198 Moscow, Russia; (A.G.); (R.C.); (A.L.)
| | - Boris Shulgin
- Laboratory of Engineering Profile Physical and Chemical Methods of Analysis, Korkyt Ata Kyzylorda University, Kyzylorda 120014, Kazakhstan;
| | - Aleksey Lyundup
- Research and Education Resource Center, Peoples Friendship University of Russia (RUDN University), 117198 Moscow, Russia; (A.G.); (R.C.); (A.L.)
- Endocrinology Research Centre, Dmitry Ulyanov Str. 19, 117036 Moscow, Russia
| | - Klaus Peter Lesch
- Division of Molecular Psychiatry, Center of Mental Health, University Hospital Würzburg, 97080 Würzburg, Germany;
- Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Würzburg, 97080 Würzburg, Germany
| | - Tatyana Strekalova
- Department of Pharmacology, Oxford University, Oxford OX1 3QT, UK; (D.C.A.); (F.P.); (J.H.); (D.R.-S.)
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Chienwichai P, Tipthara P, Tarning J, Limpanont Y, Chusongsang P, Chusongsang Y, Kiangkoo N, Adisakwattana P, Reamtong O. Identification of trans-genus biomarkers for early diagnosis of intestinal schistosomiasis and progression of gut pathology in a mouse model using metabolomics. PLoS Negl Trop Dis 2024; 18:e0011966. [PMID: 38381759 PMCID: PMC10880994 DOI: 10.1371/journal.pntd.0011966] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Accepted: 02/05/2024] [Indexed: 02/23/2024] Open
Abstract
Schistosomiasis is one of the most devastating human diseases worldwide. The disease is caused by six species of Schistosoma blood fluke; five of which cause intestinal granulomatous inflammation and bleeding. The current diagnostic method is inaccurate and delayed, hence, biomarker identification using metabolomics has been applied. However, previous studies only investigated infection caused by one Schistosoma spp., leaving a gap in the use of biomarkers for other species. No study focused on understanding the progression of intestinal disease. Therefore, we aimed to identify early gut biomarkers of infection with three Schistosoma spp. and progression of intestinal pathology. We infected 3 groups of mice, 3 mice each, with Schistosoma mansoni, Schistosoma japonicum or Schistosoma mekongi and collected their feces before and 1, 2, 4 and 8 weeks after infection. Metabolites in feces were extracted and identified using mass spectrometer-based metabolomics. Metabolites were annotated and analyzed with XCMS bioinformatics tool and Metaboanalyst platform. From >36,000 features in all conditions, multivariate analysis found a distinct pattern at each time point for all species. Pathway analysis reported alteration of several lipid metabolism pathways as infection progressed. Disturbance of the glycosaminoglycan degradation pathway was found with the presence of parasite eggs, indicating involvement of this pathway in disease progression. Biomarkers were discovered using a combination of variable importance for projection score cut-off and receiver operating characteristic curve analysis. Five molecules met our criteria and were present in all three species: 25-hydroxyvitamin D2, 1α-hydroxy-2β-(3-hydroxypropoxy) vitamin D3, Ganoderic acid Md, unidentified feature with m/z 455.3483, and unidentified feature with m/z 456.3516. These molecules were proposed as trans-genus biomarkers of early schistosomiasis. Our findings provide evidence for disease progression in intestinal schistosomiasis and potential biomarkers, which could be beneficial for early detection of this disease.
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Affiliation(s)
- Peerut Chienwichai
- Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Phornpimon Tipthara
- Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Joel Tarning
- Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
- Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom
| | - Yanin Limpanont
- Department of Social and Environmental Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Phiraphol Chusongsang
- Department of Social and Environmental Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Yupa Chusongsang
- Department of Social and Environmental Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Nuttapohn Kiangkoo
- Department of Social and Environmental Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Poom Adisakwattana
- Department of Helminthology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Onrapak Reamtong
- Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
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Jain S, Rana M. From the discovery of helminths to the discovery of their carcinogenic potential. Parasitol Res 2023; 123:47. [PMID: 38095695 DOI: 10.1007/s00436-023-08022-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2023] [Accepted: 11/20/2023] [Indexed: 12/18/2023]
Abstract
Cancer involves a major aberration in the normal behaviour of cells, making them divide continuously, which interferes with the normal physiology of the body. The link between helminths and their cancer-inducing potential has been proposed in the last century. The exact pathway is still not clear but chronic inflammation in response to the deposited eggs, immune response against soluble egg antigens, and co-infection with a third party (a bacteria, a virus, or infection leading to a change in microbiome) seems to be the reasons for cancer induction. This review looks into the historical outlook on helminths along with their epidemiology, morphology, and life cycle. It then focuses on providing correlations between helminth infection and molecular mechanism of carcinogenesis by elaborating upon epidemiological, clinical, and surgical studies. While the cancer-inducing potential has been convincingly established only for a few helminths and studies point out towards possible cancer-inducing ability of the rest of the helminths elucidated in this work, however, more insights into the immunobiology of helminths as well as infected patients are required to conclusively comment upon this ability of the latter.
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Affiliation(s)
- Sidhant Jain
- Institute for Globally Distributed Open Research and Education (IGDORE), Rewari, Haryana, India.
| | - Meenakshi Rana
- Dyal Singh College, University of Delhi, Lodhi Road, Pragati Vihaar, New Delhi, India
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Midzi H, Vengesai A, Muleya V, Kasambala M, Mduluza-Jokonya TL, Chipako I, Siamayuwa CE, Mutapi F, Naicker T, Mduluza T. Metabolomics for biomarker discovery in schistosomiasis: A systematic scoping review. FRONTIERS IN TROPICAL DISEASES 2023. [DOI: 10.3389/fitd.2023.1108317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
BackgroundMetabolomic based approaches are essential tools in the discovery of unique biomarkers for infectious diseases via high-throughput global assessment of metabolites and metabolite pathway dysregulation. This in-turn allows the development of diagnostic tools and provision of therapeutics. In this review, we aimed to give an overview of metabolite biomarkers and metabolic pathway alterations during Schistosoma haematobium and Schistosoma mansoni infections.MethodsWe conducted the review by systematically searching electronic databases and grey literature to identify relevant metabolomics studies on schistosomiasis. Arksey and O’Malley methodology for conducting systematic scoping reviews was applied. A narrative summary of results was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for scoping review guidelines.ResultsTwelve articles included in the review identified 127 metabolites, whose concentrations were considerably altered during S. mansoni and S. haematobium infections. The metabolites were assigned to metabolic pathways involved in energy (34.6%), gut microbial (11.0%), amino acid (25.2%), nucleic acids (6.3%), immune proteins (8.7%) hormones (2.4%) and structural proteins/lipids (11.8%). Energy related metabolic pathways were the most affected during schistosome infections with metabolites such as succinate, citrate, aconitate and fumarate of the tricarbocylic acid cycle being significantly altered in organ, serum and plasma samples. Amino acid metabolism was also impacted during schistosome infections as phenylacetylglycine, alanine, taurine, 2-oxoisocaproate and 2-oxoisovalerate emerged as potent biomarkers. Elevated structural proteins such as actin, collagen and keratin concentrations were identified as biomarkers of liver fibrosis, a common pathological feature in chronic schistosomiasis infections. Hippurate was a major metabolite biomarker in the gut microbial related pathway.ConclusionsThe analysis of the literature revealed that energy related metabolic pathways are considerably altered during S. mansoni and S. haematobium infections. Therefore, their metabolites may provide biomarkers for diagnosis and prognosis in addition to providing therapeutics for parasitic infections. This scoping review has identified a need to replicate more schistosomiasis metabolomic studies in humans to complement animal-model based studies.
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Cortés A, Martin J, Rosa BA, Stark KA, Clare S, McCarthy C, Harcourt K, Brandt C, Tolley C, Lawley TD, Mitreva M, Berriman M, Rinaldi G, Cantacessi C. The gut microbial metabolic capacity of microbiome-humanized vs. wild type rodents reveals a likely dual role of intestinal bacteria in hepato-intestinal schistosomiasis. PLoS Negl Trop Dis 2022; 16:e0010878. [PMID: 36279280 PMCID: PMC9633004 DOI: 10.1371/journal.pntd.0010878] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 11/03/2022] [Accepted: 10/09/2022] [Indexed: 11/06/2022] Open
Abstract
Increasing evidence shows that the host gut microbiota might be involved in the immunological cascade that culminates with the formation of tissue granulomas underlying the pathophysiology of hepato-intestinal schistosomiasis. In this study, we investigated the impact of Schistosoma mansoni infection on the gut microbial composition and functional potential of both wild type and microbiome-humanized mice. In spite of substantial differences in microbiome composition at baseline, selected pathways were consistently affected by parasite infection. The gut microbiomes of infected mice of both lines displayed, amongst other features, enhanced capacity for tryptophan and butyrate production, which might be linked to the activation of mechanisms aimed to prevent excessive injuries caused by migrating parasite eggs. Complementing data from previous studies, our findings suggest that the host gut microbiome might play a dual role in the pathophysiology of schistosomiasis, where intestinal bacteria may contribute to egg-associated pathology while, in turn, protect the host from uncontrolled tissue damage.
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Affiliation(s)
- Alba Cortés
- Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom
- Departament de Farmàcia, Tecnologia Farmacèutica i Parasitologia, Facultat de Farmàcia, Universitat de València, Burjassot, València, Spain
| | - John Martin
- Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Bruce A. Rosa
- Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Klara A. Stark
- Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom
| | - Simon Clare
- Department of Medicine, University of Cambridge, Cambridge, United Kingdom
- Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom
| | - Catherine McCarthy
- Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom
| | - Katherine Harcourt
- Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom
| | - Cordelia Brandt
- Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom
| | - Charlotte Tolley
- Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom
- Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, United Kingdom
| | - Trevor D. Lawley
- Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom
| | - Makedonka Mitreva
- Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Matthew Berriman
- Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom
| | - Gabriel Rinaldi
- Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom
| | - Cinzia Cantacessi
- Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom
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Yeshi K, Ruscher R, Loukas A, Wangchuk P. Immunomodulatory and biological properties of helminth-derived small molecules: Potential applications in diagnostics and therapeutics. FRONTIERS IN PARASITOLOGY 2022; 1:984152. [PMID: 39816468 PMCID: PMC11731824 DOI: 10.3389/fpara.2022.984152] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Accepted: 08/23/2022] [Indexed: 01/18/2025]
Abstract
Parasitic helminths secrete and excrete a vast array of molecules known to help skew or suppress the host's immune response, thereby establishing a niche for sustained parasite maintenance. Indeed, the immunomodulatory potency of helminths is attributed mainly to excretory/secretory products (ESPs). The ESPs of helminths and the identified small molecules (SM) are reported to have diverse biological and pharmacological properties. The available literature reports only limited metabolites, and the identity of many metabolites remains unknown due to limitations in the identification protocols and helminth-specific compound libraries. Many metabolites are known to be involved in host-parasite interactions and pathogenicity. For example, fatty acids (e.g., stearic acid) detected in the infective stages of helminths are known to have a role in host interaction through facilitating successful penetration and migration inside the host. Moreover, excreted/secreted SM detected in helminth species are found to possess various biological properties, including anti-inflammatory activities, suggesting their potential in developing immunomodulatory drugs. For example, helminths-derived somatic tissue extracts and whole crude ESPs showed anti-inflammatory properties by inhibiting the secretion of proinflammatory cytokines from human peripheral blood mononuclear cells and suppressing the pathology in chemically-induced experimental mice model of colitis. Unlike bigger molecules like proteins, SM are ideal candidates for drug development since they are small structures, malleable, and lack immunogenicity. Future studies should strive toward identifying unknown SM and isolating the under-explored niche of helminth metabolites using the latest metabolomics technologies and associated software, which hold potential keys for finding new diagnostics and novel therapeutics.
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Affiliation(s)
- Karma Yeshi
- Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine (AITHM), James Cook University, Cairns, QLD, Australia
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Chienwichai P, Nogrado K, Tipthara P, Tarning J, Limpanont Y, Chusongsang P, Chusongsang Y, Tanasarnprasert K, Adisakwattana P, Reamtong O. Untargeted serum metabolomic profiling for early detection of Schistosoma mekongi infection in mouse model. Front Cell Infect Microbiol 2022; 12:910177. [PMID: 36061860 PMCID: PMC9433908 DOI: 10.3389/fcimb.2022.910177] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 07/29/2022] [Indexed: 11/13/2022] Open
Abstract
Mekong schistosomiasis is a parasitic disease caused by blood flukes in the Lao People’s Democratic Republic and in Cambodia. The standard method for diagnosis of schistosomiasis is detection of parasite eggs from patient samples. However, this method is not sufficient to detect asymptomatic patients, low egg numbers, or early infection. Therefore, diagnostic methods with higher sensitivity at the early stage of the disease are needed to fill this gap. The aim of this study was to identify potential biomarkers of early schistosomiasis using an untargeted metabolomics approach. Serum of uninfected and S. mekongi-infected mice was collected at 2, 4, and 8 weeks post-infection. Samples were extracted for metabolites and analyzed with a liquid chromatography-tandem mass spectrometer. Metabolites were annotated with the MS-DIAL platform and analyzed with Metaboanalyst bioinformatic tools. Multivariate analysis distinguished between metabolites from the different experimental conditions. Biomarker screening was performed using three methods: correlation coefficient analysis; feature important detection with a random forest algorithm; and receiver operating characteristic (ROC) curve analysis. Three compounds were identified as potential biomarkers at the early stage of the disease: heptadecanoyl ethanolamide; picrotin; and theophylline. The levels of these three compounds changed significantly during early-stage infection, and therefore these molecules may be promising schistosomiasis markers. These findings may help to improve early diagnosis of schistosomiasis, thus reducing the burden on patients and limiting spread of the disease in endemic areas.
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Affiliation(s)
- Peerut Chienwichai
- Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Kathyleen Nogrado
- Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Phornpimon Tipthara
- Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Joel Tarning
- Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
- Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom
| | - Yanin Limpanont
- Department of Social and Environmental Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Phiraphol Chusongsang
- Department of Social and Environmental Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Yupa Chusongsang
- Department of Social and Environmental Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Kanthi Tanasarnprasert
- Department of Social and Environmental Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Poom Adisakwattana
- Department of Helminthology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Onrapak Reamtong
- Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
- *Correspondence: Onrapak Reamtong,
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Rodrigues ML, da Luz TPSR, Pereira CLD, Batista AD, Domingues ALC, Silva RO, Lopes EP. Assessment of periportal fibrosis in Schistosomiasis mansoni patients by proton nuclear magnetic resonance-based metabonomics models. World J Hepatol 2022; 14:719-728. [PMID: 35646266 PMCID: PMC9099102 DOI: 10.4254/wjh.v14.i4.719] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Revised: 07/20/2021] [Accepted: 03/25/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The evaluation of periportal fibrosis (PPF) is essential for a prognostic assessment of patients with Schistosomiasis mansoni. The WHO Niamey Protocol defines patterns of fibrosis from abdominal ultrasonography, 1H-nuclear magnetic resonance (NMR)-based metabonomics has been employed to assess liver fibrosis in some diseases. AIM To build 1H-NMR-based metabonomics models (MM) to discriminate mild from significant periportal PPF and identify differences in the metabolite profiles. METHODS A prospective cross-sectional study was performed on schistosomiasis patients at a University Hospital in Northeastern Brazil. We evaluated 41 serum samples from 10 patients with mild PPF (C Niamey pattern) and 31 patients with significant PPF (D/E/F Niamey patterns). MM were built using partial least squares-discriminant analysis (PLS-DA) and orthogonal projections to latent structures discriminant analysis (OPLS-DA) formalisms. RESULTS PLS-DA and OPLS-DA resulted in discrimination between mild and significant PPF groups with R2 and Q2 values of 0.80 and 0.38 and 0.72 and 0.42 for each model, respectively. The OPLS-DA model presented accuracy, sensitivity, and specificity values of 92.7%, 90.3%, and 100% to discriminate significant PPF. The metabolites identified as responsible by discrimination were: N-acetylglucosamines, alanine, glycolaldehyde, carbohydrates, and valine. CONCLUSION MMs discriminated mild from significant PPF patterns in patients with Schistosomiasis mansoni through identification of differences in serum metabolites profiles.
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Affiliation(s)
- Milena Lima Rodrigues
- Programa de Pós-Graduação em Medicina Tropical, Centro de Ciências Médicas, Universidade Federal de Pernambuco, Recife 50670-901, Pernambuco, Brazil
| | | | - Caroline Louise Diniz Pereira
- Programa de Pós-Graduação em Medicina Tropical, Centro de Ciências Médicas, Universidade Federal de Pernambuco, Recife 50670-901, Pernambuco, Brazil
| | - Andrea Dória Batista
- Hospital das Clínicas, Departamento de Medicina Clínica, Universidade Federal de Pernambuco, Recife 50670-901, Pernambuco, Brazil
| | - Ana Lúcia Coutinho Domingues
- Programa de Pós-Graduação em Medicina Tropical, Centro de Ciências Médicas, Universidade Federal de Pernambuco, Recife 50670-901, Pernambuco, Brazil
- Hospital das Clínicas, Departamento de Medicina Clínica, Universidade Federal de Pernambuco, Recife 50670-901, Pernambuco, Brazil
| | - Ricardo Oliveira Silva
- Programa de Pós-Graduação em Química, Centro de Ciências Exatas e da Natureza, Universidade Federal de Pernambuco, Recife 50670-740, Pernambuco, Brazil
| | - Edmundo Pessoa Lopes
- Programa de Pós-Graduação em Medicina Tropical, Centro de Ciências Médicas, Universidade Federal de Pernambuco, Recife 50670-901, Pernambuco, Brazil
- Hospital das Clínicas, Departamento de Medicina Clínica, Universidade Federal de Pernambuco, Recife 50670-901, Pernambuco, Brazil.
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Ndolo SM, Zachariah M, Molefi L, Phaladze N, Sichilongo KF. Mass spectrometry based metabolomics for small molecule metabolites mining and confirmation as potential biomarkers for schistosomiasis - case of the Okavango Delta communities in Botswana. Expert Rev Proteomics 2021; 19:61-71. [PMID: 34846232 DOI: 10.1080/14789450.2021.2012454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
INTRODUCTION Metabolomics for identifying schistosomiasis biomarkers in noninvasive samples at various infection stages is being actively explored. The literature on the traditional detection of schistosomiasis in human specimens is well documented. However, state-of-the-art technologies based on mass spectrometry have simplified the use of biomarkers for diagnostics. This review examines methods currently in use for the metabolomics of small molecules using separation science and mass spectrometry. AREA COVERED This article highlights the evolution of traditional diagnostic methods for schistosomiasis based on inter alia microscopy, immunology, and polymerase chain reaction. An exhaustive literature search of metabolite mining, focusing on separation science and mass spectrometry, is presented. A comparative analysis of mass spectrometry methods was undertaken, including a projection for the future. EXPERT COMMENTARY Mass spectrometry metabolomics for schistosomiasis will lead to biomarker discovery for noninvasive human samples. These biomarkers, together with those from other neglected tropical diseases, such as malaria and sleeping sickness, could be incorporated as arrays on a single biosensor chip and inserted into smartphones, in order to improve surveillance, monitoring, and management.
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Affiliation(s)
- Sedireng M Ndolo
- College of Open Schooling, Botswana Open University, Gaborone Regional Campus, Gaborone, Botswana
| | - Matshediso Zachariah
- School of Allied Health Professions, Faculty of Health Sciences, University of Botswana, Gaborone, Botswana
| | - Lebotse Molefi
- School of Allied Health Professions, Faculty of Health Sciences, University of Botswana, Gaborone, Botswana
| | - Nthabiseng Phaladze
- School of Nursing, Faculty of Health Sciences, University of Botswana, Gaborone, Botswana
| | - Kwenga F Sichilongo
- Chemistry Department, Faculty of Science, University of Botswana, Gaborone, Botswana
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11
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Haonon O, Liu Z, Dangtakot R, Intuyod K, Pinlaor P, Puapairoj A, Cha'on U, Sengthong C, Pongking T, Onsurathum S, Yingklang M, Phetcharaburanin J, Li JV, Pinlaor S. Opisthorchis viverrini Infection Induces Metabolic and Fecal Microbial Disturbances in Association with Liver and Kidney Pathologies in Hamsters. J Proteome Res 2021; 20:3940-3951. [PMID: 34270897 DOI: 10.1021/acs.jproteome.1c00246] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Opisthorchis viverrini (Ov) infection causes hepatobiliary diseases and is a major risk factor for cholangiocarcinoma. While several omics approaches have been employed to understand the pathogenesis of opisthorchiasis, effects of Ov infection on the host systemic metabolism and fecal microbiota have not been fully explored. Here, we used a 1H NMR spectroscopy-based metabolic phenotyping approach to investigate Ov infection-induced metabolic disturbances at both the acute (1 month postinfection, 1 mpi) and chronic (4 mpi) stages in hamsters. A total of 22, 3, and 4 metabolites were found to be significantly different in the liver, serum, and urine, respectively, between Ov+ and Ov- groups. Elevated levels of hepatic amino acids and tricarboxylic acid (TCA)-cycle intermediates (fumarate and malate) were co-observed with liver injury in acute infection, whereas fibrosis-associated metabolites (e.g., glycine and glutamate) increased at the chronic infection stage. Lower levels of lipid signals ((CH2)n and CH2CH2CO) and higher levels of lysine and scyllo-inositol were observed in serum from Ov+ hamsters at 1 mpi compared to Ov- controls. Urinary levels of phenylacetylglycine (a host-bacterial cometabolite) and tauro-β-muricholic acid were higher in the Ov+ group, which coexisted with hepatic and mild kidney fibrosis. Furthermore, Ov+ animals showed higher relative abundances of fecal Methanobrevibacter (Archaea), Akkermansia, and Burkholderia-Paraburkholderia compared to the noninfected controls. In conclusion, along with liver and kidney pathologies, O. viverrini infection resulted in hepatic and mild renal pathologies, disturbed hepatic amino acid metabolism and the TCA cycle, and induced changes in the fecal microbial composition and urinary host-microbial cometabolism. This study provides the initial step toward an understanding of local and systemic metabolic responses of the host to O. viverrini infection.
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Affiliation(s)
- Ornuma Haonon
- Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.,Chronic Kidney Disease Prevention in the Northeast of Thailand (CKDNET), Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Zhigang Liu
- Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London SW7 2AZ, U.K
| | - Rungtiwa Dangtakot
- Faculty of Medical Technology, Nakhonratchasima College, Nakhon Ratchasima 30000, Thailand
| | - Kitti Intuyod
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Porntip Pinlaor
- Chronic Kidney Disease Prevention in the Northeast of Thailand (CKDNET), Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.,Centre for Research and Development in Medical Diagnostic Laboratory, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Anucha Puapairoj
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Ubon Cha'on
- Chronic Kidney Disease Prevention in the Northeast of Thailand (CKDNET), Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.,Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Chatchawan Sengthong
- Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.,Chronic Kidney Disease Prevention in the Northeast of Thailand (CKDNET), Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Thatsanapong Pongking
- Chronic Kidney Disease Prevention in the Northeast of Thailand (CKDNET), Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.,Biomedical Science Program, Graduate School, Khon Kaen University, Khon Kaen 40002, Thailand.,Centre for Research and Development in Medical Diagnostic Laboratory, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Sudarat Onsurathum
- Department of Microbiology and Parasitology, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand
| | - Manachai Yingklang
- Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.,Chronic Kidney Disease Prevention in the Northeast of Thailand (CKDNET), Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Jutarop Phetcharaburanin
- Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Jia V Li
- Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London SW7 2AZ, U.K
| | - Somchai Pinlaor
- Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.,Chronic Kidney Disease Prevention in the Northeast of Thailand (CKDNET), Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
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12
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Rodríguez-Hernández P, Cardador MJ, Arce L, Rodríguez-Estévez V. Analytical Tools for Disease Diagnosis in Animals via Fecal Volatilome. Crit Rev Anal Chem 2020; 52:917-932. [PMID: 33180561 DOI: 10.1080/10408347.2020.1843130] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Volatilome analysis is growing in attention for the diagnosis of diseases in animals and humans. In particular, volatilome analysis in fecal samples is starting to be proposed as a fast, easy and noninvasive method for disease diagnosis. Volatilome comprises volatile organic compounds (VOCs), which are produced during both physiological and patho-physiological processes. Thus, VOCs from a pathological condition often differ from those of a healthy state and therefore the VOCs profile can be used in the detection of some diseases. Due to their strengths and advantages, feces are currently being used to obtain information related to health status in animals. However, they are complex samples, that can present problems for some analytical techniques and require special consideration in their use and preparation before analysis. This situation demands an effort to clarify which analytic options are currently being used in the research context to analyze the possibilities these offer, with the final objectives of contributing to develop a standardized methodology and to exploit feces potential as a diagnostic matrix. The current work reviews the studies focused on the diagnosis of animal diseases through fecal volatilome in order to evaluate the analytical methods used and their advantages and limitations. The alternatives found in the literature for sampling, storage, sample pretreatment, measurement and data treatment have been summarized, considering all the steps involved in the analytical process.
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Affiliation(s)
| | - M J Cardador
- Department of Analytical Chemistry, Institute of Fine Chemistry and Nanochemistry, University of Córdoba, Córdoba, Spain
| | - L Arce
- Department of Analytical Chemistry, Institute of Fine Chemistry and Nanochemistry, University of Córdoba, Córdoba, Spain
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13
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Loyo RM, Zarate E, Barbosa CS, Simoes-Barbosa A. Gas chromatography-mass spectrometry (GC/MS) reveals urine metabolites associated to light and heavy infections by Schistosoma mansoni in mice. Parasitol Int 2020; 80:102239. [PMID: 33157242 DOI: 10.1016/j.parint.2020.102239] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 10/07/2020] [Accepted: 10/10/2020] [Indexed: 11/17/2022]
Abstract
High-throughput profiling of metabolites has been used to identify metabolic changes in murine models as a response to the infection by the parasitic trematode Schistosoma. These investigations have contributed to our understanding on the pathogenesis of this tropical neglected disease, with a potential of helping diagnosis. Here, our study aimed to investigate the application of gas chromatography-mass spectrometry (GC/MS) on the profiling of urine metabolites from mice carrying infections by Schistosoma mansoni. Two larval infection doses created distinctive infection intensities in mice, whereby the heavily infected animals were found to release 25 times more eggs in faeces than lightly infected animals. Over 200 urine metabolites were identified from these animals by GC/MS, following two complementary derivatisation methods. A list of 14 individual metabolites with altered relative abundances between groups were identified. Most of the altered metabolites showed a trend of increased abundances in response to infection intensity, indicating host-specific metabolic alterations as a result of the disease. Hippurate, a metabolite which concentration is intimately modulated by the gut microbiota, was found to be highly correlated to infection intensity. Our study showed that urine metabolic profiling by GC/MS can distinguish non-infected animals from those carrying light and heavy infections by S. mansoni, revealing metabolites associated to the infection and providing insights on the pathogenesis of schistosomiasis.
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Affiliation(s)
- Rodrigo Moraes Loyo
- Laboratory and reference service on Schistosomiasis, Aggeu Magalhães Institute, Oswaldo Cruz foundation (Fiocruz), Recife, PE, Brazil; School of Biological Sciences, University of Auckland, Auckland, New Zealand.
| | - Erica Zarate
- School of Biological Sciences, University of Auckland, Auckland, New Zealand.
| | - Constança Simões Barbosa
- Laboratory and reference service on Schistosomiasis, Aggeu Magalhães Institute, Oswaldo Cruz foundation (Fiocruz), Recife, PE, Brazil.
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14
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Twenty Years on: Metabolomics in Helminth Research. Trends Parasitol 2019; 35:282-288. [DOI: 10.1016/j.pt.2019.01.012] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2018] [Revised: 01/20/2019] [Accepted: 01/29/2019] [Indexed: 11/23/2022]
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15
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Costain AH, MacDonald AS, Smits HH. Schistosome Egg Migration: Mechanisms, Pathogenesis and Host Immune Responses. Front Immunol 2018; 9:3042. [PMID: 30619372 PMCID: PMC6306409 DOI: 10.3389/fimmu.2018.03042] [Citation(s) in RCA: 132] [Impact Index Per Article: 18.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2018] [Accepted: 12/10/2018] [Indexed: 12/22/2022] Open
Abstract
Many parasitic worms possess complex and intriguing life cycles, and schistosomes are no exception. To exit the human body and progress to their successive snail host, Schistosoma mansoni eggs must migrate from the mesenteric vessels, across the intestinal wall and into the feces. This process is complex and not always successful. A vast proportion of eggs fail to leave their definite host, instead becoming lodged within intestinal or hepatic tissue, where they can evoke potentially life-threatening pathology. Thus, to maximize the likelihood of successful egg passage whilst minimizing host pathology, intriguing egg exit strategies have evolved. Notably, schistosomes actively exert counter-inflammatory influences on the host immune system, discreetly compromise endothelial and epithelial barriers, and modulate granuloma formation around transiting eggs, which is instrumental to their migration. In this review, we discuss new developments in our understanding of schistosome egg migration, with an emphasis on S. mansoni and the intestine, and outline the host-parasite interactions that are thought to make this process possible. In addition, we explore the potential immune implications of egg penetration and discuss the long-term consequences for the host of unsuccessful egg transit, such as fibrosis, co-infection and cancer development.
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Affiliation(s)
- Alice H. Costain
- Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands
- Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester, United Kingdom
| | - Andrew S. MacDonald
- Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester, United Kingdom
| | - Hermelijn H. Smits
- Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands
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16
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Hough R, Archer D, Probert C. A comparison of sample preparation methods for extracting volatile organic compounds (VOCs) from equine faeces using HS-SPME. Metabolomics 2018; 14:19. [PMID: 29367839 PMCID: PMC5754382 DOI: 10.1007/s11306-017-1315-7] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Accepted: 12/22/2017] [Indexed: 11/15/2022]
Abstract
INTRODUCTION Disturbance to the hindgut microbiota can be detrimental to equine health. Metabolomics provides a robust approach to studying the functional aspect of hindgut microorganisms. Sample preparation is an important step towards achieving optimal results in the later stages of analysis. The preparation of samples is unique depending on the technique employed and the sample matrix to be analysed. Gas chromatography mass spectrometry (GCMS) is one of the most widely used platforms for the study of metabolomics and until now an optimised method has not been developed for equine faeces. OBJECTIVES To compare a sample preparation method for extracting volatile organic compounds (VOCs) from equine faeces. METHODS Volatile organic compounds were determined by headspace solid phase microextraction gas chromatography mass spectrometry (HS-SPME-GCMS). Factors investigated were the mass of equine faeces, type of SPME fibre coating, vial volume and storage conditions. RESULTS The resultant method was unique to those developed for other species. Aliquots of 1000 or 2000 mg in 10 ml or 20 ml SPME headspace were optimal. From those tested, the extraction of VOCs should ideally be performed using a divinylbenzene-carboxen-polydimethysiloxane (DVB-CAR-PDMS) SPME fibre. Storage of faeces for up to 12 months at - 80 °C shared a greater percentage of VOCs with a fresh sample than the equivalent stored at - 20 °C. CONCLUSIONS An optimised method for extracting VOCs from equine faeces using HS-SPME-GCMS has been developed and will act as a standard to enable comparisons between studies. This work has also highlighted storage conditions as an important factor to consider in experimental design for faecal metabolomics studies.
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Affiliation(s)
- Rachael Hough
- Department of Cellular and Molecular Physiology, University of Liverpool, Liverpool, UK.
| | - Debra Archer
- Department of Epidemiology and Population Health, University of Liverpool, Liverpool, UK
| | - Christopher Probert
- Department of Cellular and Molecular Physiology, University of Liverpool, Liverpool, UK
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17
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De Pascali SA, Gambacorta L, Oswald IP, Del Coco L, Solfrizzo M, Fanizzi FP. 1H NMR and MVA metabolomic profiles of urines from piglets fed with boluses contaminated with a mixture of five mycotoxins. Biochem Biophys Rep 2017; 11:9-18. [PMID: 28955762 PMCID: PMC5614695 DOI: 10.1016/j.bbrep.2017.05.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2016] [Revised: 03/28/2017] [Accepted: 05/24/2017] [Indexed: 01/03/2023] Open
Abstract
Metabolic profile of urine from piglets administered with single boluses contaminated with mycotoxin mixture (deoxynivalenol, aflatoxin B1, fumonisin B1, zearalenone, and ochratoxin A) were studied by 1H NMR spectroscopy and chemometrics (PCA, PLS-DA, and OPLS-DA). The mycotoxin levels were close to the established maximum and guidance levels for animal feed (2003/100/EC and 2006/576/EC). Urine samples were obtained from four groups of four piglets before (control, C) or within 24 h (treated, T) after receiving a contaminated boluses with increasing doses of mycotoxins (boluses 1-4). For the two highest dose groups, the urines were collected also after one week of wash out (W). For the two lowest doses groups no significant differences between the C and T samples were observed. By contrast, for the two highest doses groups the T urines separated from the controls for a higher relative content of creatinine, p-cresol glucuronide and phenyl acetyl glycine and lower concentration of betaine and TMAO. Interestingly, a similar profile was found for both W and T urines suggesting, at least for the highest doses used, serious alteration after a single bolus of mycotoxin mixture.
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Affiliation(s)
- Sandra A. De Pascali
- University of Salento, Di.S.Te.B.A., Campus Ecotekne, via Provle Lecce-Monteroni, 73100, Lecce, Italy
| | - Lucia Gambacorta
- Institute of Sciences of Food Production (ISPA), National Research Council of Italy (CNR), Via Amendola 122/O, 70126 Bari, Italy
| | - Isabelle P. Oswald
- UMR 1331 Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, 180 Chemin de Tournefeuille, F-31027 Toulouse, Cedex, France
| | - Laura Del Coco
- University of Salento, Di.S.Te.B.A., Campus Ecotekne, via Provle Lecce-Monteroni, 73100, Lecce, Italy
| | - Michele Solfrizzo
- Institute of Sciences of Food Production (ISPA), National Research Council of Italy (CNR), Via Amendola 122/O, 70126 Bari, Italy
| | - Francesco Paolo Fanizzi
- University of Salento, Di.S.Te.B.A., Campus Ecotekne, via Provle Lecce-Monteroni, 73100, Lecce, Italy
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18
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Gouveia LR, Santos JC, Silva RD, Batista AD, Domingues ALC, Lopes EPDA, Silva RO. Diagnosis of coinfection by schistosomiasis and viral hepatitis B or C using 1H NMR-based metabonomics. PLoS One 2017; 12:e0182196. [PMID: 28763497 PMCID: PMC5538707 DOI: 10.1371/journal.pone.0182196] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Accepted: 07/13/2017] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Diagnosis of liver involvement due to schistosomiasis in asymptomatic patients from endemic areas previously diagnosed with chronic hepatitis B (HBV) or C (HCV) and periportal fibrosis is challenging. H-1 Nuclear Magnetic Resonance (NMR)-based metabonomics strategy is a powerful tool for providing a profile of endogenous metabolites of low molecular weight in biofluids in a non-invasive way. The aim of this study was to diagnose periportal fibrosis due to schistosomiasis mansoni in patients with chronic HBV or HCV infection through NMR-based metabonomics models. METHODOLOGY/PRINCIPAL FINDINGS The study included 40 patients divided into two groups: (i) 18 coinfected patients with schistosomiasis mansoni and HBV or HCV; and (ii) 22 HBV or HCV monoinfected patients. The serum samples were analyzed through H-1 NMR spectroscopy and the models were based on Principal Component Analysis (PCA) and Partial Least Squares-Discriminant Analysis (PLS-DA). Ultrasonography examination was used to ascertain the diagnosis of periportal fibrosis. Exploratory analysis showed a clear separation between coinfected and monoinfected samples. The supervised model built from PLS-DA showed accuracy, R2 and Q2 values equal to 100%, 98.1% and 97.5%, respectively. According to the variable importance in the projection plot, lactate serum levels were higher in the coinfected group, while the signals attributed to HDL serum cholesterol were more intense in the monoinfected group. CONCLUSIONS/SIGNIFICANCE The metabonomics models constructed in this study are promising as an alternative tool for diagnosis of periportal fibrosis by schistosomiasis in patients with chronic HBV or HCV infection from endemic areas for Schistosoma mansoni.
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Affiliation(s)
- Liana Ribeiro Gouveia
- Postgraduate Program in Chemistry, Fundamental Chemistry Department, Center for Exact and Natural Sciences, Universidade Federal de Pernambuco (UFPE), Recife, Pernambuco, Brazil
| | - Joelma Carvalho Santos
- Postgraduate Program in Tropical Medicine, Center for Health Sciences, Universidade Federal de Pernambuco (UFPE), Recife, Pernambuco, Brazil
| | - Ronaldo Dionísio Silva
- Postgraduate Program in Chemistry, Fundamental Chemistry Department, Center for Exact and Natural Sciences, Universidade Federal de Pernambuco (UFPE), Recife, Pernambuco, Brazil
| | - Andrea Dória Batista
- Postgraduate Program in Tropical Medicine, Center for Health Sciences, Universidade Federal de Pernambuco (UFPE), Recife, Pernambuco, Brazil
- Department of Internal Medicine, Hospital das Clínicas, Universidade Federal de Pernambuco (UFPE), Recife, Pernambuco, Brazil
| | - Ana Lúcia Coutinho Domingues
- Postgraduate Program in Tropical Medicine, Center for Health Sciences, Universidade Federal de Pernambuco (UFPE), Recife, Pernambuco, Brazil
| | - Edmundo Pessoa de Almeida Lopes
- Postgraduate Program in Tropical Medicine, Center for Health Sciences, Universidade Federal de Pernambuco (UFPE), Recife, Pernambuco, Brazil
- Department of Internal Medicine, Hospital das Clínicas, Universidade Federal de Pernambuco (UFPE), Recife, Pernambuco, Brazil
| | - Ricardo Oliveira Silva
- Postgraduate Program in Chemistry, Fundamental Chemistry Department, Center for Exact and Natural Sciences, Universidade Federal de Pernambuco (UFPE), Recife, Pernambuco, Brazil
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Matysik S, Le Roy CI, Liebisch G, Claus SP. Metabolomics of fecal samples: A practical consideration. Trends Food Sci Technol 2016. [DOI: 10.1016/j.tifs.2016.05.011] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Haçarız O, Sayers GP. The omic approach to parasitic trematode research-a review of techniques and developments within the past 5 years. Parasitol Res 2016; 115:2523-43. [PMID: 27126082 DOI: 10.1007/s00436-016-5079-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2016] [Accepted: 04/19/2016] [Indexed: 12/26/2022]
Abstract
The evolution of technologies to explore parasite biology at a detailed level has made significant advances in recent years, particularly with the development of omic-based strategies. Whilst extensive efforts have been made in the past to develop therapeutic and prophylactic control strategies for trematode parasites, only the therapeutic anthelmintic approach can be regarded as usable in clinical practice. Currently, there is no commercialised prophylactic strategy (such as vaccination) for protection of the definitive host against any trematode parasite. Since 2010 in particular, the integration of omic technologies, including liquid chromatography-mass spectrometry (LC-MS) and next-generation sequencing (NGS), has been increasingly reported in trematode-related studies. Both LC-MS and NGS facilitate a better understanding of the biology of trematodes and provide a promising route to identifying clinically important biological characteristics of parasitic trematodes. In this review, we focus on the application, advantages, and disadvantages of omic technologies (LC-MS and NGS) in trematode research within the past 5 years and explore the use and translation of the omic-based research results into practical tools to deal with infection.
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Affiliation(s)
- Orçun Haçarız
- TÜBİTAK Marmara Research Center, Genetic Engineering and Biotechnology Institute, Gebze, Kocaeli, Turkey.
| | - Gearóid P Sayers
- Department of Science, Technology, Engineering and Mathematics, Institute of Technology Tralee, Tralee,, Co. Kerry, Ireland
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Abstract
Schistosomiasis is a major neglected tropical disease that afflicts more than 240 million people, including many children and young adults, in the tropics and subtropics. The disease is characterized by chronic infections with significant residual morbidity and is of considerable public health importance, with substantial socioeconomic impacts on impoverished communities. Morbidity reduction and eventual elimination through integrated intervention measures are the focuses of current schistosomiasis control programs. Precise diagnosis of schistosome infections, in both mammalian and snail intermediate hosts, will play a pivotal role in achieving these goals. Nevertheless, despite extensive efforts over several decades, the search for sensitive and specific diagnostics for schistosomiasis is ongoing. Here we review the area, paying attention to earlier approaches but emphasizing recent developments in the search for new diagnostics for schistosomiasis with practical applications in the research laboratory, the clinic, and the field. Careful and rigorous validation of these assays and their cost-effectiveness will be needed, however, prior to their adoption in support of policy decisions for national public health programs aimed at the control and elimination of schistosomiasis.
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Deda O, Gika HG, Wilson ID, Theodoridis GA. An overview of fecal sample preparation for global metabolic profiling. J Pharm Biomed Anal 2015; 113:137-50. [DOI: 10.1016/j.jpba.2015.02.006] [Citation(s) in RCA: 90] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2015] [Accepted: 02/05/2015] [Indexed: 01/25/2023]
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Probert F, Rice P, Scudamore CL, Wells S, Williams R, Hough TA, Cox IJ. 1H NMR Metabolic Profiling of Plasma Reveals Additional Phenotypes in Knockout Mouse Models. J Proteome Res 2015; 14:2036-45. [DOI: 10.1021/pr501039k] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Fay Probert
- Mary
Lyon Centre, MRC Harwell, Oxfordshire OX11 0RD, United Kingdom
- Institute of Hepatology, Foundation for Liver Research, 69-75 Chenies Mews, London WC1E 6HX, United Kingdom
| | - Paul Rice
- Mary
Lyon Centre, MRC Harwell, Oxfordshire OX11 0RD, United Kingdom
| | | | - Sara Wells
- Mary
Lyon Centre, MRC Harwell, Oxfordshire OX11 0RD, United Kingdom
| | - Roger Williams
- Institute of Hepatology, Foundation for Liver Research, 69-75 Chenies Mews, London WC1E 6HX, United Kingdom
| | - Tertius A. Hough
- Mary
Lyon Centre, MRC Harwell, Oxfordshire OX11 0RD, United Kingdom
| | - I. Jane Cox
- Institute of Hepatology, Foundation for Liver Research, 69-75 Chenies Mews, London WC1E 6HX, United Kingdom
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De Buck J, Shaykhutdinov R, Barkema HW, Vogel HJ. Metabolomic profiling in cattle experimentally infected with Mycobacterium avium subsp. paratuberculosis. PLoS One 2014; 9:e111872. [PMID: 25372282 PMCID: PMC4221196 DOI: 10.1371/journal.pone.0111872] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2014] [Accepted: 10/02/2014] [Indexed: 11/18/2022] Open
Abstract
The sensitivity of current diagnostics for Johne's disease, a slow, progressing enteritis in ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP), is too low to reliably detect all infected animals in the subclinical stage. The objective was to identify individual metabolites or metabolite profiles that could be used as biomarkers of early MAP infection in ruminants. In a monthly follow-up for 17 months, calves infected at 2 weeks of age were compared with aged-matched controls. Sera from all animals were analyzed by 1H nuclear magnetic resonance spectrometry. Spectra were acquired, processed, and quantified for analysis. The concentration of many metabolites changed over time in all calves, but some metabolites only changed over time in either infected or non-infected groups and the change in others was impacted by the infection. Hierarchical multivariate statistical analysis achieved best separation between groups between 300 and 400 days after infection. Therefore, a cross-sectional comparison between 1-year-old calves experimentally infected at various ages with either a high- or a low-dose and age-matched non-infected controls was performed. Orthogonal Projection to Latent Structures Discriminant Analysis (OPLS DA) yielded distinct separation of non-infected from infected cattle, regardless of dose and time (3, 6, 9 or 12 months) after infection. Receiver Operating Curves demonstrated that constructed models were high quality. Increased isobutyrate in the infected cattle was the most important agreement between the longitudinal and cross-sectional analysis. In general, high- and low-dose cattle responded similarly to infection. Differences in acetone, citrate, glycerol and iso-butyrate concentrations indicated energy shortages and increased fat metabolism in infected cattle, whereas changes in urea and several amino acids (AA), including the branched chain AA, indicated increased protein turnover. In conclusion, metabolomics was a sensitive method for detecting MAP infection much sooner than with current diagnostic methods, with individual metabolites significantly distinguishing infected from non-infected cattle.
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Affiliation(s)
- Jeroen De Buck
- Department of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada
- * E-mail:
| | - Rustem Shaykhutdinov
- Biochemistry Research Group, Department of Biological Sciences, Faculty of Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Herman W. Barkema
- Department of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Hans J. Vogel
- Biochemistry Research Group, Department of Biological Sciences, Faculty of Sciences, University of Calgary, Calgary, Alberta, Canada
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Li JV, Saric J, Yap IKS, Utzinger J, Holmes E. Metabonomic investigations of age- and batch-related variations in female NMRI mice using proton nuclear magnetic resonance spectroscopy. MOLECULAR BIOSYSTEMS 2013; 9:3155-65. [DOI: 10.1039/c3mb70215d] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
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Berrilli F, Di Cave D, Cavallero S, D'Amelio S. Interactions between parasites and microbial communities in the human gut. Front Cell Infect Microbiol 2012; 2:141. [PMID: 23162802 PMCID: PMC3499702 DOI: 10.3389/fcimb.2012.00141] [Citation(s) in RCA: 93] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2012] [Accepted: 10/29/2012] [Indexed: 12/15/2022] Open
Abstract
The interactions between intestinal microbiota, immune system, and pathogens describe the human gut as a complex ecosystem, where all components play a relevant role in modulating each other and in the maintenance of homeostasis. The balance among the gut microbiota and the human body appear to be crucial for health maintenance. Intestinal parasites, both protozoans and helminths, interact with the microbial community modifying the balance between host and commensal microbiota. On the other hand, gut microbiota represents a relevant factor that may strongly interfere with the pathophysiology of the infections. In addition to the function that gut commensal microbiota may have in the processes that determine the survival and the outcome of many parasitic infections, including the production of nutritive macromolecules, also probiotics can play an important role in reducing the pathogenicity of many parasites. On these bases, there is a growing interest in explaining the rationale on the possible interactions between the microbiota, immune response, inflammatory processes, and intestinal parasites.
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Affiliation(s)
- Federica Berrilli
- Department of Experimental Medicine and Surgery, Tor Vergata University Rome, Italy.
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