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      Application of Volatilome Analysis to the Diagnosis of Mycobacteria Infection in Livestock

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          Abstract

          Volatile organic compounds (VOCs) are small molecular mass metabolites which compose the volatilome, whose analysis has been widely employed in different areas. This innovative approach has emerged in research as a diagnostic alternative to different diseases in human and veterinary medicine, which still present constraints regarding analytical and diagnostic sensitivity. Such is the case of the infection by mycobacteria responsible for tuberculosis and paratuberculosis in livestock. Although eradication and control programs have been partly managed with success in many countries worldwide, the often low sensitivity of the current diagnostic techniques against Mycobacterium bovis (as well as other mycobacteria from Mycobacterium tuberculosis complex) and Mycobacterium avium subsp. paratuberculosis together with other hurdles such as low mycobacteria loads in samples, a tedious process of microbiological culture, inhibition by many variables, or intermittent shedding of the mycobacteria highlight the importance of evaluating new techniques that open different options and complement the diagnostic paradigm. In this sense, volatilome analysis stands as a potential option because it fulfills part of the mycobacterial diagnosis requirements. The aim of the present review is to compile the information related to the diagnosis of tuberculosis and paratuberculosis in livestock through the analysis of VOCs by using different biological matrices. The analytical techniques used for the evaluation of VOCs are discussed focusing on the advantages and drawbacks offered compared with the routine diagnostic tools. In addition, the differences described in the literature among in vivo and in vitro assays, natural and experimental infections, and the use of specific VOCs (targeted analysis) and complete VOC pattern (non-targeted analysis) are highlighted. This review emphasizes how this methodology could be useful in the problematic diagnosis of tuberculosis and paratuberculosis in livestock and poses challenges to be addressed in future research.

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          HMDB: a knowledgebase for the human metabolome

          The Human Metabolome Database (HMDB, http://www.hmdb.ca) is a richly annotated resource that is designed to address the broad needs of biochemists, clinical chemists, physicians, medical geneticists, nutritionists and members of the metabolomics community. Since its first release in 2007, the HMDB has been used to facilitate the research for nearly 100 published studies in metabolomics, clinical biochemistry and systems biology. The most recent release of HMDB (version 2.0) has been significantly expanded and enhanced over the previous release (version 1.0). In particular, the number of fully annotated metabolite entries has grown from 2180 to more than 6800 (a 300% increase), while the number of metabolites with biofluid or tissue concentration data has grown by a factor of five (from 883 to 4413). Similarly, the number of purified compounds with reference to NMR, LC-MS and GC-MS spectra has more than doubled (from 380 to more than 790 compounds). In addition to this significant expansion in database size, many new database searching tools and new data content has been added or enhanced. These include better algorithms for spectral searching and matching, more powerful chemical substructure searches, faster text searching software, as well as dedicated pathway searching tools and customized, clickable metabolic maps. Changes to the user-interface have also been implemented to accommodate future expansion and to make database navigation much easier. These improvements should make the HMDB much more useful to a much wider community of users.
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            Gut flora in health and disease.

            The human gut is the natural habitat for a large and dynamic bacterial community, but a substantial part of these bacterial populations are still to be described. However, the relevance and effect of resident bacteria on a host's physiology and pathology has been well documented. Major functions of the gut microflora include metabolic activities that result in salvage of energy and absorbable nutrients, important trophic effects on intestinal epithelia and on immune structure and function, and protection of the colonised host against invasion by alien microbes. Gut flora might also be an essential factor in certain pathological disorders, including multisystem organ failure, colon cancer, and inflammatory bowel diseases. Nevertheless, bacteria are also useful in promotion of human health. Probiotics and prebiotics are known to have a role in prevention or treatment of some diseases.
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              HMDB 3.0—The Human Metabolome Database in 2013

              The Human Metabolome Database (HMDB) (www.hmdb.ca) is a resource dedicated to providing scientists with the most current and comprehensive coverage of the human metabolome. Since its first release in 2007, the HMDB has been used to facilitate research for nearly 1000 published studies in metabolomics, clinical biochemistry and systems biology. The most recent release of HMDB (version 3.0) has been significantly expanded and enhanced over the 2009 release (version 2.0). In particular, the number of annotated metabolite entries has grown from 6500 to more than 40 000 (a 600% increase). This enormous expansion is a result of the inclusion of both ‘detected’ metabolites (those with measured concentrations or experimental confirmation of their existence) and ‘expected’ metabolites (those for which biochemical pathways are known or human intake/exposure is frequent but the compound has yet to be detected in the body). The latest release also has greatly increased the number of metabolites with biofluid or tissue concentration data, the number of compounds with reference spectra and the number of data fields per entry. In addition to this expansion in data quantity, new database visualization tools and new data content have been added or enhanced. These include better spectral viewing tools, more powerful chemical substructure searches, an improved chemical taxonomy and better, more interactive pathway maps. This article describes these enhancements to the HMDB, which was previously featured in the 2009 NAR Database Issue. (Note to referees, HMDB 3.0 will go live on 18 September 2012.).
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                Author and article information

                Contributors
                Journal
                Front Vet Sci
                Front Vet Sci
                Front. Vet. Sci.
                Frontiers in Veterinary Science
                Frontiers Media S.A.
                2297-1769
                24 May 2021
                2021
                : 8
                : 635155
                Affiliations
                [1] 1Department of Animal Production, International Agrifood Campus of Excellence (ceiA3), University of Córdoba , Córdoba, Spain
                [2] 2Department of Analytical Chemistry, Inst Univ Invest Quim Fina and Nanoquim Inst Univ Invest Quim Fina and Nanoquim (IUNAN), International Agrifood Campus of Excellence (ceiA3), University of Córdoba , Córdoba, Spain
                [3] 3Department of Anatomy and Comparative Pathology and Toxicology, International Agrifood Campus of Excellence (ceiA3), University of Córdoba , Córdoba, Spain
                Author notes

                Edited by: Anuwat Wiratsudakul, Mahidol University, Thailand

                Reviewed by: Douwe Bakker, Independent Researcher, Lelystad, Netherlands; Wolfram Miekisch, University Hospital Rostock, Germany

                *Correspondence: Jaime Gómez-Laguna j.gomez-laguna@ 123456uco.es

                This article was submitted to Veterinary Epidemiology and Economics, a section of the journal Frontiers in Veterinary Science

                Article
                10.3389/fvets.2021.635155
                8180594
                34109231
                1d67ca76-e73b-4b36-9423-eedc66bb3f45
                Copyright © 2021 Rodríguez-Hernández, Rodríguez-Estévez, Arce and Gómez-Laguna.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 29 November 2020
                : 08 April 2021
                Page count
                Figures: 0, Tables: 3, Equations: 0, References: 118, Pages: 14, Words: 11321
                Funding
                Funded by: Ministerio de Economía y Competitividad 10.13039/501100003329
                Funded by: Universidad de Córdoba 10.13039/501100008679
                Categories
                Veterinary Science
                Review

                diagnosis,livestock,mycobacteria,volatilome,veterinary
                diagnosis, livestock, mycobacteria, volatilome, veterinary

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