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      Beyond cells – The virome in the human holobiont

      review-article
      1 , 2 , 3 , 1 , 2 , 3 , 1 , 2 , 3 , *
      Microbial Cell
      Shared Science Publishers OG
      viral metagenomics, bacteriophages, microbiota, databases, taxonomy

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          Abstract

          Viromics, or viral metagenomics, is a relatively new and burgeoning field of research that studies the complete collection of viruses forming part of the microbiota in any given niche. It has strong foundations rooted in over a century of discoveries in the field of virology and recent advances in molecular biology and sequencing technologies. Historically, most studies have deconstructed the concept of viruses into a simplified perception of viral agents as mere pathogens, which demerits the scope of large-scale viromic analyses. Viruses are, in fact, much more than regular parasites. They are by far the most dynamic and abundant entity and the greatest killers on the planet, as well as the most effective geo-transforming genetic engineers and resource recyclers, acting on all life strata in any habitat. Yet, most of this uncanny viral world remains vastly unexplored to date, greatly hindered by the bewildering complexity inherent to such studies and the methodological and conceptual limitations. Viromic studies are just starting to address some of these issues but they still lag behind microbial metagenomics. In recent years, however, higher-throughput analysis and resequencing have rekindled interest in a field that is just starting to show its true potential. In this review, we take a look at the scientific and technological developments that led to the advent of viral and bacterial metagenomics with a particular, but not exclusive, focus on human viromics from an ecological perspective. We also address some of the most relevant challenges that current viral studies face and ponder on the future directions of the field.

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          Most cited references124

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          CRISPR provides acquired resistance against viruses in prokaryotes.

          Clustered regularly interspaced short palindromic repeats (CRISPR) are a distinctive feature of the genomes of most Bacteria and Archaea and are thought to be involved in resistance to bacteriophages. We found that, after viral challenge, bacteria integrated new spacers derived from phage genomic sequences. Removal or addition of particular spacers modified the phage-resistance phenotype of the cell. Thus, CRISPR, together with associated cas genes, provided resistance against phages, and resistance specificity is determined by spacer-phage sequence similarity.
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            Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: implications for the microbial "pan-genome".

            The development of efficient and inexpensive genome sequencing methods has revolutionized the study of human bacterial pathogens and improved vaccine design. Unfortunately, the sequence of a single genome does not reflect how genetic variability drives pathogenesis within a bacterial species and also limits genome-wide screens for vaccine candidates or for antimicrobial targets. We have generated the genomic sequence of six strains representing the five major disease-causing serotypes of Streptococcus agalactiae, the main cause of neonatal infection in humans. Analysis of these genomes and those available in databases showed that the S. agalactiae species can be described by a pan-genome consisting of a core genome shared by all isolates, accounting for approximately 80% of any single genome, plus a dispensable genome consisting of partially shared and strain-specific genes. Mathematical extrapolation of the data suggests that the gene reservoir available for inclusion in the S. agalactiae pan-genome is vast and that unique genes will continue to be identified even after sequencing hundreds of genomes.
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              The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems

              The gut-brain axis (GBA) consists of bidirectional communication between the central and the enteric nervous system, linking emotional and cognitive centers of the brain with peripheral intestinal functions. Recent advances in research have described the importance of gut microbiota in influencing these interactions. This interaction between microbiota and GBA appears to be bidirectional, namely through signaling from gut-microbiota to brain and from brain to gut-microbiota by means of neural, endocrine, immune, and humoral links. In this review we summarize the available evidence supporting the existence of these interactions, as well as the possible pathophysiological mechanisms involved. Most of the data have been acquired using technical strategies consisting in germ-free animal models, probiotics, antibiotics, and infection studies. In clinical practice, evidence of microbiota-GBA interactions comes from the association of dysbiosis with central nervous disorders (i.e. autism, anxiety-depressive behaviors) and functional gastrointestinal disorders. In particular, irritable bowel syndrome can be considered an example of the disruption of these complex relationships, and a better understanding of these alterations might provide new targeted therapies.
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                Author and article information

                Journal
                Microb Cell
                Microb Cell
                Microb Cell
                Microb Cell
                Microbial Cell
                Shared Science Publishers OG
                2311-2638
                01 July 2019
                02 September 2019
                : 6
                : 9
                : 373-396
                Affiliations
                [1 ]Institute of Evolutionary Systems Biology (I2Sysbio), Universitat de València and CSIC, València, Spain.
                [2 ]CIBER in Epidemiology and Public Health (CIBEResp), Madrid, Spain.
                [3 ]Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana (FISABIO), València, Spain.
                Author notes
                * Corresponding Author: Andrés Moya, Integrative Systems Biology Institute (I2Sysbio), University of València and Spanish Research Council (CSIC), c/ Catedrático José Beltrán 2, 46980 Paterna, València, Spain; E-mail: andres.moya@ 123456uv.es

                Conflict of interest: The authors declare that there is no conflict of interest regarding the publication of this article.

                Please cite this article as: Rodrigo García-López, Vicente Pérez-Brocal and Andrés Moya (2019). Beyond cells – The virome in the human holobiont Microbial Cell 6(9): 373-396. doi: 10.15698/mic2019.09.689

                Article
                MIC0179E109
                10.15698/mic2019.09.689
                6717880
                31528630
                02834575-e7bb-4146-bc52-3b8356df7ee5
                Copyright @ 2019

                This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.

                History
                : 21 January 2019
                : 14 March 2019
                : 03 April 2019
                Funding
                This work was supported by grants to AM from the Spanish Ministry of Economy and Competitiveness (projects SAF2012-31187, SAF2013-49788-EXP, SAF2015-65878-R), Carlos III Institute of Health (projects PIE14/00045 and AC15/00022), Generalitat Valenciana (project PrometeoII/2014/065 and Prometeo/2018/A/133), Asociación Española contra el Cancer (project AECC 2017-1485) and co-financed by the European Regional Development Fund (ERDF).
                Categories
                Review
                Viral Metagenomics
                Bacteriophages
                Microbiota
                Databases
                Taxonomy

                viral metagenomics,bacteriophages,microbiota,databases,taxonomy

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