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      Phage-mediated horizontal gene transfer and its implications for the human gut microbiome

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          Abstract

          Horizontal gene transfer (HGT) in the microbiome has profound consequences for human health and disease. The spread of antibiotic resistance genes, virulence, and pathogenicity determinants predominantly occurs by way of HGT. Evidence exists of extensive horizontal transfer in the human gut microbiome. Phage transduction is a type of HGT event in which a bacteriophage transfers non-viral DNA from one bacterial host cell to another. The abundance of tailed bacteriophages in the human gut suggests that transduction could act as a significant mode of HGT in the gut microbiome. Here we review in detail the known mechanisms of phage-mediated HGT, namely specialized and generalized transduction, lateral transduction, gene-transfer agents, and molecular piracy, as well as methods used to detect phage-mediated HGT, and discuss its potential implications for the human gut microbiome.

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          Horizontal gene transfer: building the web of life.

          Horizontal gene transfer (HGT) is the sharing of genetic material between organisms that are not in a parent-offspring relationship. HGT is a widely recognized mechanism for adaptation in bacteria and archaea. Microbial antibiotic resistance and pathogenicity are often associated with HGT, but the scope of HGT extends far beyond disease-causing organisms. In this Review, we describe how HGT has shaped the web of life using examples of HGT among prokaryotes, between prokaryotes and eukaryotes, and even between multicellular eukaryotes. We discuss replacement and additive HGT, the proposed mechanisms of HGT, selective forces that influence HGT, and the evolutionary impact of HGT on ancestral populations and existing populations such as the human microbiome.
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            Bacteriophages of the Human Gut: The “Known Unknown” of the Microbiome

            The human gut microbiome is a dense and taxonomically diverse consortium of microorganisms. While the bacterial components of the microbiome have received considerable attention, comparatively little is known about the composition and physiological significance of human gut-associated bacteriophage populations (phageome). By extrapolating our knowledge of phage-host interactions from other environments, one could expect that >1012 viruses reside in the human gut, and we can predict that they play important roles in regulating the complex microbial networks operating in this habitat. Before delving into their function, we need to first overcome the challenges associated with studying and characterizing the phageome. In this Review, we summarize the available methods and main findings regarding taxonomic composition, community structure, and population dynamics in the human gut phageome. We also discuss the main challenges in the field and identify promising avenues for future research.
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              Antibiotic Treatment Expands the Resistance Reservoir and Ecological Network of the Phage Metagenome

              The mammalian gut ecosystem has significant influence on host physiology 1–4 , but the mechanisms that sustain this complex environment in the face of different stresses remain obscure. Perturbations to this ecosystem, such as through antibiotic treatment or diet, are currently interpreted at the level of bacterial phylogeny 5–7 . Less is known about the contributions of the abundant population of phage to this ecological network. Here, we explore the phageome as a potential genetic reservoir for bacterial adaptation by sequencing murine fecal phage populations following antibiotic perturbation. We show that antibiotic treatment leads to the enrichment of phage-encoded genes that confer resistance via disparate mechanisms to the administered drug as well as genes that confer resistance to antibiotics unrelated to the administered drug, and we demonstrate experimentally that phage from treated mice afford aerobically cultured naïve microbiota increased resistance. Systems-wide analyses uncover post-treatment phage-encoded processes related to host colonization and growth adaptation, indicating that the phageome broadly enriches for functionally beneficial genes under stress-related conditions. We also show that antibiotic treatment expands the interactions between phage and bacterial species, leading to a more highly connected phage-bacterial network for gene exchange. Our work implicates the phageome in the emergence of multidrug resistance and indicates that the adaptive capacity of the phageome may represent a community-based mechanism for protecting the gut microflora, preserving its functional robustness during antibiotic stress.
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                Author and article information

                Journal
                Gastroenterol Rep (Oxf)
                Gastroenterol Rep (Oxf)
                gastro
                Gastroenterology Report
                Oxford University Press
                2052-0034
                2022
                13 April 2022
                13 April 2022
                : 10
                : goac012
                Affiliations
                [1 ] APC Microbiome Ireland, University College Cork , Cork, Ireland
                [2 ] School of Microbiology, University College Cork , Cork, Ireland
                Author notes
                Corresponding author. APC Microbiome Ireland, Biosciences Institute, University College Cork, Room 3.63, College Road, Cork, T12 YT20, Ireland. Email: Tatiana.Borodovich@ 123456umail.ucc.ie
                Author information
                https://orcid.org/0000-0002-0183-6251
                https://orcid.org/0000-0002-8527-1445
                Article
                goac012
                10.1093/gastro/goac012
                9006064
                35425613
                6921a937-2bf9-4ffa-9545-d144a90c9e04
                © The Author(s) 2022. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 December 2021
                : 08 February 2022
                : 04 March 2022
                Page count
                Pages: 12
                Funding
                Funded by: Science Foundation Ireland, DOI 10.13039/501100001602;
                Award ID: SFI/12/RC/2273_P2
                Funded by: Wellcome Trust Research Career Development Fellowship;
                Award ID: 220646/Z/20/Z
                Categories
                Review Article
                AcademicSubjects/MED00260

                gut phageome,horizontal gene transfer,gene transduction,phage-mediated gene transfer

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