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      Characterizing the gut phageome and phage-borne antimicrobial resistance genes in pigs

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          Abstract

          Background

          Mammalian intestine harbors a mass of phages that play important roles in maintaining gut microbial ecosystem and host health. Pig has become a common model for biomedical research and provides a large amount of meat for human consumption. However, the knowledge of gut phages in pigs is still limited.

          Results

          Here, we investigated the gut phageome in 112 pigs from seven pig breeds using PhaBOX strategy based on the metagenomic data. A total of 174,897 non-redundant gut phage genomes were assembled from 112 metagenomes. A total of 33,487 gut phage genomes were classified and these phages mainly belonged to phage families such as Ackermannviridae, Straboviridae, Peduoviridae, Zierdtviridae, Drexlerviridae, and Herelleviridae. The gut phages in seven pig breeds exhibited distinct communities and the gut phage communities changed with the age of pig. These gut phages were predicted to infect a broad range of 212 genera of prokaryotes, such as Candidatus Hamiltonella, Mycoplasma, Colwellia, and Lactobacillus. The data indicated that broad KEGG and CAZy functions were also enriched in gut phages of pigs. The gut phages also carried the antimicrobial resistance genes (ARGs) and the most abundant antimicrobial resistance genotype was diaminopyrimidine resistance.

          Conclusions

          Our research delineates a landscape for gut phages in seven pig breeds and reveals that gut phages serve as a key reservoir of ARGs in pigs.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s40168-024-01818-9.

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          Most cited references62

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          Explaining microbial population genomics through phage predation.

          The remarkable differences that have been detected by metagenomics in the genomes of strains of the same bacterial species are difficult to reconcile with the widely accepted paradigm that periodic selection within bacterial populations will regularly purge genomic diversity by clonal replacement. We have found that many of the genes that differ between strains affect regions that are potential phage recognition targets. We therefore propose the constant-diversity dynamics model, in which the diversity of prokaryotic populations is preserved by phage predation. We provide supporting evidence for this model from metagenomics, mathematical analysis and computer simulations. Periodic selection and phage predation dynamics are not mutually exclusive; we compare their predictions to shed light on the ecological circumstances under which each type of dynamics could predominate.
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            Phage diversity, genomics and phylogeny

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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

                Contributors
                xhyan@mail.hzau.edu.cn
                Journal
                Microbiome
                Microbiome
                Microbiome
                BioMed Central (London )
                2049-2618
                5 June 2024
                5 June 2024
                2024
                : 12
                : 102
                Affiliations
                [1 ]GRID grid.35155.37, ISNI 0000 0004 1790 4137, National Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, Frontiers Science Center for Animal Breeding and Sustainable Production, College of Animal Sciences and Technology, , Huazhong Agricultural University, ; Wuhan, Hubei 430070 China
                [2 ]College of Animal Sciences, Fujian Agriculture and Forestry University, ( https://ror.org/04kx2sy84) Fuzhou, Fujian 350002 China
                [3 ]GRID grid.35155.37, ISNI 0000 0004 1790 4137, The Cooperative Innovation Center for Sustainable Pig Production, ; Wuhan, Hubei 430070 China
                [4 ]Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, Hubei 430070 China
                [5 ]BGI Research, ( https://ror.org/05gsxrt27) Qingdao, Shandong 266555 China
                [6 ]Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, ( https://ror.org/035b05819) Copenhagen, 2100 Denmark
                Article
                1818
                10.1186/s40168-024-01818-9
                11151549
                38840247
                09acab0d-4d7e-4264-ad89-2847c9602ffe
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 30 December 2023
                : 18 April 2024
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 32102499
                Award ID: 31925037
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100012152, National Postdoctoral Program for Innovative Talents;
                Award ID: BX20190133
                Award Recipient :
                Funded by: Postdoctoral Science Foundation of China
                Award ID: 2019M662671
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100003819, Natural Science Foundation of Hubei Province;
                Award ID: 2022CFB358
                Award Recipient :
                Categories
                Research
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                © BioMed Central Ltd., part of Springer Nature 2024

                pig,metagenomic,gut phageome,phabox,antimicrobial resistance genes

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