{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T10:13:52Z","timestamp":1791627232511,"version":"4.3.4"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":103,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"VENTRIS","award":["n\u00b0ANR-21-CE14-0019-01"],"award-info":[{"award-number":["n\u00b0ANR-21-CE14-0019-01"]}]},{"DOI":"10.13039\/501100001665","name":"French National Research Agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale and Sorbonne Universit\u00e9"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Reactive oxygen species (ROS) are essential for cellular signalling and redox homeostasis, but their accumulation causes cellular oxidative stress. In inflammatory bowel disease, oxidative stress is linked to chronic inflammation and alterations in the gut microbiota. We hypothesised that these alterations may result from the impact of ROS on the interactions between bacteria and their viruses, bacteriophages. We followed the evolution of three Escherichia coli strains and a virulent bacteriophage in a chemostat under continuous growth and studied the impact of oxidative stress on this community. We show that both the bacteriophage and its three hosts persisted in the system over 10\u00a0days, but the relative abundance of bacteriophages was decreased in the presence of ROS. Oxidative stress also limited bacteriophage population diversity by favouring the selection of specialist bacteriophages with a narrower host range. Concomitantly, ROS accelerated the evolution of bacterial resistance to bacteriophages and drove the fixation of genomic mutations in genes related to cell surface structures or located in mobile genetic elements. These results highlight that oxidative stress impacts the evolutionary dynamics between bacteria and bacteriophages with consequences for microbiota diversity and potential implications in the context of intestinal inflammation.<\/jats:p>","DOI":"10.1093\/ismejo\/wrag090","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T11:23:40Z","timestamp":1776079420000},"source":"Crossref","is-referenced-by-count":1,"title":["Oxidative stress constrains evolution of bacteriophage host-range diversity"],"prefix":"10.1093","volume":"20","author":[{"given":"Coline","family":"Meynard-Doumenc","sequence":"first","affiliation":[{"name":"INSERM, Centre de Recherche Saint-Antoine, Sorbonne Universit\u00e9 , 75012 Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7141-6340","authenticated-orcid":false,"given":"Quentin","family":"Lamy-Besnier","sequence":"additional","affiliation":[{"name":"INSERM, Centre de Recherche Saint-Antoine, Sorbonne Universit\u00e9 , 75012 Paris ,","place":["France"]},{"name":"INRAE, MICALIS Unit, Universit\u00e9 Paris-Saclay , 78352 Jouy-en-Josas ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6977-4253","authenticated-orcid":false,"given":"Lo\u00efc","family":"Brot","sequence":"additional","affiliation":[{"name":"INSERM, Centre de Recherche Saint-Antoine, Sorbonne Universit\u00e9 , 75012 Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Messika","sequence":"additional","affiliation":[{"name":"INSERM, Centre de Recherche Saint-Antoine, Sorbonne Universit\u00e9 , 75012 Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Auguste","family":"Wolfromm","sequence":"additional","affiliation":[{"name":"INSERM, Centre de Recherche Saint-Antoine, Sorbonne Universit\u00e9 , 75012 Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9434-3706","authenticated-orcid":false,"given":"Jean-Pierre","family":"Grill","sequence":"additional","affiliation":[{"name":"INSERM, Centre de Recherche Saint-Antoine, Sorbonne Universit\u00e9 , 75012 Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3785-550X","authenticated-orcid":false,"given":"Luisa","family":"De Sordi","sequence":"additional","affiliation":[{"name":"INSERM, Centre de Recherche Saint-Antoine, Sorbonne Universit\u00e9 , 75012 Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"2026050811305626500_ref1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1083\/jcb.201102095","article-title":"Signal transduction by reactive oxygen species","volume":"194","author":"Finkel","year":"2011","journal-title":"J Cell Biol"},{"key":"2026050811305626500_ref2","doi-asserted-by":"publisher","first-page":"R453","DOI":"10.1016\/j.cub.2014.03.034","article-title":"ROS function in redox signaling and oxidative stress","volume":"24","author":"Schieber","year":"2014","journal-title":"Curr Biol"},{"key":"2026050811305626500_ref3","doi-asserted-by":"publisher","first-page":"459","DOI":"10.33549\/physiolres.931844","article-title":"Some current insights into oxidative stress","volume":"59","author":"Durackova","year":"2009","journal-title":"Physiol Res Acad Sci Bohemoslov"},{"key":"2026050811305626500_ref4","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1016\/S0016-5085(98)70019-8","article-title":"Presence of adherent Escherichia coli strains in ileal mucosa of patients with Crohn\u2019s disease","volume":"115","author":"Darfeuille-Michaud","year":"1998","journal-title":"Gastroenterology"},{"key":"2026050811305626500_ref5","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1038\/nrgastro.2012.152","article-title":"The gut microbiota in IBD","volume":"9","author":"Manichanh","year":"2012","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"2026050811305626500_ref6","doi-asserted-by":"publisher","first-page":"16731","DOI":"10.1073\/pnas.0804812105","article-title":"Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients","volume":"105","author":"Sokol","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026050811305626500_ref7","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1097\/01.MIB.0000200323.38139.c6","article-title":"Specificities of the fecal microbiota in inflammatory bowel disease","volume":"12","author":"Sokol","year":"2006","journal-title":"Inflamm Bowel Dis"},{"key":"2026050811305626500_ref8","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.abb.2012.02.007","article-title":"Regulators of oxidative stress response genes in Escherichia coli and their functional conservation in bacteria","volume":"525","author":"Chiang","year":"2012","journal-title":"Arch Biochem Biophys"},{"key":"2026050811305626500_ref9","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1111\/1462-2920.14445","article-title":"Where in the world do bacteria experience oxidative stress?","volume":"21","author":"Imlay","year":"2019","journal-title":"Environ Microbiol"},{"key":"2026050811305626500_ref10","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1038\/nrmicro.2017.26","article-title":"Oxidative stress, protein damage and repair in bacteria","volume":"15","author":"Ezraty","year":"2017","journal-title":"Nat Rev Microbiol"},{"key":"2026050811305626500_ref11","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1126\/science.adi5536","article-title":"Rapid bacteria-phage coevolution drives the emergence of multiscale networks","volume":"382","author":"Borin","year":"2023","journal-title":"Science"},{"key":"2026050811305626500_ref12","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1038\/s41586-019-1894-8","article-title":"The arms race between bacteria and their phage foes","volume":"577","author":"Hampton","year":"2020","journal-title":"Nature"},{"key":"2026050811305626500_ref13","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1098\/rspb.2001.1945","article-title":"Antagonistic coevolution between a bacterium and a bacteriophage","volume":"269","author":"Buckling","year":"2002","journal-title":"Proc R Soc B Biol Sci"},{"key":"2026050811305626500_ref14","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1111\/1574-6976.12072","article-title":"Bacteria\u2013phage coevolution as a driver of ecological and evolutionary processes in microbial communities","volume":"38","author":"Koskella","year":"2014","journal-title":"FEMS Microbiol Rev"},{"key":"2026050811305626500_ref15","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/S0022-5193(84)80035-1","article-title":"Coevolution of bacteria and phage: are there endless cycles of bacterial defenses and phage counterdefenses?","volume":"108","author":"Lenski","year":"1984","journal-title":"J Theor Biol"},{"key":"2026050811305626500_ref16","doi-asserted-by":"publisher","first-page":"1616","DOI":"10.1101\/gr.122705.111","article-title":"The human gut virome: inter-individual variation and dynamic response to diet","volume":"21","author":"Minot","year":"2011","journal-title":"Genome Res"},{"key":"2026050811305626500_ref17","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/j.chom.2019.09.009","article-title":"The human gut virome is highly diverse, stable, and individual specific","volume":"26","author":"Shkoporov","year":"2019","journal-title":"Cell Host Microbe"},{"key":"2026050811305626500_ref18","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1016\/j.chom.2020.06.002","article-title":"The spatial heterogeneity of the gut limits predation and fosters coexistence of bacteria and bacteriophages","volume":"28","author":"Louren\u00e7o","year":"2020","journal-title":"Cell Host Microbe"},{"key":"2026050811305626500_ref19","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/j.chom.2022.03.014","article-title":"The gut environment regulates bacterial gene expression which modulates susceptibility to bacteriophage infection","volume":"30","author":"Louren\u00e7o","year":"2022","journal-title":"Cell Host Microbe"},{"key":"2026050811305626500_ref20","doi-asserted-by":"publisher","first-page":"1955","DOI":"10.3390\/v13101955","article-title":"Reduced infection efficiency of phage NCTC 12673 on non-motile campylobacter jejuni strains is related to oxidative stress","volume":"13","author":"Sacher","year":"2021","journal-title":"Viruses"},{"key":"2026050811305626500_ref21","doi-asserted-by":"publisher","first-page":"101437","DOI":"10.1016\/j.isci.2020.101437","article-title":"Transcriptomic analysis reveals the dependency of Pseudomonas aeruginosa genes for double-stranded RNA bacteriophage phiYY infection cycle","volume":"23","author":"Zhong","year":"2020","journal-title":"iScience"},{"key":"2026050811305626500_ref22","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1126\/science.adl3222","article-title":"Prophage terminase with tRNase activity sensitizes Salmonella enterica to oxidative stress","volume":"384","author":"Uppalapati","year":"2024","journal-title":"Science"},{"key":"2026050811305626500_ref23","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/s41579-021-00602-y","article-title":"Interactions between bacterial and phage communities in natural environments","volume":"20","author":"Chevallereau","year":"2022","journal-title":"Nat Rev Microbiol"},{"key":"2026050811305626500_ref24","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1016\/j.chom.2017.10.010","article-title":"The gut microbiota facilitates drifts in the genetic diversity and infectivity of bacterial viruses","volume":"22","author":"De Sordi","year":"2017","journal-title":"Cell Host Microbe"},{"key":"2026050811305626500_ref25","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1093\/ecco-jcc\/jjw224","article-title":"Bacteriophages targeting adherent invasive Escherichia coli strains as a promising new treatment for Crohn\u2019s disease","volume":"11","author":"Galtier","year":"2017","journal-title":"J Crohns Colitis"},{"key":"2026050811305626500_ref26","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1007\/978-1-60327-164-6_18","volume-title":"Bacteriophages, Methods in Molecular Biology","author":"Hyman","year":"2009"},{"key":"2026050811305626500_ref27","doi-asserted-by":"publisher","first-page":"6968","DOI":"10.1038\/s41467-022-34630-w","article-title":"Muscle5: high-accuracy alignment ensembles enable unbiased assessments of sequence homology and phylogeny","volume":"13","author":"Edgar","year":"2022","journal-title":"Nat Commun"},{"key":"2026050811305626500_ref28","doi-asserted-by":"publisher","first-page":"834406","DOI":"10.3389\/fcimb.2022.834406","article-title":"Greater phage genotypic diversity constrains arms-race coevolution","volume":"12","author":"Castledine","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"key":"2026050811305626500_ref29","doi-asserted-by":"publisher","first-page":"e616","DOI":"10.7717\/peerj.616","article-title":"Using observation-level random effects to model overdispersion in count data in ecology and evolution","volume":"2","author":"Harrison","year":"2014","journal-title":"PeerJ"},{"key":"2026050811305626500_ref30","author":"R Core Team"},{"key":"2026050811305626500_ref31","doi-asserted-by":"publisher","author":"Bates","DOI":"10.18637\/jss.v067.i01"},{"key":"2026050811305626500_ref32","doi-asserted-by":"publisher","first-page":"000685","DOI":"10.1099\/mgen.0.000685","article-title":"Bakta: rapid and standardized annotation of bacterial genomes via alignment-free sequence identification","volume":"7","author":"Schwengers","year":"2021","journal-title":"Microb Genomics"},{"key":"2026050811305626500_ref33","doi-asserted-by":"publisher","first-page":"btac776","DOI":"10.1093\/bioinformatics\/btac776","article-title":"Pharokka: a fast scalable bacteriophage annotation tool","volume":"39","author":"Bouras","year":"2023","journal-title":"Bioinformatics"},{"key":"2026050811305626500_ref34","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1038\/s41587-023-01953-y","article-title":"Identification of mobile genetic elements with geNomad","volume":"42","author":"Camargo","year":"2024","journal-title":"Nat Biotechnol"},{"key":"2026050811305626500_ref35","doi-asserted-by":"publisher","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"Fastp: an ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"2026050811305626500_ref36","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1186\/1471-2164-15-1039","article-title":"Identifying structural variation in haploid microbial genomes from short-read resequencing data using breseq","volume":"15","author":"Barrick","year":"2014","journal-title":"BMC Genomics"},{"key":"2026050811305626500_ref37","doi-asserted-by":"publisher","first-page":"2847","DOI":"10.1038\/s41564-024-01832-5","article-title":"Prediction of strain level phage\u2013host interactions across the Escherichia genus using only genomic information","volume":"9","author":"Gaborieau","year":"2024","journal-title":"Nat Microbiol"},{"key":"2026050811305626500_ref38","doi-asserted-by":"publisher","first-page":"112305","DOI":"10.1016\/j.celrep.2023.112305","article-title":"Bacteriophage antidefense genes that neutralize TIR and STING immune responses","volume":"42","author":"Ho","year":"2023","journal-title":"Cell Rep"},{"key":"2026050811305626500_ref39","doi-asserted-by":"publisher","first-page":"9586","DOI":"10.1038\/s41467-024-53789-y","article-title":"Evasion of antiviral bacterial immunity by phage tRNAs","volume":"15","author":"Azam","year":"2024","journal-title":"Nat Commun"},{"key":"2026050811305626500_ref40","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1038\/s41586-024-07874-3","article-title":"A virally encoded tRNA neutralizes the PARIS antiviral defence system","volume":"634","author":"Burman","year":"2024","journal-title":"Nature"},{"key":"2026050811305626500_ref41","doi-asserted-by":"publisher","first-page":"3119","DOI":"10.1038\/s41396-021-01012-x","article-title":"Community context matters for bacteria-phage ecology and evolution","volume":"15","author":"Blazanin","year":"2021","journal-title":"ISME J"},{"key":"2026050811305626500_ref42","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1126\/science.1214449","article-title":"Repeatability and contingency in the evolution of a key innovation in phage lambda","volume":"335","author":"Meyer","year":"2012","journal-title":"Science"},{"key":"2026050811305626500_ref43","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1038\/s41559-020-01364-1","article-title":"Host diversity slows bacteriophage adaptation by selecting generalists over specialists","volume":"5","author":"Sant","year":"2021","journal-title":"Nat Ecol Evol"},{"key":"2026050811305626500_ref44","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1038\/s41579-022-00755-4","article-title":"Mutualistic interplay between bacteriophages and bacteria in the human gut","volume":"20","author":"Shkoporov","year":"2022","journal-title":"Nat Rev Microbiol"},{"key":"2026050811305626500_ref45","doi-asserted-by":"publisher","first-page":"101201","DOI":"10.1016\/j.coviro.2022.101201","article-title":"Mitigation of evolved bacterial resistance to phage therapy","volume":"53","author":"Torres-Barcel\u00f3","year":"2022","journal-title":"Curr Opin Virol"},{"key":"2026050811305626500_ref46","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.tim.2018.08.006","article-title":"Molecular and evolutionary determinants of bacteriophage host range","volume":"27","author":"Jonge","year":"2019","journal-title":"Trends Microbiol"},{"key":"2026050811305626500_ref47","doi-asserted-by":"publisher","first-page":"E149","DOI":"10.1086\/528962","article-title":"Optimal foraging by bacteriophages through host avoidance","volume":"171","author":"Heineman","year":"2008","journal-title":"Am Nat"},{"key":"2026050811305626500_ref48","doi-asserted-by":"publisher","first-page":"e113078","DOI":"10.1371\/journal.pone.0113078","article-title":"Frequency and fitness consequences of bacteriophage \u03a66 host range mutations","volume":"9","author":"Ford","year":"2014","journal-title":"PLoS One"},{"key":"2026050811305626500_ref49","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1136\/gut.52.2.237","article-title":"Alterations of the dominant faecal bacterial groups in patients with Crohn\u2019s disease of the colon","volume":"52","author":"Seksik","year":"2003","journal-title":"Gut"},{"key":"2026050811305626500_ref50","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1016\/j.chom.2019.10.009","article-title":"Whole-virome analysis sheds light on viral dark matter in inflammatory bowel disease","volume":"26","author":"Clooney","year":"2019","journal-title":"Cell Host Microbe"},{"key":"2026050811305626500_ref51","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1136\/gut.2005.073817","article-title":"Reduced diversity of faecal microbiota in Crohn\u2019s disease revealed by a metagenomic approach","volume":"55","author":"Manichanh","year":"2006","journal-title":"Gut"},{"key":"2026050811305626500_ref52","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1136\/gutjnl-2016-313235","article-title":"A microbial signature for Crohn\u2019s disease","volume":"66","author":"Pascal","year":"2017","journal-title":"Gut"},{"key":"2026050811305626500_ref53","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/s42003-023-04592-w","article-title":"Interpersonal variability of the human gut virome confounds disease signal detection in IBD","volume":"6","author":"Stockdale","year":"2023","journal-title":"Commun Biol"},{"key":"2026050811305626500_ref54","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1053\/j.gastro.2025.10.007","article-title":"The human blood virome differs in Crohn\u2019s disease","volume":"170","author":"Lamy-Besnier","year":"2026","journal-title":"Gastroenterology"},{"key":"2026050811305626500_ref55","doi-asserted-by":"publisher","first-page":"R923","DOI":"10.1016\/j.cub.2022.07.075","article-title":"Bacterial immunity: mobile genetic elements are hotspots for defence systems","volume":"32","author":"Chevallereau","year":"2022","journal-title":"Curr Biol"}],"container-title":["The ISME Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ismej\/advance-article-pdf\/doi\/10.1093\/ismejo\/wrag090\/68079322\/wrag090.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ismej\/article-pdf\/20\/1\/wrag090\/68079322\/wrag090.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ismej\/article-pdf\/20\/1\/wrag090\/68079322\/wrag090.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T15:31:03Z","timestamp":1778254263000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ismej\/article\/doi\/10.1093\/ismejo\/wrag090\/8653884"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":55,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1,14]]}},"URL":"https:\/\/doi.org\/10.1093\/ismejo\/wrag090","relation":{},"ISSN":["1751-7362","1751-7370"],"issn-type":[{"value":"1751-7362","type":"print"},{"value":"1751-7370","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,1]]},"published":{"date-parts":[[2026,1]]},"article-number":"wrag090"}}