Camarillo-Guerrero, L. F., Almeida, A., Rangel-Pineros, G., Finn, R. D. & Lawley, T. D. Massive expansion of human gut bacteriophage diversity. Cell 184, 1098–1109 (2021).
Nayfach, S. et al. Metagenomic compendium of 189,680 DNA viruses from the human gut microbiome. Nat. Microbiol. 6, 960–970 (2021).
Gregory, A. C. et al. The Gut Virome Database reveals age-dependent patterns of virome diversity in the human gut. Cell Host Microbe 28, 724–740 (2020).
Clooney, A. G. et al. Whole-virome analysis sheds light on viral dark matter in inflammatory bowel disease. Cell Host Microbe 26, 764–778 (2019).
Gogokhia, L. et al. Expansion of bacteriophages is linked to aggravated intestinal inflammation and colitis. Cell Host Microbe 25, 285–299 (2019).
Rodriguez-Valera, F. et al. Explaining microbial population genomics through phage predation. Nat. Rev. Microbiol. 7, 828–836 (2009).
Chevallereau, A., Pons, B. J., van Houte, S. & Westra, E. R. Interactions between bacterial and phage communities in natural environments. Nat. Rev. Microbiol. 20, 49–62 (2022).
Zuo, T. et al. Human-gut-DNA virome variations across geography, ethnicity, and urbanization. Cell Host Microbe 28, 741–751 (2020).
Benler, S. et al. Thousands of previously unknown phages discovered in whole-community human gut metagenomes. Microbiome 9, 78 (2021).
Van Espen, L. et al. A previously undescribed highly prevalent phage identified in a Danish enteric virome catalog. mSystems 6, e0038221 (2021).
Govier, T. & Verwoerd, W. The promise and pitfalls of prophages. Preprint at bioRxiv https://doi.org/10.1101/2023.04.20.537752 (2023).
Anthenelli, M. et al. Phage and bacteria diversification through a prophage acquisition ratchet. Preprint at bioRxiv https://doi.org/10.1101/2020.04.08.028340 (2020).
Bobay, L. M., Touchon, M. & Rocha, E. P. C. Pervasive domestication of defective prophages by bacteria. Proc. Natl Acad. Sci. USA 111, 12127–12132 (2014).
Wang, X. et al. Cryptic prophages help bacteria cope with adverse environments. Nat. Commun. 1, 147–149 (2010).
Erez, Z. et al. Communication between viruses guides lysis-lysogeny decisions. Nature 541, 488–493 (2017).
Silpe, J. E., Duddy, O. P. & Bassler, B. L. Natural and synthetic inhibitors of a phage-encoded quorum-sensing receptor affect phage–host dynamics in mixed bacterial communities. Proc. Natl Acad. Sci. USA 119, e2217813119 (2022).
Browne, H. P. et al. Culturing of ‘unculturable’ human microbiota reveals novel taxa and extensive sporulation. Nature 533, 543–546 (2016).
Forster, S. C. et al. A human gut bacterial genome and culture collection for improved metagenomic analyses. Nat. Biotechnol. 37, 186–192 (2019).
Otsuji, N., Sekiguchi, M., Iijima, T. & Takagi, Y. Induction of phage formation in the lysogenic Escherichia coli K-12 by mitomycin C. Nature 184, 1079–1080 (1959).
Łoś, J. M., Łoś, M., Wȩgrzyn, A. & Wȩgrzyn, G. Hydrogen peroxide-mediated induction of the Shiga toxin-converting lambdoid prophage ST2-8624 in Escherichia coli O157:H7. FEMS Immunol. Med. Microbiol. 58, 322–329 (2010).
Oh, J.-H. et al. Dietary fructose and microbiota-derived short-chain fatty acids promote bacteriophage production in the gut symbiont Lactobacillus reuteri. Cell Host Microbe 25, 273–284 (2019).
Morris, R. M., Cain, K. R., Hvorecny, K. L. & Kollman, J. M. Lysogenic host–virus interactions in SAR11 marine bacteria. Nat. Microbiol. 5, 1011–1015 (2020).
Boling, L. et al. Dietary prophage inducers and antimicrobials: toward landscaping the human gut microbiome. Gut Microbes 11, 721–734 (2020).
Roux, S. et al. Minimum information about an uncultivated virus genome (MIUVIG). Nat. Biotechnol. 37, 29–37 (2019).
Lopez, J. A. et al. Abundance measurements reveal the balance between lysis and lysogeny in the human gut microbiome. Preprint at bioRxiv https://doi.org/10.1101/2024.09.27.614587 (2024).
Sutcliffe, S. G., Reyes, A. & Maurice, C. F. Bacteriophages playing nice: lysogenic bacteriophage replication stable in the human gut microbiota. iScience 26, 106007 (2023).
Shalon, D. et al. Profiling the human intestinal environment under physiological conditions. Nature 617, 581–591 (2023).
Adriaenssens, E. M. Phage diversity in the human gut microbiome: a taxonomist’s perspective. mSystems 6, e0079921 (2021).
Bin Jang, H. et al. Taxonomic assignment of uncultivated prokaryotic virus genomes is enabled by gene-sharing networks. Nat. Biotechnol. 37, 632–639 (2019).
Benler, S. et al. A diversity-generating retroelement encoded by a globally ubiquitous Bacteroides phage. Microbiome 6, 191 (2018).
Yutin, N. et al. Analysis of metagenome-assembled viral genomes from the human gut reveals diverse putative CrAss-like phages with unique genomic features. Nat. Commun. 12, 1044 (2021).
Reyes, A. et al. Viruses in the faecal microbiota of monozygotic twins and their mothers. Nature 466, 334–338 (2010).
Shkoporov, A. N. et al. The human gut virome is highly diverse, stable, and individual specific. Cell Host Microbe 26, 527–541 (2019).
Liu, M. et al. Reverse transcriptase-mediated tropism switching in Bordetella bacteriophage. Science 295, 2091–2094 (2002).
Roux, S. et al. Ecology and molecular targets of hypermutation in the global microbiome. Nat. Commun. 12, 3076 (2021).
Laurenceau, R. et al. Harnessing diversity generating retroelements for in vivo targeted hyper-mutagenesis. Preprint at bioRxiv https://doi.org/10.1101/2025.03.24.644984 (2025).
Doré, H. et al. Targeted hypermutation of putative antigen sensors in multicellular bacteria. Proc. Natl Acad. Sci. USA 121, e2316469121 (2024).
Terzian, P. et al. PHROG: families of prokaryotic virus proteins clustered using remote homology. NAR Genom. Bioinform. 3, lqab067 (2021).
O’Brien, S., Kümmerli, R., Paterson, S., Winstanley, C. & Brockhurst, M. A. Transposable temperate phages promote the evolution of divergent social strategies in Pseudomonas aeruginosa populations. Proc. R. Soc. B 286, 20191794 (2019).
Moreno-Gallego, J. L. et al. Virome diversity correlates with intestinal microbiome diversity in adult monozygotic twins. Cell Host Microbe 25, 261–272 (2019).
Silpe, J. E., Duddy, O. P. & Bassler, B. L. Induction mechanisms and strategies underlying interprophage competition during polylysogeny. PLoS Pathog. 19, e1011363 (2023).
Refardt, D. Within-host competition determines reproductive success of temperate bacteriophages. ISME J. 5, 1451–1460 (2011).
Azulay, G. et al. A dual-function phage regulator controls the response of cohabiting phage elements via regulation of the bacterial SOS response. Cell Rep. 39, 110723 (2022).
Guo, Y. et al. Control of lysogeny and antiphage defense by a prophage-encoded kinase-phosphatase module. Nat. Commun. 15, 7244 (2024).
Song, S. et al. CRISPR-Cas controls cryptic prophages. Int. J. Mol. Sci. 23, 16195 (2022).
Edgar, R. & Qimron, U. The Escherichia coli CRISPR system protects from λ lysogenization, lysogens, and prophage induction. J. Bacteriol. 192, 6291–6294 (2010).
Silpe, J. E. & Bassler, B. L. A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision. Cell 176, 268–280 (2019).
Silpe, J. E. et al. Small protein modules dictate prophage fates during polylysogeny. Nature 620, 625–633 (2023).
Mathieu, A. et al. Virulent coliphages in 1-year-old children fecal samples are fewer, but more infectious than temperate coliphages. Nat. Commun. 11, 378 (2020).
Lemire, S., Figueroa-Bossi, N. & Bossi, L. Bacteriophage crosstalk: coordination of prophage induction by trans-acting antirepressors. PLoS Genet. 7, e1002149 (2011).
D’Adamo, G. L. et al. Bacterial clade-specific analysis identifies distinct epithelial responses in inflammatory bowel disease. Cell Rep. Med. 4, 101124 (2023).
Stewart, C. S., Hold, G. L., Duncan, S. H., Flint, H. J. & Harmsen, H. J. M. Growth requirements and fermentation products of Fusobacterium prausnitzii, and a proposal to reclassify it as Faecalibacterium prausnitzii gen. nov., comb. nov. Int. J. Syst. Evol. Microbiol. 52, 2141–2146 (2002).
Mende, D. R. et al. ProGenomes: a resource for consistent functional and taxonomic annotations of prokaryotic genomes. Nucleic Acids Res. 45, D529–D534 (2017).
Shen, W., Le, S., Li, Y. & Hu, F. SeqKit: a cross-platform and ultrafast toolkit for FASTA/Q file manipulation. PLoS ONE 11, e0163962 (2016).
Katoh, K. & Standley, D. M. MAFFT multiple sequence alignment software version 7: Improvements in performance and usability. Mol. Biol. Evol. 30, 772–780 (2013).
Capella-Gutiérrez, S., Silla-Martínez, J. M. & Gabaldón, T. trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses. Bioinformatics 25, 1972–1973 (2009).
Stamatakis, A. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics 30, 1312–1313 (2014).
Letunic, I. & Bork, P. Interactive tree of life (iTOL) v5: an online tool for phylogenetic tree display and annotation. Nucleic Acids Res. 49, W293–W296 (2021).
Olm, M. R., Brown, C. T., Brooks, B. & Banfield, J. F. DRep: a tool for fast and accurate genomic comparisons that enables improved genome recovery from metagenomes through de-replication. ISME J. 11, 2864–2868 (2017).
Roux, S., Enault, F., Hurwitz, B. L. & Sullivan, M. B. VirSorter: mining viral signal from microbial genomic data. PeerJ 3, e985 (2015).
Kieft, K., Zhou, Z. & Anantharaman, K. VIBRANT: automated recovery, annotation and curation of microbial viruses, and evaluation of viral community function from genomic sequences. Microbiome 8, 90 (2020).
Ren, J., Ahlgren, N. A., Lu, Y. Y., Fuhrman, J. A. & Sun, F. VirFinder: a novel k-mer based tool for identifying viral sequences from assembled metagenomic data. Microbiome 5, 69 (2017).
Nayfach, S. et al. CheckV assesses the quality and completeness of metagenome-assembled viral genomes. Nat. Biotechnol. 39, 578–585 (2021).
Lawrence, M. et al. Software for computing and annotating genomic ranges. PLoS Comput. Biol. 9, e1003118 (2013).
Alexeeva, S., Guerra Martínez, J. A., Spus, M. & Smid, E. J. Spontaneously induced prophages are abundant in a naturally evolved bacterial starter culture and deliver competitive advantage to the host. BMC Microbiol. 18, 120 (2018).
Chantret, I. et al. Differential expression of sucrase-isomaltase in clones isolated from early and late passages of the cell line caco-2: evidence for glucose-dependent negative regulation. J. Cell Sci. 107, 213–225 (1994).
Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114–2120 (2014).
Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012).
Li, H. et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078–2079 (2009).
Quinlan, A. R. & Hall, I. M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841–842 (2010).
Kieft, K. & Anantharaman, K. Deciphering active prophages from metagenomes. mSystems 7, e00084-22 (2022).
Turkington, C. J. R., Abadi, N. N., Edwards, R. A. & Grasis, J. A. hafeZ: active prophage identification through read mapping. Preprint at bioRxiv https://doi.org/10.1101/2021.07.21.453177 (2021).
Antipov, D., Raiko, M., Lapidus, A. & Pevzner, P. A. Metaviral SPAdes: assembly of viruses from metagenomic data. Bioinformatics 36, 4126–4129 (2020).
Seemann, T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 30, 2068–2069 (2014).
Tisza, M. J., Belford, A. K., Dominguez-Huerta, G., Bolduc, B. & Buck, C. B. Cenote-Taker 2 democratizes virus discovery and sequence annotation. Virus Evol. 7, veaa100 (2021).
Eddy, S. R. Accelerated profile HMM searches. PLoS Comp. Biol. 7, e1002195 (2011).
Cook, R. et al. INfrastructure for a PHAge REference Database: identification of large-scale biases in the current collection of cultured phage genomes. Phage 2, 214–223 (2021).
Wang, H. et al. Gut virome of mammals and birds reveals high genetic diversity of the family Microviridae. Virus Evol. 5, vez013 (2019).
Ibrahim, B. et al. Bioinformatics meets virology: the European Virus Bioinformatics Center’s second annual meeting. Viruses 10, 256 (2018).
Yutin, N., Bäckström, D., Ettema, T. J. G., Krupovic, M. & Koonin, E. V. Vast diversity of prokaryotic virus genomes encoding double jelly-roll major capsid proteins uncovered by genomic and metagenomic sequence analysis. Virol. J. 15, 67 (2018).
Roux, S., Krupovic, M., Daly, R.A. et al. Cryptic inoviruses revealed as pervasive in bacteria and archaea across Earth’s biomes. Nat. Microbiol. 4, 1895–1906 (2019).
Breitwieser, F. P., Baker, D. N. & Salzberg, S. L. KrakenUniq: confident and fast metagenomics classification using unique k-mer counts. Genome Biol. 19, 198 (2018).
Ondov, B. D. et al. Mash: fast genome and metagenome distance estimation using MinHash. Genome Biol. 17, 132 (2016).
Simonsen, M., Mailund, T. & Pedersen, C. N. S. in Algorithms in Bioinformatics (eds Crandall, K. A. & Lagergren, J.) 113–122 (Springer, 2008).
Solari, S. M., Young, R. B., Marcelino, V. R. & Forster, S. C. Expam—high-resolution analysis of metagenomes using distance trees. Bioinformatics 38, 4814–4816 (2022).
Ye, Y. Identification of diversity-generating retroelements in human microbiomes. Int. J. Mol. Sci. 15, 14234–14246 (2014).
Cobián Güemes, A. G. et al. Viruses as winners in the game of life. Annu. Rev. Virol. 3, 197–214 (2016).
O’Donnell, S. & Fischer, G. MUM&Co: accurate detection of all SV types through whole-genome alignment. Bioinformatics 36, 3242–3243 (2020).
Jain, C., Rodriguez-R, L. M., Phillippy, A. M., Konstantinidis, K. T. & Aluru, S. High throughput ANI analysis of 90 K prokaryotic genomes reveals clear species boundaries. Nat. Commun. 9, 5114 (2018).
Olm, M. R. et al. Consistent metagenome-derived metrics verify and delineate bacterial species boundaries. mSystems 5, e00731-19 (2020).
Zheng, L. et al. CRISPR/Cas-based genome editing for human gut commensal Bacteroides species. ACS Synth. Biol. 11, 464–472 (2022).
Wick, R. R., Judd, L. M., Gorrie, C. L. & Holt, K. E. Unicycler: resolving bacterial genome assemblies from short and long sequencing reads. PLoS Comput. Biol. 13, e1005595 (2017).
Alonge, M. et al. Automated assembly scaffolding using RagTag elevates a new tomato system for high-throughput genome editing. Genome Biol. 23, 258 (2022).
Dahlman, S. et al. Data and code for ‘Isolation, engineering and ecological dynamics of temperate phages from the human gut’. Figshare https://doi.org/10.26180/29946902.v1 (2025).