Ménage à trois in the human gut: interactions between host, bacteria and phages (original) (raw)

• Rohwer, F., Prangishvili, D. & Lindell, D. Roles of viruses in the environment. Environ. Microbiol. 11, 2771–2774 (2009).
  Article PubMed Google Scholar
• Mills, S. et al. Movers and shakers: influence of bacteriophages in shaping the mammalian gut microbiota. Gut Microbes 4, 4–16 (2013).
  Article PubMed PubMed Central Google Scholar
• De Smet, J. et al. High coverage metabolomics analysis reveals phage-specific alterations to Pseudomonas aeruginosa physiology during infection. ISME J. 10, 1823–1835 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Rodriguez-Valera, F. et al. Explaining microbial population genomics through phage predation. Nat. Rev. Microbiol. 7, 828–836 (2009).
  Article CAS PubMed Google Scholar
• Enault, F. et al. Phages rarely encode antibiotic resistance genes: a cautionary tale for virome analyses. ISME J. 11, 237–247 (2017).
  Article CAS PubMed Google Scholar
• Parfrey, L. W., Walters, W. A. & Knight, R. Microbial eukaryotes in the human microbiome: ecology, evolution, and future directions. Front. Microbiol. 2, 153 (2011).
  Article PubMed PubMed Central Google Scholar
• Hoffmann, C. et al. Archaea and fungi of the human gut microbiome: correlations with diet and bacterial residents. PLoS ONE 8, e66019 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 486, 207–214 (2012).
• Hewitson, J. P. & Maizels, R. M. Vaccination against helminth parasite infections. Expert Rev. Vaccines 13, 473–487 (2014).
  Article CAS PubMed Google Scholar
• Tlaskalova-Hogenova, H. et al. The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases. Cell. Mol. Immunol. 8, 110–120 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Wilson, M. in Bacteriology of Humans: An Ecological Perspective 278–279 (Wiley-Blackwell, 2008).
  Google Scholar
• Blaut, M. Ecology and physiology of the intestinal tract. Curr. Top. Microbiol. Immunol. 358, 247–272 (2013).
  PubMed Google Scholar
• Cotillard, A. et al. Dietary intervention impact on gut microbial gene richness. Nature 500, 585–588 (2013).
  Article CAS PubMed Google Scholar
• Kamada, N., Seo, S. U., Chen, G. Y. & Nunez, G. Role of the gut microbiota in immunity and inflammatory disease. Nat. Rev. Immunol. 13, 321–335 (2013).
  Article CAS PubMed Google Scholar
• Eckburg, P. B. et al. Diversity of the human intestinal microbial flora. Science 308, 1635–1638 (2005).
  Article PubMed PubMed Central Google Scholar
• Sommer, F. & Backhed, F. The gut microbiota — masters of host development and physiology. Nat. Rev. Microbiol. 11, 227–238 (2013).
  Article CAS PubMed Google Scholar
• Ley, R. E., Peterson, D. A. & Gordon, J. I. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 124, 837–848 (2006). A review that identifies possible ecological rules governing the diversity of the bacterial communities in the human gut.
  Article CAS PubMed Google Scholar
• Faith, J. J. et al. The long-term stability of the human gut microbiota. Science 341, 1237439 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Turnbaugh, P. J. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027–1031 (2006).
  Article PubMed Google Scholar
• Frank, D. N. et al. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc. Natl Acad. Sci. USA 104, 13780–13785 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Qin, J. et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490, 55–60 (2012).
  Article CAS PubMed Google Scholar
• David, L. A. et al. Host lifestyle affects human microbiota on daily timescales. Genome Biol. 15, R89 (2014). This study provides a comprehensive time-series analysis of gut and oral bacterial communities in two healthy individuals over the course of 1 year.
  Article CAS PubMed PubMed Central Google Scholar
• Ley, R. E. et al. Evolution of mammals and their gut microbes. Science 320, 1647–1651 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Lozupone, C. A., Stombaugh, J. I., Gordon, J. I., Jansson, J. K. & Knight, R. Diversity, stability and resilience of the human gut microbiota. Nature 489, 220–230 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• David, L. A. et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559–563 (2014).
  Article CAS PubMed Google Scholar
• Breitbart, M. et al. Metagenomic analyses of an uncultured viral community from human feces. J. Bacteriol. 185, 6220–6223 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Minot, S. et al. The human gut virome: inter-individual variation and dynamic response to diet. Genome Res. 21, 1616–1625 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Norman, J. M. et al. Disease-specific alterations in the enteric virome in inflammatory bowel disease. Cell 160, 447–460 (2015). This study details a comparison between the gut viromes of patients with IBD, showing disease-specific changes in virome diversity that are not explained by the changes in bacterial communities.
  Article CAS PubMed PubMed Central Google Scholar
• Reyes, A. et al. Gut DNA viromes of Malawian twins discordant for severe acute malnutrition. Proc. Natl Acad. Sci. USA 112, 11941–11946 (2015).
  Article CAS PubMed PubMed Central Google Scholar
• Reyes, A. et al. Viruses in the faecal microbiota of monozygotic twins and their mothers. Nature 466, 334–338 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Reyes, A., Wu, M., McNulty, N. P., Rohwer, F. L. & Gordon, J. I. Gnotobiotic mouse model of phage–bacterial host dynamics in the human gut. Proc. Natl Acad. Sci. USA 110, 20236–20241 (2013). This study shows that mice that are colonized by a specific bacterial community isolated from the human gut and are infected by phages have reproducible and non-simultaneous bacterial infection patterns.
  Article CAS PubMed PubMed Central Google Scholar
• Zhang, T. et al. RNA viral community in human feces: prevalence of plant pathogenic viruses. PLoS Biol. 4, e3 (2006).
  Article CAS PubMed Google Scholar
• Minot, S. et al. Rapid evolution of the human gut virome. Proc. Natl Acad. Sci. USA 110, 12450–12455 (2013). A temporal study of the healthy human gut virome over 2.5 years, which shows long-term stability of diversity in the gut virome and the rapid evolution of some long-term members of the gut virome.
  Article CAS PubMed PubMed Central Google Scholar
• Manrique, P. et al. Healthy human gut phageome. Proc. Natl Acad. Sci. USA 113, 10400–10405 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Browne, H. P. et al. Culturing of 'unculturable' human microbiota reveals novel taxa and extensive sporulation. Nature 533, 543–546 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Myhrvold, C., Kotula, J. W., Hicks, W. M., Conway, N. J. & Silver, P. A. A distributed cell division counter reveals growth dynamics in the gut microbiota. Nat. Commun. 6, 10039 (2015).
  Article CAS PubMed Google Scholar
• Breitbart, M. et al. Viral diversity and dynamics in an infant gut. Res. Microbiol. 159, 367–373 (2008).
  Article CAS PubMed Google Scholar
• Sharon, I. et al. Time series community genomics analysis reveals rapid shifts in bacterial species, strains, and phage during infant gut colonization. Genome Res. 23, 111–120 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Koenig, J. E. et al. Succession of microbial consortia in the developing infant gut microbiome. Proc. Natl Acad. Sci. USA 108 (Suppl. 1), 4578–4585 (2011).
  Article CAS PubMed Google Scholar
• Lim, E. S. et al. Early life dynamics of the human gut virome and bacterial microbiome in infants. Nat. Med. 21, 1228–1234 (2015).
  Article CAS PubMed PubMed Central Google Scholar
• Dominguez-Bello, M. G. et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc. Natl Acad. Sci. USA 107, 11971–11975 (2010).
  Article PubMed PubMed Central Google Scholar
• Thingstad, T. F. Elements of a theory for the mechanisms controlling abundance, diversity, and biogeochemical role of lytic bacterial viruses in aquatic systems. Limnol. Oceanogr. 45, 1320–1328 (2000).
  Article Google Scholar
• Weinbauer, M. G. & Rassoulzadegan, F. Are viruses driving microbial diversification and diversity? Environ. Microbiol. 6, 1–11 (2004).
  Article PubMed Google Scholar
• Mahana, D. et al. Antibiotic perturbation of the murine gut microbiome enhances the adiposity, insulin resistance, and liver disease associated with high-fat diet. Genome Med. 8, 48 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Charbonneau, M. R. et al. Sialylated milk oligosaccharides promote microbiota-dependent growth in models of infant undernutrition. Cell 164, 859–871 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Harrison, E., Laine, A. L., Hietala, M. & Brockhurst, M. A. Rapidly fluctuating environments constrain coevolutionary arms races by impeding selective sweeps. Proc. Biol. Sci. 280, 20130937 (2013).
  Article PubMed PubMed Central Google Scholar
• Gomez, P. & Buckling, A. Bacteria–phage antagonistic coevolution in soil. Science 332, 106–109 (2011). This study in soil microcosms illustrates that bacteria–phage coevolution in soil leads to fluctuating selection dynamics between bacteria and phages.
  Article CAS PubMed Google Scholar
• Hall, A. R., Scanlan, P. D., Morgan, A. D. & Buckling, A. Host–parasite coevolutionary arms races give way to fluctuating selection. Ecol. Lett. 14, 635–642 (2011).
  Article PubMed Google Scholar
• van Houte, S., Buckling, A. & Westra, E. R. Evolutionary ecology of prokaryotic immune mechanisms. Microbiol. Mol. Biol. Rev. 80, 745–763 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Lopez Pascua, L. et al. Higher resources decrease fluctuating selection during host–parasite coevolution. Ecol. Lett. 17, 1380–1388 (2014).
  Article PubMed PubMed Central Google Scholar
• Williamson, K. E., Radosevich, M., Smith, D. W. & Wommack, K. E. Incidence of lysogeny within temperate and extreme soil environments. Environ. Microbiol. 9, 2563–2574 (2007).
  Article CAS PubMed Google Scholar
• Weinbauer, M. G., Brettar, I. & Hofle, M. G. Lysogeny and virus-induced mortality of bacterioplankton in surface, deep, and anoxic marine waters. Limnol. Oceanogr. 48, 1457–1465 (2003).
  Article Google Scholar
• Weinbauer, M. G. Ecology of prokaryotic viruses. FEMS Microbiol. Rev. 28, 127–181 (2004).
  Article CAS PubMed Google Scholar
• Silveira, C. B. & Rohwer, F. L. Piggyback-the-Winner in host-associated microbial communities. NPJ Biofilms Microbiomes 2, 16010 (2016).
  Article PubMed PubMed Central Google Scholar
• Lenski, R. E. Dynamics of interactions between bacteria and virulent bacteriophage. Adv. Microb. Ecol. 10, 1–44 (1988).
  Article CAS Google Scholar
• Knowles, B. et al. Lytic to temperate switching of viral communities. Nature 531, 466–470 (2016). This study proposes the piggyback-the-winner model in host-associated microbial communities.
  Article CAS PubMed Google Scholar
• Touchon, M., Bernheim, A. & Rocha, E. P. Genetic and life-history traits associated with the distribution of prophages in bacteria. ISME J. 10, 2744–2754 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Peterson, D. A., Frank, D. N., Pace, N. R. & Gordon, J. I. Metagenomic approaches for defining the pathogenesis of inflammatory bowel diseases. Cell Host Microbe 3, 417–427 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Perez-Brocal, V. et al. Study of the viral and microbial communities associated with Crohn's disease: a metagenomic approach. Clin. Transl Gastroenterol. 4, e36 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Lepage, P. et al. Dysbiosis in inflammatory bowel disease: a role for bacteriophages? Gut 57, 424–425 (2008).
  Article CAS PubMed Google Scholar
• Brockhurst, M. A., Morgan, A. D., Fenton, A. & Buckling, A. Experimental coevolution with bacteria and phage. The _Pseudomonas fluorescens–_Φ2 model system. Infect. Genet. Evol. 7, 547–552 (2007).
  Article CAS PubMed Google Scholar
• Maranger, R. & Bird, D. F. Viral abundance in aquatic systems — a comparison between marine and fresh-waters. Mar. Ecol. Prog. Ser. 121, 217–226 (1995).
  Article Google Scholar
• Williamson, K. E., Radosevich, M. & Wommack, K. E. Abundance and diversity of viruses in six Delaware soils. Appl. Environ. Microbiol. 71, 3119–3125 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Hodyra-Stefaniak, K. et al. Mammalian host-versus-phage immune response determines phage fate in vivo. Sci. Rep. 5, 14802 (2015).
  Article CAS PubMed PubMed Central Google Scholar
• Majewska, J. et al. Oral application of T4 phage induces weak antibody production in the gut and in the blood. Viruses 7, 4783–4799 (2015).
  Article CAS PubMed PubMed Central Google Scholar
• Dabrowska, K. et al. Immunogenicity studies of proteins forming the T4 phage head surface. J. Virol. 88, 12551–12557 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Miernikiewicz, P. et al. T4 phage tail adhesin Gp12 counteracts LPS-induced inflammation in vivo. Front. Microbiol. 7, 1112 (2016).
  Article PubMed PubMed Central Google Scholar
• Barr, J. J. et al. Bacteriophage adhering to mucus provide a non-host-derived immunity. Proc. Natl Acad. Sci. USA 110, 10771–10776 (2013). This study shows that phage immunoglobulin-like proteins enable increased phage adherence to mucosal surfaces of metazoan hosts, including human intestinal cells, and provide a first line of defence against bacterial pathogens.
  Article CAS PubMed PubMed Central Google Scholar
• Mogensen, T. H. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin. Microbiol. Rev. 22, 240–273 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Fischbach, M. A. & Sonnenburg, J. L. Eating for two: how metabolism establishes interspecies interactions in the gut. Cell Host Microbe 10, 336–347 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Rossmann, F. S. et al. Phage-mediated dispersal of biofilm and distribution of bacterial virulence genes is induced by quorum sensing. PLoS Pathog. 11, e1004653 (2015).
  Article CAS PubMed PubMed Central Google Scholar
• Erez, Z. et al. Communication between viruses guides lysis–lysogeny decisions. Nature 541, 488–493 (2017). This study characterizes three phage genes that are involved in a phage-specific peptide communication system to coordinate the lysis–lysogeny decision of phages from the SPbeta group.
  Article CAS PubMed PubMed Central Google Scholar
• Jonczyk, E., Klak, M., Miedzybrodzki, R. & Gorski, A. The influence of external factors on bacteriophages — review. Folia Microbiol. (Praha) 56, 191–200 (2011).
  Article CAS Google Scholar
• Verthe, K., Possemiers, S., Boon, N., Vaneechoutte, M. & Verstraete, W. Stability and activity of an _Enterobacter aerogenes_-specific bacteriophage under simulated gastro-intestinal conditions. Appl. Microbiol. Biotechnol. 65, 465–472 (2004).
  Article CAS PubMed Google Scholar
• Ma, Y. et al. Microencapsulation of bacteriophage felix O1 into chitosan-alginate microspheres for oral delivery. Appl. Environ. Microbiol. 74, 4799–4805 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Maura, D., Galtier, M., Le Bouguenec, C. & Debarbieux, L. Virulent bacteriophages can target O104:H4 enteroaggregative Escherichia coli in the mouse intestine. Antimicrob. Agents Chemother. 56, 6235–6242 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Turnbaugh, P. J., Backhed, F., Fulton, L. & Gordon, J. I. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe 3, 213–223 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Kim, M. S. & Bae, J. W. Spatial disturbances in altered mucosal and luminal gut viromes of diet-induced obese mice. Environ. Microbiol. 18, 1498–1510 (2016).
  Article CAS PubMed Google Scholar
• United Nations Children's Fund, World Health Organization & The World Bank. UNICEF–WHO–World Bank joint child malnutrition estimates. World Health Organization http://www.who.int/nutgrowthdb/jme_unicef_who_wb.pdf (2012).
• Subramanian, S. et al. Persistent gut microbiota immaturity in malnourished Bangladeshi children. Nature 510, 417–421 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Maurice, C. F., Haiser, H. J. & Turnbaugh, P. J. Xenobiotics shape the physiology and gene expression of the active human gut microbiome. Cell 152, 39–50 (2013). This in vitro study identifies the rapid effects of therapeutic compounds on the gene expression, physiology and community structure of healthy gut bacterial communities, including the higher transcription of prophage induction genes.
  Article CAS PubMed PubMed Central Google Scholar
• Pavlova, S. I. & Tao, L. Induction of vaginal Lactobacillus phages by the cigarette smoke chemical benzo[_a_]pyrene diol epoxide. Mutat. Res. 466, 57–62 (2000).
  Article CAS PubMed Google Scholar
• Willner, D. et al. Metagenomic detection of phage-encoded platelet-binding factors in the human oral cavity. Proc. Natl Acad. Sci. USA 108 (Suppl. 1), 4547–4553 (2011).
  Article CAS PubMed Google Scholar
• Taguer, M. & Maurice, C. F. The complex interplay of diet, xenobiotics, and microbial metabolism in the gut: implications for clinical outcomes. Clin. Pharmacol. Ther. 99, 588–599 (2016).
  Article CAS PubMed Google Scholar
• Mylon, S. E. et al. Influence of salts and natural organic matter on the stability of bacteriophage MS2. Langmuir 26, 1035–1042 (2010).
  Article CAS PubMed Google Scholar
• Lenzi, L. J., Lucchesi, P. M., Medico, L., Burgan, J. & Kruger, A. Effect of the food additives sodium citrate and disodium phosphate on shiga toxin-producing Escherichia coli and production of stx-phages and Shiga toxin. Front. Microbiol. 7, 992 (2016).
  Article PubMed PubMed Central Google Scholar
• Allen, H. K. et al. Antibiotics in feed induce prophages in swine fecal microbiomes. mBio 2, e00260-11 (2011).
  Article PubMed PubMed Central Google Scholar
• DeMarini, D. M. & Lawrence, B. K. Prophage induction by DNA topoisomerase II poisons and reactive-oxygen species: role of DNA breaks. Mutat. Res. 267, 1–17 (1992).
  Article CAS PubMed Google Scholar
• Wegrzyn, G. & Wegrzyn, A. Genetic switches during bacteriophage λ development. Prog. Nucleic Acid Res. Mol. Biol. 79, 1–48 (2005).
  Article CAS PubMed Google Scholar
• Modi, S. R., Lee, H. H., Spina, C. S. & Collins, J. J. Antibiotic treatment expands the resistance reservoir and ecological network of the phage metagenome. Nature 499, 219–222 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Los, J. M., Los, M., Wegrzyn, G. & Wegrzyn, A. Differential efficiency of induction of various lambdoid prophages responsible for production of Shiga toxins in response to different induction agents. Microb. Pathog. 47, 289–298 (2009).
  Article CAS PubMed Google Scholar
• Volkova, V. V., Lu, Z., Besser, T. & Grohn, Y. T. Modeling the infection dynamics of bacteriophages in enteric Escherichia coli: estimating the contribution of transduction to antimicrobial gene spread. Appl. Environ. Microbiol. 80, 4350–4362 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Sarker, S. A. et al. Oral phage therapy of acute bacterial diarrhea with two coliphage preparations: a randomized trial in children from Bangladesh. EBioMedicine 4, 124–137 (2016).
  Article PubMed PubMed Central Google Scholar
• Nailor, M. D. & Sobel, J. D. Antibiotics for Gram-positive bacterial infections: vancomycin, teicoplanin, quinupristin/dalfopristin, oxazolidinones, daptomycin, dalbavancin, and telavancin. Infect. Dis. Clin. North Am. 23, 965–982 (2009).
  Article PubMed Google Scholar
• Ross, A., Ward, S. & Hyman, P. More is better: selecting for broad host range bacteriophages. Front. Microbiol. 7, 1352 (2016).
  Article PubMed PubMed Central Google Scholar
• Bruttin, A. & Brussow, H. Human volunteers receiving Escherichia coli phage T4 orally: a safety test of phage therapy. Antimicrob. Agents Chemother. 49, 2874–2878 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Galtier, M. et al. Bacteriophages to reduce gut carriage of antibiotic resistant uropathogens with low impact on microbiota composition. Environ. Microbiol. 18, 2237–2245 (2016).
  Article CAS PubMed Google Scholar
• Wright, A., Hawkins, C. H., Anggard, E. E. & Harper, D. R. A controlled clinical trial of a therapeutic bacteriophage preparation in chronic otitis due to antibiotic-resistant Pseudomonas aeruginosa; a preliminary report of efficacy. Clin. Otolaryngol. 34, 349–357 (2009).
  Article CAS PubMed Google Scholar
• US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02116010 (2015).
• US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02664740 (2016).
• Lu, T. K. & Collins, J. J. Engineered bacteriophage targeting gene networks as adjuvants for antibiotic therapy. Proc. Natl Acad. Sci. USA 106, 4629–4634 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Libis, V. K. et al. Silencing of antibiotic resistance in E. coli with engineered phage bearing small regulatory RNAs. ACS Synth. Biol. 3, 1003–1006 (2014).
  Article CAS PubMed Google Scholar
• Chan, B. K. et al. Phage selection restores antibiotic sensitivity in MDR Pseudomonas aeruginosa. Sci. Rep. 6, 26717 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Alang, N. & Kelly, C. R. Weight gain after fecal microbiota transplantation. Open Forum Infect. Dis. 2, ofv004 (2015).
  Article PubMed PubMed Central Google Scholar
• Sheth, R. U., Cabral, V., Chen, S. P. & Wang, H. H. Manipulating bacterial communities by in situ microbiome engineering. Trends Genet. 32, 189–200 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Cooper, C., Khan Mirzaei, M. & Nilsson, A. S. Adapting drug approval pathways for bacteriophage-based therapeutics. Front. Microbiol. 7, 1209 (2016).
  PubMed PubMed Central Google Scholar
• Nale, J. Y. et al. Bacteriophage combinations significantly reduce Clostridium difficile growth in vitro and proliferation in vivo. Antimicrob. Agents Chemother. 60, 968–981 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Abedon, S. T., Kuhl, S. J., Blasdel, B. G. & Kutter, E. M. Phage treatment of human infections. Bacteriophage 1, 66–85 (2011). A review of historical and contemporary research on the use of phages to treat human infections.
  Article PubMed PubMed Central Google Scholar
• Manichanh, C., Borruel, N., Casellas, F. & Guarner, F. The gut microbiota in IBD. Nat. Rev. Gastroenterol. Hepatol. 9, 599–608 (2012).
  Article CAS PubMed Google Scholar
• Pirnay, J. P. et al. The phage therapy paradigm: pret-a-porter or sur-mesure? Pharm. Res. 28, 934–937 (2011).
  Article CAS PubMed Google Scholar
• Nilsson, A. S. Phage therapy — constraints and possibilities. Ups. J. Med. Sci. 119, 192–198 (2014).
  Article PubMed PubMed Central Google Scholar
• Swidsinski, A., Weber, J., Loening-Baucke, V., Hale, L. P. & Lochs, H. Spatial organization and composition of the mucosal flora in patients with inflammatory bowel disease. J. Clin. Microbiol. 43, 3380–3389 (2005).
  Article PubMed PubMed Central Google Scholar
• Bull, J. J. & Gill, J. J. The habits of highly effective phages: population dynamics as a framework for identifying therapeutic phages. Front. Microbiol. 5, 618 (2014).
  Article PubMed PubMed Central Google Scholar
• Khan Mirzaei, M. & Nilsson, A. S. Isolation of phages for phage therapy: a comparison of spot tests and efficiency of plating analyses for determination of host range and efficacy. PLoS ONE 10, e0118557 (2015).
  Article CAS PubMed PubMed Central Google Scholar
• Dutilh, B. E. et al. A highly abundant bacteriophage discovered in the unknown sequences of human faecal metagenomes. Nat. Commun. 5, 4498 (2014).
  Article CAS PubMed Google Scholar
• Ley, R. E. et al. Obesity alters gut microbial ecology. Proc. Natl Acad. Sci. USA 102, 11070–11075 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Paul, J. H. Prophages in marine bacteria: dangerous molecular time bombs or the key to survival in the seas? ISME J. 2, 579–589 (2008). This study identifies phage-encoded repressors and transcriptional regulators of bacterial metabolism that enable the survival of the bacterial host in unfavourable environmental conditions in marine systems.
  Article CAS PubMed Google Scholar
• Brussow, H., Canchaya, C. & Hardt, W. D. Phages and the evolution of bacterial pathogens: from genomic rearrangements to lysogenic conversion. Microbiol. Mol. Biol. Rev. 68, 560–602 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Smeal, S. W., Schmitt, M. A., Pereira, R. R., Prasad, A. & Fisk, J. D. Simulation of the M13 life cycle I: assembly of a genetically-structured deterministic chemical kinetic simulation. Virology 500, 259–274 (2017).
  Article CAS PubMed Google Scholar
• Cenens, W., Makumi, A., Mebrhatu, M. T., Lavigne, R. & Aertsen, A. Phage–host interactions during pseudolysogeny: lessons from the Pid/dgo interaction. Bacteriophage 3, e25029 (2013).
  Article PubMed PubMed Central Google Scholar
• Feiner, R. et al. A new perspective on lysogeny: prophages as active regulatory switches of bacteria. Nat. Rev. Microbiol. 13, 641–650 (2015).
  Article CAS PubMed Google Scholar
• Reyesa, A. et al. Gut DNA viromes of Malawian twins discordant for severe acute malnutrition. Proc. Natl Acad. Sci. USA 112, 11941–11946 (2015).
  Article CAS Google Scholar
• Thingstad, T. F. & Lignell, R. Theoretical models for the control of bacterial growth rate, abundance, diversity and carbon demand. Aquat. Microb. Ecol. 13, 19–27 (1997).
  Article Google Scholar
• Maurice, C. F. et al. Disentangling the relative influence of bacterioplankton phylogeny and metabolism on lysogeny in reservoirs and lagoons. ISME J. 5, 831–842 (2011).
  Article CAS PubMed Google Scholar
• Bibby, K. Improved bacteriophage genome data is necessary for integrating viral and bacterial ecology. Microb. Ecol. 67, 242–244 (2014).
  Article PubMed Google Scholar
• Labrie, S. J., Samson, J. E. & Moineau, S. Bacteriophage resistance mechanisms. Nat. Rev. Microbiol. 8, 317–327 (2010).
  Article CAS PubMed Google Scholar
• Samson, J. E., Magadan, A. H., Sabri, M. & Moineau, S. Revenge of the phages: defeating bacterial defences. Nat. Rev. Microbiol. 11, 675–687 (2013).
  Article CAS PubMed Google Scholar
• Stern, A. & Sorek, R. The phage–host arms race: shaping the evolution of microbes. Bioessays 33, 43–51 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Weitz, J. S., Hartman, H. & Levin, S. A. Coevolutionary arms races between bacteria and bacteriophage. Proc. Natl Acad. Sci. USA 102, 9535–9540 (2005).
  Article CAS PubMed PubMed Central Google Scholar