Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Bacteriophages and their potential for treatment of gastrointestinal diseases

Abstract

Although bacteriophages have been overshadowed as therapeutic agents by antibiotics for decades, the emergence of multidrug-resistant bacteria and a better understanding of the role of the gut microbiota in human health and disease have brought them back into focus. In this Perspective, we briefly introduce basic phage biology and summarize recent discoveries about phages in relation to their role in the gut microbiota and gastrointestinal diseases, such as inflammatory bowel disease and chronic liver disease. In addition, we review preclinical studies and clinical trials of phage therapy for enteric disease and explore current challenges and potential future directions.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Fig. 1: Intestinal phageome of healthy individuals and patients with inflammatory bowel disease.
Fig. 2: Manipulation of the gut microbiota by phages.
Fig. 3: Potential applications of phages.

References

  1. 1.

    Ni, J., Wu, G. D., Albenberg, L. & Tomov, V. T. Gut microbiota and IBD: causation or correlation? Nat. Rev. Gastroenterol. Hepatol. 14, 573–584 (2017).

    PubMed  PubMed Central  Google Scholar 

  2. 2.

    Tripathi, A. et al. The gut–liver axis and the intersection with the microbiome. Nat. Rev. Gastroenterol. Hepatol. 15, 397–411 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Wong, S. H. & Yu, J. Gut microbiota in colorectal cancer: mechanisms of action and clinical applications. Nat. Rev. Gastroenterol. Hepatol. 16, 690–704 (2019).

    CAS  PubMed  Google Scholar 

  4. 4.

    Young, V. B. The role of the microbiome in human health and disease: an introduction for clinicians. BMJ 356, j831 (2017).

    PubMed  Google Scholar 

  5. 5.

    Lurie-Weinberger, M. N. & Gophna, U. Archaea in and on the human body: health implications and future directions. PLOS Pathog. 11, e1004833 (2015).

    PubMed  PubMed Central  Google Scholar 

  6. 6.

    Chu, H. et al. The Candida albicans exotoxin candidalysin promotes alcohol-associated liver disease. J. Hepatol. 72, 391–400 (2020).

    CAS  PubMed  Google Scholar 

  7. 7.

    Lang, S. et al. Intestinal fungal dysbiosis and systemic immune response to fungi in patients with alcoholic hepatitis. Hepatology 71, 522–538 (2020).

    CAS  PubMed  Google Scholar 

  8. 8.

    Norman, J. M. et al. Disease-specific alterations in the enteric virome in inflammatory bowel disease. Cell 160, 447–460 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. 9.

    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).

    CAS  PubMed  Google Scholar 

  10. 10.

    Zuo, T. et al. Gut mucosal virome alterations in ulcerative colitis. Gut 68, 1169–1179 (2019).

    CAS  PubMed  Google Scholar 

  11. 11.

    Hannigan, G. D., Duhaime, M. B., Ruffin, M. T., Koumpouras, C. C. & Schloss, P. D. Diagnostic potential and interactive dynamics of the colorectal cancer virome. mBio 9, e02248-18 (2018).

    PubMed  PubMed Central  Google Scholar 

  12. 12.

    Nakatsu, G. et al. Alterations in enteric virome are associated with colorectal cancer and survival outcomes. Gastroenterology 155, 529–541 (2018).

    PubMed  Google Scholar 

  13. 13.

    Jiang, L. et al. Intestinal virome in patients with alcoholic hepatitis. Hepatology 72, 2182–2196 (2020).

    CAS  PubMed  Google Scholar 

  14. 14.

    Lang, S. et al. Intestinal virome signature associated with severity of nonalcoholic fatty liver disease. Gastroenterology 159, 1839–1852 (2020).

    CAS  PubMed  Google Scholar 

  15. 15.

    Shkoporov, A. N. & Hill, C. Bacteriophages of the human gut: the “known unknown” of the microbiome. Cell Host Microbe 25, 195–209 (2019).

    CAS  PubMed  Google Scholar 

  16. 16.

    Twort, F. W. An investigation on the nature of ultra-microscopic viruses. Lancet 186, 1241–1243 (1915).

    Google Scholar 

  17. 17.

    d’Herelle, F. Sur un microbe invisible antagoniste des bacilles dysenteriques [French]. C. R. Acad. Sci. 165, 373–375 (1917).

    Google Scholar 

  18. 18.

    Summers, W. C. Bacteriophage therapy. Annu. Rev. Microbiol. 55, 437–451 (2001).

    CAS  PubMed  Google Scholar 

  19. 19.

    Fleming, A. On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenza. Br. J. Exp. Pathol. 10, 226–236 (1929).

    CAS  PubMed Central  Google Scholar 

  20. 20.

    Aminov, R. History of antimicrobial drug discovery: major classes and health impact. Biochem. Pharmacol. 133, 4–19 (2017).

    CAS  PubMed  Google Scholar 

  21. 21.

    Goossens, H., Ferech, M., Stichele, R. V. & Elseviers, M. Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. Lancet 365, 579–587 (2005).

    PubMed  Google Scholar 

  22. 22.

    Spellberg, B., Bartlett, J. G. & Gilbert, D. N. The future of antibiotics and resistance. N. Engl. J. Med. 368, 299–302 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Becattini, S., Taur, Y. & Pamer, E. G. Antibiotic-induced changes in the intestinal microbiota and disease. Trends Mol. Med. 22, 458–478 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Vila, A. V. et al. Impact of commonly used drugs on the composition and metabolic function of the gut microbiota. Nat. Commun. 11, 362 (2020).

    Google Scholar 

  25. 25.

    Bobay, L. M. & Ochman, H. Biological species in the viral world. Proc. Natl Acad. Sci. USA 115, 6040–6045 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Mushegian, A. R. Are there 1031 virus particles on earth, or more, or fewer? J. Bacteriol. 202, e00052-20 (2020).

    PubMed  PubMed Central  Google Scholar 

  27. 27.

    Rohwer, F. Global phage diversity. Cell 113, 141 (2003).

    CAS  PubMed  Google Scholar 

  28. 28.

    Clokie, M. R. J., Millard, A. D., Letarov, A. V. & Heaphy, S. Phages in nature. Bacteriophage 1, 31–45 (2011).

    PubMed  PubMed Central  Google Scholar 

  29. 29.

    Ashelford, K. E., Day, M. J. & Fry, J. C. Elevated abundance of bacteriophage infecting bacteria in soil. Appl. Environ. Microbiol. 69, 285–289 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Pratama, A. A. & van Elsas, J. D. The ‘neglected’ soil virome–potential role and impact. Trends Microbiol. 26, 649–662 (2018).

    CAS  PubMed  Google Scholar 

  31. 31.

    Suttle, C. A. Viruses in the sea. Nature 437, 356–361 (2005).

    CAS  PubMed  Google Scholar 

  32. 32.

    Suttle, C. A. Marine viruses–major players in the global ecosystem. Nat. Rev. Microbiol. 5, 801–812 (2007).

    CAS  PubMed  Google Scholar 

  33. 33.

    Paez-Espino, D. et al. Uncovering earth’s virome. Nature 536, 425–430 (2016).

    CAS  PubMed  Google Scholar 

  34. 34.

    Manrique, P. et al. Healthy human gut phageome. Proc. Natl Acad. Sci. USA 113, 10400–10405 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Reyes, A. et al. Viruses in the faecal microbiota of monozygotic twins and their mothers. Nature 466, 334–338 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Reyes, A., Semenkovich, N. P., Whiteson, K., Rohwer, F. & Gordon, J. I. Going viral: next-generation sequencing applied to phage populations in the human gut. Nat. Rev. Microbiol. 10, 607–617 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Hendrix, R. W. Bacteriophage genomics. Curr. Opin. Microbiol. 6, 506–511 (2003).

    CAS  PubMed  Google Scholar 

  38. 38.

    Hatfull, G. F. Bacteriophage genomics. Curr. Opin. Microbiol. 11, 447–453 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Ackermann, H. W. & Prangishvili, D. Prokaryote viruses studied by electron microscopy. Arch. Virol. 157, 1843–1849 (2012).

    CAS  PubMed  Google Scholar 

  40. 40.

    Dion, M. B., Oechslin, F. & Moineau, S. Phage diversity, genomics and phylogeny. Nat. Rev. Microbiol. 18, 125–138 (2020).

    CAS  PubMed  Google Scholar 

  41. 41.

    Koonin, E. V. et al. Global organization and proposed megataxonomy of the virus world. Microbiol. Mol. Biol. Rev. 84, e00061-19 (2020).

    PubMed  PubMed Central  Google Scholar 

  42. 42.

    Al-Shayeb, B. et al. Clades of huge phages from across earth’s ecosystems. Nature 578, 425–431 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Ackermann, H. W. in The Bacteriophages 2nd edn (ed. Calendar, R. L.) 8–16 (Oxford Univ. Press, 2006).

  44. 44.

    Goldberg, E. B. in Bacteriophage T4 (eds Mathews, C. K., Kutter, E. M., Mosig, G. & Berget, P. B.) 32–39 (American Society for Microbiology, 1983).

  45. 45.

    Shkoporov, A. N. et al. The human gut virome is highly diverse, stable, and individual specific. Cell Host Microbe 26, 527–541 (2019).

    CAS  PubMed  Google Scholar 

  46. 46.

    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).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Goldberg, E. B. in Receptors and Recognition (Series B, Volume 7): Virus Receptors (Part 1: Bacterial Viruses) (eds Yamamura, H. I. & Enna, S. J.) 115–141 (Chapman & Hall, 1981).

  48. 48.

    Campbell, A. The future of bacteriophage biology. Nat. Rev. Genet. 4, 471–477 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. 49.

    Ofir, G. & Sorek, R. Contemporary phage biology: from classic models to new insights. Cell 172, 1260–1270 (2018).

    CAS  PubMed  Google Scholar 

  50. 50.

    Lindberg, A. A. Bacteriophage receptors. Annu. Rev. Microbiol. 27, 205–241 (1973).

    CAS  PubMed  Google Scholar 

  51. 51.

    Ge, H. et al. The “fighting wisdom and bravery” of tailed phage and host in the process of adsorption. Microbiol. Res. 230, 126344 (2020).

    PubMed  Google Scholar 

  52. 52.

    Silva, J. B., Storms, Z. & Sauvageau, D. Host receptors for bacteriophage adsorption. FEMS Microbiol. Lett. 363, fnw002 (2016).

    Google Scholar 

  53. 53.

    Young, R. Bacteriophage lysis: mechanism and regulation. Microbiol. Rev. 56, 430–481 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Cahill, J. & Young, R. in Advances in Virus Research Vol. 103 Ch. 2 (eds Kielian, M., Mettenleiter, T. C. & Roosinck, M. J.) 33–70 (Academic Press, 2019).

  55. 55.

    Zeng, L. et al. Decision making at a subcellular level determines the outcome of bacteriophage infection. Cell 141, 682–691 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Dou, C. et al. Structural and functional insights into the regulation of the lysis–lysogeny decision in viral communities. Nat. Microbiol. 3, 1285–1294 (2018).

    CAS  PubMed  Google Scholar 

  57. 57.

    Feiner, R. et al. A new perspective on lysogeny: prophages as active regulatory switches of bacteria. Nat. Rev. Microbiol. 13, 641–650 (2015).

    CAS  PubMed  Google Scholar 

  58. 58.

    Howard-Varona, C., Hargreaves, K. R., Abedon, S. T. & Sullivan, M. B. Lysogeny in nature: mechanisms, impact and ecology of temperate phages. ISME J. 11, 1511–1520 (2017).

    PubMed  PubMed Central  Google Scholar 

  59. 59.

    Bondy-Denomy, J. et al. Prophages mediate defense against phage infection through diverse mechanisms. ISME J. 10, 2854–2866 (2016).

    PubMed  PubMed Central  Google Scholar 

  60. 60.

    Fortier, L. C. & Sekulovic, O. Importance of prophages to evolution and virulence of bacterial pathogens. Virulence 4, 354–365 (2013).

    PubMed  PubMed Central  Google Scholar 

  61. 61.

    Banks, D. J., Lei, B. & Musser, J. M. Prophage induction and expression of prophage-encoded virulence factors in group A Streptococcus serotype M3 strain MGAS315. Infect. Immun. 71, 7079–7086 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. 62.

    Goerke, C., Köller, J. & Wolz, C. Ciprofloxacin and trimethoprim cause phage induction and virulence modulation in Staphylococcus aureus. Antimicrob. Agents Chemother. 50, 171–177 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. 63.

    Choi, J., Kotay, S. M. & Goel, R. Various physico-chemical stress factors cause prophage induction in Nitrosospira multiformis 25196–an ammonia oxidizing bacteria. Water Res. 44, 4550–4558 (2010).

    CAS  PubMed  Google Scholar 

  64. 64.

    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).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. 65.

    Nanda, A. M., Thormann, K. & Frunzke, J. Impact of spontaneous prophage induction on the fitness of bacterial populations and host–microbe interactions. J. Bacteriol. 197, 410–419 (2015).

    PubMed  PubMed Central  Google Scholar 

  66. 66.

    Labrie, S. J., Samson, J. E. & Moineau, S. Bacteriophage resistance mechanisms. Nat. Rev. Microbiol. 8, 317–327 (2010).

    CAS  PubMed  Google Scholar 

  67. 67.

    Samson, J. E., Magadán, A. H., Sabri, M. & Moineau, S. Revenge of the phages: defeating bacterial defences. Nat. Rev. Microbiol. 11, 675–687 (2013).

    CAS  PubMed  Google Scholar 

  68. 68.

    Ackermann, H. W. & Dubow, M. S. Viruses of Prokaryotes Vol. 1: General Properties of Bacteriophages 49–85 (CRC Press, 1987).

  69. 69.

    Dufour, N. et al. Bacteriophage LM33_P1, a fast-acting weapon against the pandemic ST131-O25b:H4 Escherichia coli clonal complex. J. Antimicrob. Chemother. 71, 3072–3080 (2016).

    CAS  PubMed  Google Scholar 

  70. 70.

    Kaiser, D. & Dworkin, M. Gene transfer to myxobacterium by Escherichia coli phage P1. Science 187, 653–654 (1975).

    CAS  PubMed  Google Scholar 

  71. 71.

    Qin, J. et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464, 59–65 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. 72.

    Huttenhower, C. et al. Structure, function and diversity of the healthy human microbiome. Nature 486, 207–214 (2012).

    CAS  Google Scholar 

  73. 73.

    Lloyd-Price, J. et al. Strains, functions and dynamics in the expanded Human Microbiome Project. Nature 550, 61–66 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. 74.

    Arumugam, M. et al. Enterotypes of the human gut microbiome. Nature 473, 174–180 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. 75.

    Lourenço, M. et al. The spatial heterogeneity of the gut limits predation and fosters coexistence of bacteria and bacteriophages. Cell Host Microbe 28, 390–401 (2020).

    PubMed  Google Scholar 

  76. 76.

    Sender, R., Fuchs, S. & Milo, R. Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans. Cell 164, 337–340 (2016).

    CAS  PubMed  Google Scholar 

  77. 77.

    Breitbart, M. et al. Metagenomic analyses of an uncultured viral community from human feces. J. Bacteriol. 185, 6220–6223 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. 78.

    Kim, M. S., Park, E. J., Roh, S. W. & Bae, J. W. Diversity and abundance of single-stranded DNA viruses in human feces. Appl. Environ. Microbiol. 77, 8062–8070 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. 79.

    Liang, G. et al. The stepwise assembly of the neonatal virome is modulated by breastfeeding. Nature 581, 470–474 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. 80.

    Reyes, A. et al. Gut DNA viromes of Malawian twins discordant for severe acute malnutrition. Proc. Natl Acad. Sci. USA 112, 11941–11946 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. 81.

    Lim, E. S. et al. Early life dynamics of the human gut virome and bacterial microbiome in infants. Nat. Med. 21, 1228–1234 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. 82.

    Lim, E. S., Wang, D. & Holtz, L. R. The bacterial microbiome and virome milestones of infant development. Trends Microbiol. 24, 801–810 (2016).

    CAS  PubMed  Google Scholar 

  83. 83.

    Edwards, R. A. et al. Global phylogeography and ancient evolution of the widespread human gut virus crAssphage. Nat. Microbiol. 4, 1727–1736 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. 84.

    Moreno-Gallego, J. L. et al. Virome diversity correlates with intestinal microbiome diversity in adult monozygotic twins. Cell Host Microbe 25, 261–272 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. 85.

    Tap, J. et al. Towards the human intestinal microbiota phylogenetic core. Environ. Microbiol. 11, 2574–2584 (2009).

    PubMed  Google Scholar 

  86. 86.

    Pedulla, M. L. et al. Origins of highly mosaic mycobacteriophage genomes. Cell 113, 171–182 (2003).

    CAS  PubMed  Google Scholar 

  87. 87.

    Deng, L. et al. Viral tagging reveals discrete populations in Synechococcus viral genome sequence space. Nature 513, 242–245 (2014).

    CAS  PubMed  Google Scholar 

  88. 88.

    Mavrich, T. N. & Hatfull, G. F. Bacteriophage evolution differs by host, lifestyle and genome. Nat. Microbiol. 2, 17112 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. 89.

    Hendrix, R. W., Smith, M. C. M., Burns, R. N., Ford, M. E. & Hatfull, G. F. Evolutionary relationships among diverse bacteriophages and prophages: all the world’s a phage. Proc. Natl Acad. Sci. USA 96, 2192–2197 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. 90.

    Shapiro, J. W. & Putonti, C. Gene co-occurrence networks reflect bacteriophage ecology and evolution. mBio 9, e01870-17 (2018).

    PubMed  PubMed Central  Google Scholar 

  91. 91.

    Shkoporov, A. N. et al. Reproducible protocols for metagenomic analysis of human faecal phageomes. Microbiome 6, 68 (2018).

    PubMed  PubMed Central  Google Scholar 

  92. 92.

    Conceição-Neto, N. et al. Modular approach to customise sample preparation procedures for viral metagenomics: a reproducible protocol for virome analysis. Sci. Rep. 5, 16532 (2015).

    PubMed  PubMed Central  Google Scholar 

  93. 93.

    Waller, A. S. et al. Classification and quantification of bacteriophage taxa in human gut metagenomes. ISME J. 8, 1391–1402 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. 94.

    Ma, Y., You, X., Mai, G., Tokuyasu, T. & Liu, C. A human gut phage catalog correlates the gut phageome with type 2 diabetes. Microbiome 6, 24 (2018).

    PubMed  PubMed Central  Google Scholar 

  95. 95.

    Kleiner, M., Hooper, L. V. & Duerkop, B. A. Evaluation of methods to purify virus-like particles for metagenomic sequencing of intestinal viromes. BMC Genomics 16, 7 (2015).

    PubMed  PubMed Central  Google Scholar 

  96. 96.

    Flewett, T. H., Bryden, A. S. & Davies, H. Diagnostic electron microscopy of faeces. J. Clin. Pathol. 27, 603–608 (1974).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. 97.

    Kim, K. H. & Bae, J. W. Amplification methods bias metagenomic libraries of uncultured single-stranded and double-stranded DNA viruses. Appl. Environ. Microbiol. 77, 7663–7668 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. 98.

    Yilmaz, S., Allgaier, M. & Hugenholtz, P. Multiple displacement amplification compromises quantitative analysis of metagenomes. Nat. Methods 7, 943–944 (2010).

    CAS  PubMed  Google Scholar 

  99. 99.

    Roux, S. et al. Towards quantitative viromics for both double-stranded and single-stranded DNA viruses. PeerJ 4, e2777 (2016).

    PubMed  PubMed Central  Google Scholar 

  100. 100.

    Krishnamurthy, S. R. & Wang, D. Origins and challenges of viral dark matter. Virus Res. 239, 136–142 (2017).

    CAS  PubMed  Google Scholar 

  101. 101.

    Santiago-Rodriguez, T. M. & Hollister, E. B. Human virome and disease: high-throughput sequencing for virus discovery, identification of phage-bacteria dysbiosis and development of therapeutic approaches with emphasis on the human gut. Viruses 11, 656 (2019).

    CAS  PubMed Central  Google Scholar 

  102. 102.

    Barr, J. J. et al. Bacteriophage adhering to mucus provide a non–host-derived immunity. Proc. Natl Acad. Sci. USA 110, 10771–10776 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. 103.

    Wagner, J. et al. Bacteriophages in gut samples from pediatric Crohn’s disease patients: metagenomic analysis using 454 pyrosequencing. Inflamm. Bowel Dis. 19, 1598–1608 (2013).

    PubMed  Google Scholar 

  104. 104.

    Siringan, P., Connerton, P. L., Cummings, N. J. & Connerton, I. F. Alternative bacteriophage life cycles: the carrier state of Campylobacter jejuni. Open. Biol. 4, 130200 (2014).

    PubMed  PubMed Central  Google Scholar 

  105. 105.

    Pourcel, C., Midoux, C., Vergnaud, G. & Latino, L. A carrier state is established in Pseudomonas aeruginosa by phage LeviOr01, a newly isolated ssRNA levivirus. J. Gen. Virol. 98, 2181–2189 (2017).

    CAS  PubMed  Google Scholar 

  106. 106.

    Joossens, M. et al. Dysbiosis of the faecal microbiota in patients with Crohn’s disease and their unaffected relatives. Gut 60, 631–637 (2011).

    PubMed  Google Scholar 

  107. 107.

    Lax, S. et al. Longitudinal analysis of microbial interaction between humans and the indoor environment. Science 345, 1048–1052 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  108. 108.

    Zmora, N., Suez, J. & Elinav, E. You are what you eat: diet, health and the gut microbiota. Nat. Rev. Gastroenterol. Hepatol. 16, 35–56 (2019).

    CAS  PubMed  Google Scholar 

  109. 109.

    Minot, S. et al. The human gut virome: inter-individual variation and dynamic response to diet. Genome Res. 21, 1616–1625 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  110. 110.

    Zuo, T. et al. Human-gut-DNA virome variations across geography, ethnicity, and urbanization. Cell Host Microbe 28, 741–751 (2020).

    CAS  PubMed  Google Scholar 

  111. 111.

    Coughlan, S. et al. The gut virome in irritable bowel syndrome differs from that of controls. Gut Microbes 13, 1–15 (2021).

    CAS  PubMed  Google Scholar 

  112. 112.

    Lepage, P. et al. Dysbiosis in inflammatory bowel disease: a role for bacteriophages? Gut 57, 424–425 (2008).

    CAS  PubMed  Google Scholar 

  113. 113.

    Bajaj, J. S. et al. Interaction of bacterial metagenome and virome in patients with cirrhosis and hepatic encephalopathy. Gut 70, 1162–1173 (2021).

    CAS  PubMed  Google Scholar 

  114. 114.

    d’Herelle, F. & Smith, G. H. The bacteriophage and its behavior 490–497 (Williams & Wilkins, 1926).

  115. 115.

    Spence, R. C. & Mckinley, E. B. The therapeutic value of the bacteriophage in treatment of bacillary dysentery. South. Med. J. 17, 563–571 (1924).

    Google Scholar 

  116. 116.

    Burnet, F. M., McKie, M. & Wood, I. J. Investigations on bacillary dysentery in infants, with special reference to bacteriophage phenomena. Med. J. Aust. 2, 71–78 (1930).

    Google Scholar 

  117. 117.

    D’Herelle, F. Studies upon Asiatic cholera. Yale J. Biol. Med. 1, 195–219 (1929).

    PubMed  PubMed Central  Google Scholar 

  118. 118.

    Becherich, A. & Hauduroy, P. Le bactériophage dans le traitement de la fièvre typhoïde [French]. C. R. Soc. Biol. 86, 168–170 (1922).

    Google Scholar 

  119. 119.

    Smith, J. The bacteriophage in the treatment of typhoid fever. Br. Med. J. 2, 47–49 (1924).

    CAS  PubMed  PubMed Central  Google Scholar 

  120. 120.

    Hadley, P. The Twort-D’Herelle phenomenon: a critical review and presentation of a new conception (homogamic theory) of bacteriophage action. J. Infect. Dis. 42, 263–434 (1928).

    Google Scholar 

  121. 121.

    Eaton, M. D. & Bayne-Jones, S. Bacteriophage therapy: review of the principles and results of the use of bacteriophage in the treatment of infections. J. Am. Med. Assoc. 103, 1769–1776 (1934).

    CAS  Google Scholar 

  122. 122.

    Merabishvili, M. et al. Quality-controlled small-scale production of a well-defined bacteriophage cocktail for use in human clinical trials. PLoS ONE 4, e4944 (2009).

    PubMed  PubMed Central  Google Scholar 

  123. 123.

    Bruttin, A. & Brüssow, H. Human volunteers receiving Escherichia coli phage T4 orally: a safety test of phage therapy. Antimicrob. Agents Chemother. 49, 2874–2878 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. 124.

    Sarker, S. A. et al. Oral T4-like phage cocktail application to healthy adult volunteers from Bangladesh. Virology 434, 222–232 (2012).

    CAS  PubMed  Google Scholar 

  125. 125.

    McCallin, S. et al. Safety analysis of a Russian phage cocktail: from metagenomic analysis to oral application in healthy human subjects. Virology 443, 187–196 (2013).

    CAS  PubMed  Google Scholar 

  126. 126.

    Sarker, S. A. et al. Oral application of Escherichia coli bacteriophage: safety tests in healthy and diarrheal children from Bangladesh. Environ. Microbiol. 19, 237–250 (2017).

    CAS  PubMed  Google Scholar 

  127. 127.

    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).

    PubMed  PubMed Central  Google Scholar 

  128. 128.

    Schooley, R. T. et al. Development and use of personalized bacteriophage-based therapeutic cocktails to treat a patient with a disseminated resistant Acinetobacter baumannii infection. Antimicrob. Agents Chemother. 61, e00954-17 (2017).

    PubMed  PubMed Central  Google Scholar 

  129. 129.

    Jennes, S. et al. Use of bacteriophages in the treatment of colistin-only-sensitive Pseudomonas aeruginosa septicaemia in a patient with acute kidney injury–a case report. Crit. Care 21, 129 (2017).

    PubMed  PubMed Central  Google Scholar 

  130. 130.

    Dedrick, R. M. et al. Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus. Nat. Med. 25, 730–733 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  131. 131.

    Yen, M., Cairns, L. S. & Camilli, A. A cocktail of three virulent bacteriophages prevents Vibrio cholerae infection in animal models. Nat. Commun. 8, 14187 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  132. 132.

    Faruque, S. M. et al. Self-limiting nature of seasonal cholera epidemics: role of host-mediated amplification of phage. Proc. Natl Acad. Sci. USA 102, 6119–6124 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  133. 133.

    Khoruts, A. & Sadowsky, M. J. Understanding the mechanisms of faecal microbiota transplantation. Nat. Rev. Gastroenterol. Hepatol. 13, 508–516 (2016).

    PubMed  PubMed Central  Google Scholar 

  134. 134.

    Sanders, M. E., Merenstein, D. J., Reid, G., Gibson, G. R. & Rastall, R. A. Probiotics and prebiotics in intestinal health and disease: from biology to the clinic. Nat. Rev. Gastroenterol. Hepatol. 16, 605–616 (2019).

    PubMed  Google Scholar 

  135. 135.

    Deaton, J., Ertle, E. & Dawson, H. G. Prebiotic compositions comprising one or more types of bacteriophage. US Patent 9,839,657 (2017).

  136. 136.

    Gindin, M., Febvre, H. P., Rao, S., Wallace, T. C. & Weir, T. L. Bacteriophage for Gastrointestinal Health (PHAGE) study: evaluating the safety and tolerability of supplemental bacteriophage consumption. J. Am. Coll. Nutr. 38, 68–75 (2019).

    CAS  PubMed  Google Scholar 

  137. 137.

    Grubb, D. S. et al. PHAGE-2 study: supplemental bacteriophages extend Bifidobacterium animalis subsp. lactis BL04 benefits on gut health and microbiota in healthy adults. Nutrients 12, 2474 (2020).

    CAS  PubMed Central  Google Scholar 

  138. 138.

    Rolhion, N. & Darfeuille-Michaud, A. Adherent-invasive Escherichia coli in inflammatory bowel disease. Inflamm. Bowel Dis. 13, 1277–1283 (2007).

    PubMed  Google Scholar 

  139. 139.

    Palmela, C. et al. Adherent-invasive Escherichia coli in inflammatory bowel disease. Gut 67, 574–587 (2018).

    CAS  PubMed  Google Scholar 

  140. 140.

    Galtier, M. et al. Bacteriophages targeting adherent invasive Escherichia coli strains as a promising new treatment for Crohn’s disease. J. Crohn’s Colitis 11, 840–847 (2017).

    Google Scholar 

  141. 141.

    Duan, Y. et al. Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease. Nature 575, 505–511 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  142. 142.

    McCoy, W. C. & Mason, J. M. 3rd Enterococcal endocarditis associated with carcinoma of the sigmoid; report of a case. J. Med. Assoc. State Ala. 21, 162–166 (1951).

    CAS  PubMed  Google Scholar 

  143. 143.

    Abdulamir, A. S., Hafidh, R. R. & Bakar, F. A. The association of Streptococcus bovis/gallolyticus with colorectal tumors: the nature and the underlying mechanisms of its etiological role. J. Exp. Clin. Cancer Res. 30, 11 (2011).

    PubMed  PubMed Central  Google Scholar 

  144. 144.

    Boleij, A., van Gelder, M. M. H. J., Swinkels, D. W. & Tjalsma, H. Clinical importance of Streptococcus gallolyticus infection among colorectal cancer patients: systematic review and meta-analysis. Clin. Infect. Dis. 53, 870–878 (2011).

    CAS  PubMed  Google Scholar 

  145. 145.

    Wirbel, J. et al. Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer. Nat. Med. 25, 679–689 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  146. 146.

    Yachida, S. et al. Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer. Nat. Med. 25, 968–976 (2019).

    CAS  PubMed  Google Scholar 

  147. 147.

    Wong, S. H. et al. Quantitation of faecal Fusobacterium improves faecal immunochemical test in detecting advanced colorectal neoplasia. Gut 66, 1441–1448 (2017).

    CAS  PubMed  Google Scholar 

  148. 148.

    Castellarin, M. et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 22, 299–306 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  149. 149.

    Kostic, A. D. et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe 14, 207–215 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  150. 150.

    Bullman, S. et al. Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer. Science 358, 1443–1448 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  151. 151.

    Wu, S. et al. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat. Med. 15, 1016–1022 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  152. 152.

    Arthur, J. C. et al. Intestinal inflammation targets cancer-inducing activity of the microbiota. Science 338, 120–123 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  153. 153.

    Dejea, C. M. et al. Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria. Science 359, 592–597 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  154. 154.

    Huycke, M. M., Abrams, V. & Moore, D. R. Enterococcus faecalis produces extracellular superoxide and hydrogen peroxide that damages colonic epithelial cell DNA. Carcinogenesis 23, 529–536 (2002).

    CAS  PubMed  Google Scholar 

  155. 155.

    Wang, X. et al. 4-Hydroxy-2-nonenal mediates genotoxicity and bystander effects caused by Enterococcus faecalis–infected macrophages. Gastroenterology 142, 543–551 (2012).

    CAS  PubMed  Google Scholar 

  156. 156.

    Kumar, R. et al. Streptococcus gallolyticus subsp. gallolyticus promotes colorectal tumor development. PLoS Pathog. 13, e1006440 (2017).

    PubMed  PubMed Central  Google Scholar 

  157. 157.

    Zhu, W. et al. Editing of the gut microbiota reduces carcinogenesis in mouse models of colitis-associated colorectal cancer. J. Exp. Med. 216, 2378–2393 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  158. 158.

    Henning, U. et al. in Molecular Biology of Bacteriophage T4 Vol. 1 Ch. 23 (ed. Karam, J. D.) 291–298 (ASM Press, 1994).

  159. 159.

    Iida, S. Bacteriophage P1 carries two related sets of genes determining its host range in the invertible C segment of its genome. Virology 134, 421–434 (1984).

    CAS  PubMed  Google Scholar 

  160. 160.

    Summer, E. J. et al. Burkholderia cenocepacia phage BcepMu and a family of Mu-like phages encoding potential pathogenesis factors. J. Mol. Biol. 340, 49–65 (2004).

    CAS  PubMed  Google Scholar 

  161. 161.

    Liu, M. et al. Reverse transcriptase-mediated tropism switching in Bordetella bacteriophage. Science 295, 2091–2094 (2002).

    CAS  PubMed  Google Scholar 

  162. 162.

    Bar, H., Yacoby, I. & Benhar, I. Killing cancer cells by targeted drug-carrying phage nanomedicines. BMC Biotechnol. 8, 37 (2008).

    PubMed  PubMed Central  Google Scholar 

  163. 163.

    Yacoby, I., Shamis, M., Bar, H., Shabat, D. & Benhar, I. Targeting antibacterial agents by using drug-carrying filamentous bacteriophages. Antimicrob. Agents Chemother. 50, 2087–2097 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  164. 164.

    Yacoby, I., Bar, H. & Benhar, I. Targeted drug-carrying bacteriophages as antibacterial nanomedicines. Antimicrob. Agents Chemother. 51, 2156–2163 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  165. 165.

    Vaks, L. & Benhar, I. in Biomedical Nanotechnology: Methods in Molecular Biology (Methods and Protocols) Vol. 726 (ed. Hurst, S.) 187–206 (Humana Press, 2011).

  166. 166.

    Zheng, D. W. et al. Phage-guided modulation of the gut microbiota of mouse models of colorectal cancer augments their responses to chemotherapy. Nat. Biomed. Eng. 3, 717–728 (2019).

    CAS  PubMed  Google Scholar 

  167. 167.

    Yu, T. C. et al. Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy. Cell 170, 548–563 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  168. 168.

    Dong, X. et al. Bioinorganic hybrid bacteriophage for modulation of intestinal microbiota to remodel tumor-immune microenvironment against colorectal cancer. Sci. Adv. 6, eaba1590 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  169. 169.

    Devkota, S. et al. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10−/− mice. Nature 487, 104–108 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  170. 170.

    Hendrikx, T. et al. Bacteria engineered to produce IL-22 in intestine induce expression of REG3G to reduce ethanol-induced liver disease in mice. Gut 68, 1504–1515 (2019).

    CAS  PubMed  Google Scholar 

  171. 171.

    Singh, N. et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity 40, 128–139 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  172. 172.

    Cani, P. D. & Jordan, B. F. Gut microbiota-mediated inflammation in obesity: a link with gastrointestinal cancer. Nat. Rev. Gastroenterol. Hepatol. 15, 671–682 (2018).

    CAS  PubMed  Google Scholar 

  173. 173.

    Febvre, H. P. et al. PHAGE study: effects of supplemental bacteriophage intake on inflammation and gut microbiota in healthy adults. Nutrients 11, 666 (2019).

    CAS  PubMed Central  Google Scholar 

  174. 174.

    Sweere, J. M. et al. Bacteriophage trigger antiviral immunity and prevent clearance of bacterial infection. Science 363, eaat9691 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  175. 175.

    Tetz, G. V. et al. Bacteriophages as potential new mammalian pathogens. Sci. Rep. 7, 7043 (2017).

    PubMed  PubMed Central  Google Scholar 

  176. 176.

    Van Belleghem, J. D., Clement, F., Merabishvili, M., Lavigne, R. & Vaneechoutte, M. Pro- and anti-inflammatory responses of peripheral blood mononuclear cells induced by Staphylococcus aureus and Pseudomonas aeruginosa phages. Sci. Rep. 7, 8004 (2017).

    PubMed  PubMed Central  Google Scholar 

  177. 177.

    Gogokhia, L. et al. Expansion of bacteriophages is linked to aggravated intestinal inflammation and colitis. Cell Host Microbe 25, 285–299 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  178. 178.

    Zhang, L. et al. Staphylococcus aureus bacteriophage suppresses LPS-induced inflammation in MAC-T bovine mammary epithelial cells. Front. Microbiol. 9, 1614 (2018).

    PubMed  PubMed Central  Google Scholar 

  179. 179.

    Hong, Y. et al. The impact of orally administered phages on host immune response and surrounding microbial communities. Bacteriophage 6, e1211066 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  180. 180.

    Miernikiewicz, P. et al. T4 phage and its head surface proteins do not stimulate inflammatory mediator production. PLoS ONE 8, e71036 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  181. 181.

    Merabishvili, M., Pirnay, J. P. & De Vos, D. in Bacteriophage Therapy: From Lab to Clinical Practice (eds Azeredo, J. & Sillankorva, S.) 99–110 (Springer, 2018).

  182. 182.

    Betts, A., Vasse, M., Kaltz, O. & Hochberg, M. E. Back to the future: evolving bacteriophages to increase their effectiveness against the pathogen Pseudomonas aeruginosa PAO1. Evolut. Appl. 6, 1054–1063 (2013).

    Google Scholar 

  183. 183.

    Friman, V. P. et al. Pre-adapting parasitic phages to a pathogen leads to increased pathogen clearance and lowered resistance evolution with Pseudomonas aeruginosa cystic fibrosis bacterial isolates. J. Evolut. Biol. 29, 188–198 (2016).

    Google Scholar 

  184. 184.

    Dunne, M. et al. Reprogramming bacteriophage host range through structure-guided design of chimeric receptor binding proteins. Cell Rep. 29, 1336–1350 (2019).

    CAS  PubMed  Google Scholar 

  185. 185.

    Yehl, K. et al. Engineering phage host-range and suppressing bacterial resistance through phage tail fiber mutagenesis. Cell 179, 459–469 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  186. 186.

    Ly-Chatain, M. H. The factors affecting effectiveness of treatment in phages therapy. Front. Microbiol. 5, 51 (2014).

    PubMed  PubMed Central  Google Scholar 

  187. 187.

    Cui, Z., Guo, X., Feng, T. & Li, L. Exploring the whole standard operating procedure for phage therapy in clinical practice. J. Transl. Med. 17, 373 (2019).

    PubMed  PubMed Central  Google Scholar 

  188. 188.

    Fabijan, A. P. et al. Safety of bacteriophage therapy in severe Staphylococcus aureus infection. Nat. Microbiol. 5, 465–472 (2020).

    Google Scholar 

  189. 189.

    Jończyk, E., Kłak, M., Międzybrodzki, R. & Górski, A. The influence of external factors on bacteriophages–review. Folia Microbiol. 56, 191–200 (2011).

    Google Scholar 

  190. 190.

    Colom, J. et al. Microencapsulation with alginate/CaCO3: a strategy for improved phage therapy. Sci. Rep. 7, 41441 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  191. 191.

    Hsu, B. B. et al. In situ reprogramming of gut bacteria by oral delivery. Nat. Commun. 11, 5030 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  192. 192.

    Dąbrowska, K. Phage therapy: what factors shape phage pharmacokinetics and bioavailability? Systematic and critical review. Med. Res. Rev. 39, 2000–2025 (2019).

    PubMed  PubMed Central  Google Scholar 

  193. 193.

    Srivastava, A. S., Kaido, T. & Carrier, E. Immunological factors that affect the in vivo fate of T7 phage in the mouse. J. Virol. Meth. 115, 99–104 (2004).

    CAS  Google Scholar 

  194. 194.

    Merril, C. R. et al. Long-circulating bacteriophage as antibacterial agents. Proc. Natl Acad. Sci. USA 93, 3188–3192 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  195. 195.

    Capparelli, R., Parlato, M., Borriello, G., Salvatore, P. & Iannelli, D. Experimental phage therapy against Staphylococcus aureus in mice. Antimicrob. Agents Chemother. 51, 2765–2773 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  196. 196.

    Capparelli, R., Ventimiglia, I., Roperto, S., Fenizia, D. & Iannelli, D. Selection of an Escherichia coli O157:H7 bacteriophage for persistence in the circulatory system of mice infected experimentally. Clin. Microbiol. Infect. 12, 248–253 (2006).

    CAS  PubMed  Google Scholar 

  197. 197.

    Fauconnier, A. in Bacteriophage Therapy: From Lab to Clinical Practice (eds Azeredo, J. & Sillankorva, S.) 253–268 (Springer, 2018).

  198. 198.

    Pirnay, J. P. et al. The phage therapy paradigm: prêt-à-porter or sur-mesure? Pharm. Res. 28, 934–937 (2011).

    CAS  PubMed  Google Scholar 

  199. 199.

    Servick, K. Beleaguered phage therapy trial presses on. Science 352, 1506 (2016).

    CAS  PubMed  Google Scholar 

  200. 200.

    Pirnay, J. P. et al. The magistral phage. Viruses 10, 64 (2018).

    PubMed Central  Google Scholar 

  201. 201.

    EUR-Lex. Opinion of Advocate General Szpunar delivered on 30 June 2016. Case C-276/15: Hecht-Pharma GmbH v Hohenzollern Apotheke, owned by Winfried Ertelt. EUR-Lex https://eur-lex.europa.eu/legal-content/en/TXT/?uri=CELEX:62015CC0276 (2016).

  202. 202.

    Corbellino, M. et al. Eradication of a multidrug-resistant, carbapenemase-producing Klebsiella pneumoniae isolate following oral and intra-rectal therapy with a custom made, lytic bacteriophages preparation. Clin. Infect. Dis. 70, 1998–2001 (2020).

    CAS  PubMed  Google Scholar 

  203. 203.

    US National Library of Medicine. ClinicalTrials.gov https://www.clinicaltrials.gov/ct2/show/NCT03808103 (2021).

Download references

Acknowledgements

B.S. was supported in part by a Biocodex Microbiota Foundation Grant, NIH grants R01 AA024726, U01 AA026939, by Award Number BX004594 from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development and services provided by P30 DK120515 and P50 AA011999.

Author information

Affiliations

Authors

Contributions

Y.D. researched data for the article, made a substantial contribution to discussion of content, wrote the article, and reviewed/edited the manuscript before submission. R.Y. and B.S. made a substantial contribution to discussion of content and reviewed/edited the manuscript before submission.

Corresponding author

Correspondence to Bernd Schnabl.

Ethics declarations

Competing interests

B.S. has been consulting for Ferring Research Institute, Intercept Pharmaceuticals, HOST Therabiomics, Mabwell Therapeutics, Patara Pharmaceuticals and Takeda. B.S.’s institution UC San Diego has received grant support from BiomX, NGM Biopharmaceuticals, CymaBay Therapeutics, Synlogic Operating Company, Prodigy Biotech and Axial Biotherapeutics. B.S. is founder of Nterica Bio. UC San Diego has filed several patents with B.S. and Y.D. as inventors related to this work. R.Y. was formerly involved with GangaGen (Bangalore, India) as a member of its scientific advisory board.

Additional information

Peer review information

Nature Reviews Gastroenterology & Hepatology thanks Harald Brüssow, Laurent Debarbieux and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Duan, Y., Young, R. & Schnabl, B. Bacteriophages and their potential for treatment of gastrointestinal diseases. Nat Rev Gastroenterol Hepatol 19, 135–144 (2022). https://doi.org/10.1038/s41575-021-00536-z

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41575-021-00536-z

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing