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The Human Gut-Liver-Axis in Health and Disease pp 121–131Cite as

The Role of the Virome in the Gut-Liver Axis

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Abstract

Eukaryotic and prokaryotic viruses have been recognized as an important part and driver of the human gut microbiota within the past decades and are even present in greater numbers than bacteria. Unfortunately, viruses are much harder to study than bacteria, but improvements in laboratory techniques, sequencing and bioinformatics have paved the way for studies elucidating the impact of viruses on human health and disease. The viral genomes of the human gut are collectively called the virome and this chapter will outline the challenges in studying these, the difference between eukaryotic and prokaryotic viruses and the impact of viruses on human health and disease, with a focus on how the virome impacts patients with chronic liver disease.

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References

  1. Anand G, Zarrinpar A, Loomba R. Targeting dysbiosis for the treatment of liver disease. Semin Liver Dis. 2016;36:37–47.

    Article  CAS  Google Scholar 

  2. Barr JJ, Youle M, Rohwer F. Innate and acquired bacteriophage-mediated immunity. Bacteriophage. 2013;3:e25857.

    Article  Google Scholar 

  3. Barton ES, White DW, Cathelyn JS, Brett-McClellan KA, Engle M, Diamond MS, Miller VL, Virgin HW. Herpesvirus latency confers symbiotic protection from bacterial infection. Nature. 2007;447:326–9.

    Article  CAS  Google Scholar 

  4. Bhattarai N, Stapleton JT. GB virus C: the good boy virus? Trends Microbiol. 2012;20:124–30.

    Article  CAS  Google Scholar 

  5. Bischoff SC, Barbara G, Buurman W, Ockhuizen T, Schulzke JD, Serino M, Tilg H, Watson A, Wells JM. Intestinal permeability – a new target for disease prevention and therapy. BMC Gastroenterol. 2014;14:189.

    Article  Google Scholar 

  6. Blum HE. The human microbiome. Adv Med Sci. 2017;62:414–20.

    Article  Google Scholar 

  7. Brussow H, Hendrix RW. Phage genomics: small is beautiful. Cell. 2002;108:13–6.

    Article  CAS  Google Scholar 

  8. Bruttin A, Brussow H. Human volunteers receiving Escherichia coli phage T4 orally: a safety test of phage therapy. Antimicrob Agents Chemother. 2005;49:2874–8.

    Article  CAS  Google Scholar 

  9. Cadwell K, Patel KK, Maloney NS, Liu TC, Ng AC, Storer CE, Head RD, Xavier R, Stappenbeck TS, Virgin HW. Virus-plus-susceptibility gene interaction determines Crohn’s disease gene Atg16L1 phenotypes in intestine. Cell. 2010;141:1135–45.

    Article  CAS  Google Scholar 

  10. Carding SR, Davis N, Hoyles L. Review article: the human intestinal virome in health and disease. Aliment Pharmacol Ther. 2017;46:800–15.

    Article  CAS  Google Scholar 

  11. Cenit MC, Sanz Y, Codoner-Franch P. Influence of gut microbiota on neuropsychiatric disorders. World J Gastroenterol. 2017;23:5486–98.

    Article  CAS  Google Scholar 

  12. Chen Y, Yang F, Lu H, Wang B, Chen Y, Lei D, Wang Y, Zhu B, Li L. Characterization of fecal microbial communities in patients with liver cirrhosis. Hepatology. 2011;54:562–72.

    Article  Google Scholar 

  13. Conceicao-Neto N, Deboutte W, Dierckx T, Machiels K, Wang J, Yinda CK, Maes P, Van Ranst M, Joossens M, Raes J, Vermeire S, Matthijnssens J. Low eukaryotic viral richness is associated with faecal microbiota transplantation success in ulcerative colitis patients. Gut. 2018;67(8):1558–9.

    Article  Google Scholar 

  14. Damgaard C, Magnussen K, Enevold C, Nilsson M, Tolker-Nielsen T, Holmstrup P, Nielsen CH. Viable bacteria associated with red blood cells and plasma in freshly drawn blood donations. PLoS One. 2015;10:e0120826.

    Article  Google Scholar 

  15. De Vlaminck I, Khush KK, Strehl C, Kohli B, Luikart H, Neff NF, Okamoto J, Snyder TM, Cornfield DN, Nicolls MR, Weill D, Bernstein D, Valantine HA, Quake SR. Temporal response of the human virome to immunosuppression and antiviral therapy. Cell. 2013;155:1178–87.

    Article  Google Scholar 

  16. Duerkop BA, Hooper LV. Resident viruses and their interactions with the immune system. Nat Immunol. 2013;14:654–9.

    Article  CAS  Google Scholar 

  17. Dutilh BE, Cassman N, McNair K, Sanchez SE, Silva GG, Boling L, Barr JJ, Speth DR, Seguritan V, Aziz RK, Felts B, Dinsdale EA, Mokili JL, Edwards RA. A highly abundant bacteriophage discovered in the unknown sequences of human faecal metagenomes. Nat Commun. 2014;5:4498.

    Article  CAS  Google Scholar 

  18. Festi D, Schiumerini R, Eusebi LH, Marasco G, Taddia M, Colecchia A. Gut microbiota and metabolic syndrome. World J Gastroenterol. 2014;20:16079–94.

    Article  Google Scholar 

  19. FitzSimons D, Hendrickx G, Vorsters A, Van Damme P. Hepatitis A and E: update on prevention and epidemiology. Vaccine. 2010;28:583–8.

    Article  Google Scholar 

  20. Gebbers JO, Laissue JA. Bacterial translocation in the normal human appendix parallels the development of the local immune system. Ann N Y Acad Sci. 2004;1029:337–43.

    Article  Google Scholar 

  21. Gorski A, Dabrowska K, Miedzybrodzki R, Weber-Dabrowska B, Lusiak-Szelachowska M, Jonczyk-Matysiak E, Borysowski J. Phages and immunomodulation. Future Microbiol. 2017;12:905–14.

    Article  CAS  Google Scholar 

  22. Gorski A, Jonczyk-Matysiak E, Lusiak-Szelachowska M, Miedzybrodzki R, Weber-Dabrowska B, Borysowski J. Bacteriophages targeting intestinal epithelial cells: a potential novel form of immunotherapy. Cell Mol Life Sci. 2018;75(4):589–95.

    Article  CAS  Google Scholar 

  23. Gorski A, Jonczyk-Matysiak E, Lusiak-Szelachowska M, Weber-Dabrowska B, Miedzybrodzki R, Borysowski J. Therapeutic potential of phages in autoimmune liver diseases. Clin Exp Immunol. 2018;192(1):1–6.

    Article  Google Scholar 

  24. Gorski A, Miedzybrodzki R, Borysowski J, Dabrowska K, Wierzbicki P, Ohams M, Korczak-Kowalska G, Olszowska-Zaremba N, Lusiak-Szelachowska M, Klak M, Jonczyk E, Kaniuga E, Golas A, Purchla S, Weber-Dabrowska B, Letkiewicz S, Fortuna W, Szufnarowski K, Pawelczyk Z, Rogoz P, Klosowska D. Phage as a modulator of immune responses: practical implications for phage therapy. Adv Virus Res. 2012;83:41–71.

    Article  CAS  Google Scholar 

  25. Gorski A, Wazna E, Dabrowska BW, Dabrowska K, Switala-Jelen K, Miedzybrodzki R. Bacteriophage translocation. FEMS Immunol Med Microbiol. 2006;46:313–9.

    Article  CAS  Google Scholar 

  26. Groschwitz KR, Hogan SP. Intestinal barrier function: molecular regulation and disease pathogenesis. J Allergy Clin Immunol. 2009;124:3–20. quiz 21–2.

    Article  CAS  Google Scholar 

  27. Guarner F, Malagelada JR. Gut flora in health and disease. Lancet. 2003;361:512–9.

    Article  Google Scholar 

  28. Handley SA, Thackray LB, Zhao G, Presti R, Miller AD, Droit L, Abbink P, Maxfield LF, Kambal A, Duan E, Stanley K, Kramer J, Macri SC, Permar SR, Schmitz JE, Mansfield K, Brenchley JM, Veazey RS, Stappenbeck TS, Wang D, Barouch DH, Virgin HW. Pathogenic simian immunodeficiency virus infection is associated with expansion of the enteric virome. Cell. 2012;151:253–66.

    Article  CAS  Google Scholar 

  29. Hoyles L, McCartney AL, Neve H, Gibson GR, Sanderson JD, Heller KJ, van Sinderen D. Characterization of virus-like particles associated with the human faecal and caecal microbiota. Res Microbiol. 2014;165:803–12.

    Article  CAS  Google Scholar 

  30. Kernbauer E, Ding Y, Cadwell K. An enteric virus can replace the beneficial function of commensal bacteria. Nature. 2014;516:94–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Kole A, Maloy KJ. Control of intestinal inflammation by interleukin-10. Curr Top Microbiol Immunol. 2014;380:19–38.

    CAS  PubMed  Google Scholar 

  32. Konig J, Wells J, Cani PD, Garcia-Rodenas CL, MacDonald T, Mercenier A, Whyte J, Troost F, Brummer RJ. Human intestinal barrier function in health and disease. Clin Transl Gastroenterol. 2016;7:e196.

    Article  Google Scholar 

  33. Lusiak-Szelachowska M, Weber-Dabrowska B, Jonczyk-Matysiak E, Wojciechowska R, Gorski A. Bacteriophages in the gastrointestinal tract and their implications. Gut Pathog. 2017;9:44.

    Article  Google Scholar 

  34. Mankiewicz E, Liivak M. Mycobacteriophages isolated from human sources. Nature. 1967;216:485–6.

    Article  CAS  Google Scholar 

  35. Mlynarczyk G, Garlinski P, Mlynarczyk A, Zabuska K, Sawicka-Grzelak A, Machowska G, Osowiecki H, Roszkowski W. Bacteriophage conversion as a factor modifying the intensity of phagocytosis of Staphylococcus aureus by human leukocytes. Med Dosw Mikrobiol. 1989;41:86–91.

    CAS  PubMed  Google Scholar 

  36. Mokili JL, Rohwer F, Dutilh BE. Metagenomics and future perspectives in virus discovery. Curr Opin Virol. 2012;2:63–77.

    Article  CAS  Google Scholar 

  37. Moustafa A, Xie C, Kirkness E, Biggs W, Wong E, Turpaz Y, Bloom K, Delwart E, Nelson KE, Venter JC, Telenti A. The blood DNA virome in 8,000 humans. PLoS Pathog. 2017;13:e1006292.

    Article  Google Scholar 

  38. Nelson DC. Phage classification for the 21st century. In: Life in our phage world. San Diego: Wholon; 2014. p. 8–19.

    Google Scholar 

  39. Nguyen S, Baker K, Padman BS, Patwa R, Dunstan RA, Weston TA, Schlosser K, Bailey B, Lithgow T, Lazarou M, Luque A, Rohwer F, Blumberg RS, Barr JJ. Bacteriophage transcytosis provides a mechanism to cross epithelial cell layers. MBio. 2018;9(1):e02207–17.

    Article  Google Scholar 

  40. Norman JM, Handley SA, Baldridge MT, Droit L, Liu CY, Keller BC, Kambal A, Monaco CL, Zhao G, Fleshner P, Stappenbeck TS, McGovern DP, Keshavarzian A, Mutlu EA, Sauk J, Gevers D, Xavier RJ, Wang D, Parkes M, Virgin HW. Disease-specific alterations in the enteric virome in inflammatory bowel disease. Cell. 2015;160:447–60.

    Article  CAS  Google Scholar 

  41. Ott SJ, Waetzig GH, Rehman A, Moltzau-Anderson J, Bharti R, Grasis JA, Cassidy L, Tholey A, Fickenscher H, Seegert D, Rosenstiel P, Schreiber S. Efficacy of sterile fecal filtrate transfer for treating patients with Clostridium difficile infection. Gastroenterology. 2017;152(799–811):e797.

    Google Scholar 

  42. Paisse S, Valle C, Servant F, Courtney M, Burcelin R, Amar J, Lelouvier B. Comprehensive description of blood microbiome from healthy donors assessed by 16S targeted metagenomic sequencing. Transfusion. 2016;56:1138–47.

    Article  CAS  Google Scholar 

  43. Pan W, Kang Y. Gut microbiota and chronic kidney disease: implications for novel mechanistic insights and therapeutic strategies. Int Urol Nephrol. 2018;50(2):289–99.

    Article  CAS  Google Scholar 

  44. Parent K, Wilson ID. Mycobacteriophage in Crohn’s disease. Gut. 1971;12:1019–20.

    Article  CAS  Google Scholar 

  45. Reyes A, Haynes M, Hanson N, Angly FE, Heath AC, Rohwer F, Gordon JI. Viruses in the faecal microbiota of monozygotic twins and their mothers. Nature. 2010;466:334–8.

    Article  CAS  Google Scholar 

  46. Reynaud A, Cloastre L, Bernard J, Laveran H, Ackermann HW, Licois D, Joly B. Characteristics and diffusion in the rabbit of a phage for Escherichia coli 0103. Attempts to use this phage for therapy. Vet Microbiol. 1992;30:203–12.

    Article  CAS  Google Scholar 

  47. Ringehan M, McKeating JA, Protzer U. Viral hepatitis and liver cancer. Philos Trans R Soc Lond Ser B Biol Sci. 2017;372(1732):pii: 20160274.

    Article  Google Scholar 

  48. Rohwer F, Youle M, Maughan H, Hisakawa N. Life in our phage world. A centennial field guide to the Earth’s most diverse inhabitants. San Diego: Wholon; 2014.

    Google Scholar 

  49. Scholtens PA, Oozeer R, Martin R, Amor KB, Knol J. The early settlers: intestinal microbiology in early life. Annu Rev Food Sci Technol. 2012;3:425–47.

    Article  CAS  Google Scholar 

  50. Seo YS, Shah VH. The role of gut-liver axis in the pathogenesis of liver cirrhosis and portal hypertension. Clin Mol Hepatol. 2012;18:337–46.

    Article  Google Scholar 

  51. Shukla SD, Budden KF, Neal R, Hansbro PM. Microbiome effects on immunity, health and disease in the lung. Clin Transl Immunoleogy. 2017;6:e133.

    Article  Google Scholar 

  52. Simmonds P, Adams MJ, Benko M, Breitbart M, Brister JR, Carstens EB, Davison AJ, Delwart E, Gorbalenya AE, Harrach B, Hull R, King AM, Koonin EV, Krupovic M, Kuhn JH, Lefkowitz EJ, Nibert ML, Orton R, Roossinck MJ, Sabanadzovic S, Sullivan MB, Suttle CA, Tesh RB, van der Vlugt RA, Varsani A, Zerbini FM. Consensus statement: virus taxonomy in the age of metagenomics. Nat Rev Microbiol. 2017;15:161–8.

    Article  CAS  Google Scholar 

  53. Singh RK, Chang HW, Yan D, Lee KM, Ucmak D, Wong K, Abrouk M, Farahnik B, Nakamura M, Zhu TH, Bhutani T, Liao W. Influence of diet on the gut microbiome and implications for human health. J Transl Med. 2017;15:73.

    Article  Google Scholar 

  54. Stremlau MH, Andersen KG, Folarin OA, Grove JN, Odia I, Ehiane PE, Omoniwa O, Omoregie O, Jiang PP, Yozwiak NL, Matranga CB, Yang X, Gire SK, Winnicki S, Tariyal R, Schaffner SF, Okokhere PO, Okogbenin S, Akpede GO, Asogun DA, Agbonlahor DE, Walker PJ, Tesh RB, Levin JZ, Garry RF, Sabeti PC, Happi CT. Discovery of novel rhabdoviruses in the blood of healthy individuals from West Africa. PLoS Negl Trop Dis. 2015;9:e0003631.

    Article  Google Scholar 

  55. Stulberg E, Fravel D, Proctor LM, Murray DM, LoTempio J, Chrisey L, Garland J, Goodwin K, Graber J, Harris MC, Jackson S, Mishkind M, Porterfield DM, Records A. An assessment of US microbiome research. Nat Microbiol. 2016;1:15015.

    Article  CAS  Google Scholar 

  56. Tremaroli V, Backhed F. Functional interactions between the gut microbiota and host metabolism. Nature. 2012;489:242–9.

    Article  CAS  Google Scholar 

  57. Van Belleghem JD, 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. 2017;7:8004.

    Article  Google Scholar 

  58. Virgin HW. The virome in mammalian physiology and disease. Cell. 2014;157:142–50.

    Article  CAS  Google Scholar 

  59. Virgin HW, Wherry EJ, Ahmed R. Redefining chronic viral infection. Cell. 2009;138:30–50.

    Article  CAS  Google Scholar 

  60. Wang FS, Fan JG, Zhang Z, Gao B, Wang HY. The global burden of liver disease: the major impact of China. Hepatology. 2014;60:2099–108.

    Article  Google Scholar 

  61. Weber-Dabrowska B, Dabrowski M, Slopek S. Studies on bacteriophage penetration in patients subjected to phage therapy. Arch Immunol Ther Exp. 1987;35:563–8.

    CAS  Google Scholar 

  62. Wedemeyer H, Manns MP. Epidemiology, pathogenesis and management of hepatitis D: update and challenges ahead. Nat Rev Gastroenterol Hepatol. 2010;7:31–40.

    Article  Google Scholar 

  63. Weinbauer MG. Ecology of prokaryotic viruses. FEMS Microbiol Rev. 2004;28:127–81.

    Article  CAS  Google Scholar 

  64. Yang JY, Kim MS, Kim E, Cheon JH, Lee YS, Kim Y, Lee SH, Seo SU, Shin SH, Choi SS, Kim B, Chang SY, Ko HJ, Bae JW, Kweon MN. Enteric viruses ameliorate gut inflammation via toll-like receptor 3 and toll-like receptor 7-mediated interferon-beta production. Immunity. 2016;44:889–900.

    Article  CAS  Google Scholar 

  65. Zhao G, Vatanen T, Droit L, Park A, Kostic AD, Poon TW, Vlamakis H, Siljander H, Harkonen T, Hamalainen AM, Peet A, Tillmann V, Ilonen J, Wang D, Knip M, Xavier RJ, Virgin HW. Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children. Proc Natl Acad Sci U S A. 2017;114:E6166–75.

    CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. KU Leuven, Department of Microbiology and Immunology, Rega Institute, Laboratory of Viral Metagenomics, Leuven, Belgium

    Jelle Matthijnssens & Shivaprasad Patil

  2. The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Emilie Glad Bak

  3. KU Leuven, Department of Microbiology and Immunology, Rega Institute, Laboratory of Clinical Virology, Leuven, Belgium

    Mahmoud Reza Pourkarim

  4. Polish Academy of Sciences, Hirszfeld Institute of Immunology and Experimental Therapy, Laboratory of Bacteriophages, Wrocław, Poland

    Andrzej Górski

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  1. Jelle Matthijnssens
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  2. Emilie Glad Bak
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  3. Shivaprasad Patil
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  4. Mahmoud Reza Pourkarim
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  5. Andrzej Górski
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Correspondence to Jelle Matthijnssens .

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  1. Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark

    Aleksander Krag

  2. The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Copenhagen, Denmark

    Torben Hansen

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Matthijnssens, J., Bak, E.G., Patil, S., Pourkarim, M.R., Górski, A. (2019). The Role of the Virome in the Gut-Liver Axis. In: Krag, A., Hansen, T. (eds) The Human Gut-Liver-Axis in Health and Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-98890-0_8

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