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Elevated plasma phage load as a marker for intestinal permeability in leukemic patients

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Abstract

Microbial translocation (MT) and altered gut microbiota have been described in acute leukemic patients and contribute to immune activation and inflammation. However, phage translocation has not been investigated in leukemia patients yet. We recruited 44 leukemic patients and 52 healthy adults and quantified the levels of 3 phages in peripheral blood, which were the most positive phages screened from fecal samples. The content of 16S rRNA in plasma was detected by qPCR to assess the intestinal mucosa of these patients. Spearman’s rank correlation was used to analyze the relationship between phage load and the relevant clinical data. We found the most prevalent phages in fecal samples were λ phage, Wphi phage, and P22 phage, and λ phage had the highest detection rate in plasma (68%). Phage content was affected by chemotherapy and course of disease and correlated with the levels of CRP (r = 0.43, p = 0.003), sCD14 (r = 0.37, p = 0.014), and sCD163 (r = 0.44, p = 0.003). Our data indicate that plasma phage load is a promising marker for gut barrier damage and that gut phage translocation correlates with monocyte/macrophage activation and systemic inflammatory response in leukemic patients.

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References

  1. Blum HE (2017) The human microbiome. Adv Med Sci 62(2):414–420

    Article  PubMed  Google Scholar 

  2. Clemente JC, Ursell LK, Parfrey LW, Knight R (2012) The impact of the gut microbiota on human health: an integrative view. Cell 148(6):1258–1270

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Fung TC, Olson CA, Hsiao EY (2017) Interactions between the microbiota, immune and nervous systems in health and disease. Nat Neurosci 20(2):145–155

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Hollister EB, Gao C, Versalovic J (2014) Compositional and functional features of the gastrointestinal microbiome and their effects on human health. Gastroenterology 146(6):1449–1458

    Article  PubMed  Google Scholar 

  5. Tetz G, Tetz V (2018) Bacteriophages as new human viral pathogens. Microorganisms 6(2):54

    Article  PubMed Central  CAS  Google Scholar 

  6. Chatterjee A, Duerkop BA (2018) Beyond bacteria: bacteriophage-eukaryotic host interactions reveal emerging paradigms of health and disease. Front Microbiol 9:1394

    Article  PubMed  PubMed Central  Google Scholar 

  7. Górski A, Wazna E, Dabrowska BW, Dabrowska K, Switała-Jeleń K, Miedzybrodzki R (2006) Bacteriophage translocation. FEMS Immunol Med Microbiol 46(3):313–319

    Article  PubMed  CAS  Google Scholar 

  8. Sinha A, Maurice CF (2019) Bacteriophages: uncharacterized and dynamic regulators of the immune system. Mediat Inflamm 2019:3730519

    Article  CAS  Google Scholar 

  9. Salmond GP, Fineran PC (2015) A century of the phage: past, present and future. Nat Rev Microbiol 13(12):777–786

    Article  PubMed  CAS  Google Scholar 

  10. Manrique P, Bolduc B, Walk ST, van der Oost J, de Vos WM, Young MJ (2016) Healthy human gut phageome. Proc Natl Acad Sci USA 113(37):10400–10405

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  11. Oh J, Byrd AL, Park M, Comparative Sequencing Program NISC, Kong HH, Segre JA (2016) Temporal stability of the human skin microbiome. Cell 165(4):854–866

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Miller-Ensminger T, Garretto A, Brenner J, Thomas-White K, Zambom A, Wolfe AJ, Putonti C (2018) Bacteriophages of the urinary microbiome. J Bacteriol 200(7):e00738–e817

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Lim ES, Zhou Y, Zhao G, Bauer IK, Droit L, Ndao IM, Warner BB, Tarr PI, Wang D, Holtz LR (2015) Early life dynamics of the human gut virome and bacterial microbiome in infants. Nat Med 21(10):1228–1234

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Reyes A, Blanton LV, Cao S, Zhao G, Manary M, Trehan I, Smith MI, Wang D, Virgin HW, Rohwer F, Gordon JI (2015) Gut DNA viromes of Malawian twins discordant for severe acute malnutrition. Proc Natl Acad Sci USA 112(38):11941–11946

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  15. Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, Magris M, Hidalgo G, Baldassano RN, Anokhin AP, Heath AC, Warner B, Reeder J, Kuczynski J, Caporaso JG, Lozupone CA, Lauber C, Clemente JC, Knights D, Knight R, Gordon JI (2012) Human gut microbiome viewed across age and geography. Nature 486(7402):222–227

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Reyes A, Haynes M, Hanson N, Angly FE, Heath AC, Rohwer F, Gordon JI (2010) Viruses in the faecal microbiota of monozygotic twins and their mothers. Nature 466(7304):334–338

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. De Sordi L, Khanna V, Debarbieux L (2017) The gut microbiota facilitates drifts in the genetic diversity and infectivity of bacterial viruses. Cell Host Microbe 22(6):801–808.e3

    Article  PubMed  CAS  Google Scholar 

  18. Modi SR, Lee HH, Spina CS, Collins JJ (2013) Antibiotic treatment expands the resistance reservoir and ecological network of the phage metagenome. Nature 499(7457):219–222

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Barr JJ (2019) Precision engineers: bacteriophages modulate the gut microbiome and metabolome. Cell Host Microbe 25(6):771–773

    Article  PubMed  CAS  Google Scholar 

  20. 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 (2015) Disease-specific alterations in the enteric virome in inflammatory bowel disease. Cell 160(3):447–460

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Tetz G, Brown SM, Hao Y, Tetz V (2018) Parkinson's disease and bacteriophages as its overlooked contributors. Sci Rep 8(1):10812

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Tetz G, Brown SM, Hao Y, Tetz V (2019) Type 1 diabetes: an association between autoimmunity, the dynamics of gut amyloid-producing E. coli and their phages. Sci Rep 9(1):9685

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Miernikiewicz P, Kłopot A, Soluch R, Szkuta P, Kęska W, Hodyra-Stefaniak K, Konopka A, Nowak M, Lecion D, Kaźmierczak Z, Majewska J, Harhala M, Górski A, Dąbrowska K (2016) T4 phage tail adhesin Gp12 counteracts LPS-induced inflammation in vivo. Front Microbiol 7:1112

    Article  PubMed  PubMed Central  Google Scholar 

  24. Ghose C, Ly M, Schwanemann LK, Shin JH, Atab K, Barr JJ, Little M, Schooley RT, Chopyk J, Pride DT (2019) The virome of cerebrospinal fluid: viruses where we once thought there were none. Front Microbiol 6(10):2061

    Article  Google Scholar 

  25. Tetz G, Tetz V (2016) Bacteriophage infections of microbiota can lead to leaky gut in an experimental rodent model. Gut Pathog 8:33

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Van Belleghem JD, Dąbrowska K, Vaneechoutte M, Barr JJ, Bollyky PL (2018) Interactions between bacteriophage, bacteria, and the mammalian immune system. Viruses 11(1):10

    Article  PubMed Central  CAS  Google Scholar 

  27. Dąbrowska K, Miernikiewicz P, Piotrowicz A, Hodyra K, Owczarek B, Lecion D, Kaźmierczak Z, Letarov A, Górski A (2014) Immunogenicity studies of proteins forming the T4 phage head surface. J Virol 88(21):12551–12557

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Gordon S (2002) Pattern recognition receptors: doubling up for the innate immune response. Cell 111(7):927–930

    Article  PubMed  CAS  Google Scholar 

  29. Gogokhia L, Buhrke K, Bell R, Hoffman B, Brown DG, Hanke-Gogokhia C, Ajami NJ, Wong MC, Ghazaryan A, Valentine JF, Porter N, Martens E, O'Connell R, Jacob V, Scherl E, Crawford C, Stephens WZ, Casjens SR, Longman RS, Round JL (2019) Expansion of bacteriophages is linked to aggravated intestinal inflammation and colitis. Cell Host Microbe 25(2):285–299.e8

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. De Paepe M, Leclerc M, Tinsley CR, Petit MA (2014) Bacteriophages: an underestimated role in human and animal health? Front Cell Infect Microbiol 4:39

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Duerkop BA, Hooper LV (2013) Resident viruses and their interactions with the immune system. Nat Immunol 14(7):654–659

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Ferreira RC, Guo H, Coulson RM, Smyth DJ, Pekalski ML, Burren OS, Cutler AJ, Doecke JD, Flint S, McKinney EF, Lyons PA, Smith KG, Achenbach P, Beyerlein A, Dunger DB, Clayton DG, Wicker LS, Todd JA, Bonifacio E, Wallace C, Ziegler AG (2014) A type I interferon transcriptional signature precedes autoimmunity in children genetically at risk for type 1 diabetes. Diabetes 63(7):2538–2550

    Article  PubMed  PubMed Central  Google Scholar 

  33. Rönnblom L, Alm G (2001) An etiopathogenic role for the type I IFN system in SLE. Trends Immunol 22(8):427–431

    Article  PubMed  Google Scholar 

  34. Juliusson G, Hough R (2016) Leukemia. Prog Tumor Res 43:87–100

    Article  PubMed  Google Scholar 

  35. Bow EJ, Meddings JB (2006) Intestinal mucosal dysfunction and infection during remission-induction therapy for acute myeloid leukaemia. Leukemia 20(12):2087–2092

    Article  PubMed  CAS  Google Scholar 

  36. Østgård LSG, Nørgaard M, Pedersen L, Østgård RD, Jensen MK (2018) Autoimmune diseases, infections, use of antibiotics and the risk of acute myeloid leukaemia: a national population-based case-control study. Br J Haematol 181(2):205–214

    Article  PubMed  CAS  Google Scholar 

  37. Meisel M, Hinterleitner R, Pacis A, Chen L, Earley ZM, Mayassi T, Pierre JF, Ernest JD, Galipeau HJ, Thuille N, Bouziat R, Buscarlet M, Ringus DL, Wang Y, Li Y, Dinh V, Kim SM, McDonald BD, Zurenski MA, Musch MW, Furtado GC, Lira SA, Baier G, Chang EB, Eren AM, Weber CR, Busque L, Godley LA, Verdú EF, Barreiro LB, Jabri B (2018) Microbial signals drive pre-leukaemic myeloproliferation in a Tet2-deficient host. Nature 557(7706):580–584

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Lin RS, Lee FY, Lee SD, Tsai YT, Lin HC, Lu RH, Hsu WC, Huang CC, Wang SS, Lo KJ (1995) Endotoxemia in patients with chronic liver diseases: relationship to severity of liver diseases, presence of esophageal varices, and hyperdynamic circulation. J Hepatol 22(2):165–172

    Article  PubMed  CAS  Google Scholar 

  39. Bigatello LM, Broitman SA, Fattori L, Di Paoli M, Pontello M, Bevilacqua G, Nespoli A (1987) Endotoxemia, encephalopathy, and mortality in cirrhotic patients. Am J Gastroenterol 82(1):11–15

    PubMed  CAS  Google Scholar 

  40. Such J, Francés R, Muñoz C, Zapater P, Casellas JA, Cifuentes A, Rodríguez-Valera F, Pascual S, Sola-Vera J, Carnicer F, Uceda F, Palazón JM, Pérez-Mateo M (2002) Detection and identification of bacterial DNA in patients with cirrhosis and culture-negative, nonneutrocytic ascites. Hepatology (Baltimore, MD) 36(1):135–141

    Article  CAS  Google Scholar 

  41. Alexopoulou A, Agiasotelli D, Vasilieva LE, Dourakis SP (2017) Bacterial translocation markers in liver cirrhosis. Ann gastroenterol 30(5):486–497

    PubMed  PubMed Central  Google Scholar 

  42. Lefkowitz EJ, Dempsey DM, Hendrickson RC, Orton RJ, Siddell SG, Smith DB (2018) Virus taxonomy: the database of the International Committee on Taxonomy of Viruses (ICTV). Nucl Acids Res 46(D1):D708–D717

    Article  PubMed  CAS  Google Scholar 

  43. Edelman DC, Barletta J (2003) Real-time PCR provides improved detection and titer determination of bacteriophage. Biotechniques 35(2):368–375

    Article  PubMed  CAS  Google Scholar 

  44. Liu T, Haggårdljungquist E (1999) The transcriptional switch of bacteriophage WPhi, a P2-related but heteroimmune coliphage. J Virol 73(12):9816

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Asija K, Teschke CM (2019) Of capsid structure and stability: the partnership between charged residues of E-loop and P-domain of the bacteriophage P22 coat protein. Virology 534:45–53

    Article  PubMed  CAS  Google Scholar 

  46. Miller ES, Jozwik CE (1990) Sequence analysis of conserved regA and variable orf43.1 genes in T4-like bacteriophages. J Bacteriol 172(9):5180–5186

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Li Y, Xie L, Xin S, Li K (2017) Values of procalcitonin and C-reactive proteins in the diagnosis and treatment of chronic obstructive pulmonary disease having concomitant bacterial infection. Pak J Med Sci 33(3):566

    PubMed  PubMed Central  Google Scholar 

  48. Hübner ST, Bertoli R, Bravo AER, Schaueblin M, Haschke M, Scherer K, Ceschi A, Leuppi-Taegtmeyer AB (2018) C-reactive protein and procalcitonin in case reports of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. Int Arch Allergy Immunol 176(1):44–54

    Article  PubMed  CAS  Google Scholar 

  49. Bafadhel M, Clark TW, Reid C, Medina M-j, Batham S, Barer MR, Nicholson KG, Brightling CE (2011) Procalcitonin and C-reactive protein in hospitalized adult patients with community-acquired pneumonia or exacerbation of asthma or COPD. Chest 139(6):1410–1418

    Article  PubMed  CAS  Google Scholar 

  50. Sulahian TH, Högger P, Wahner AE, Wardwell K, Goulding NJ, Sorg C, Droste A, Stehling M, Wallace PK, Morganelli PM, Guyre PM (2000) Human monocytes express CD163, which is upregulated by IL-10 and identical to p155. Cytokine 12(9):1312–1321

    Article  PubMed  CAS  Google Scholar 

  51. Wright SD, Ramos RA, Tobias PS, Ulevitch RJ, Mathison JC (1990) CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 249(4975):1431–1433

    Article  PubMed  CAS  Google Scholar 

  52. Nielsen MC, Andersen MN, Rittig N, Rødgaard-Hansen S, Grønbæk H, Moestrup SK, Møller HJ, Etzerodt A (2019) The macrophage-related biomarkers sCD163 and sCD206 are released by different shedding mechanisms. J Leukoc Biol 106(5):1129–1138

    Article  PubMed  CAS  Google Scholar 

  53. Burdo TH, Lo J, Abbara S, Wei J, DeLelys ME, Preffer F, Rosenberg ES, Williams KC, Grinspoon S (2011) Soluble CD163, a novel marker of activated macrophages, is elevated and associated with noncalcified coronary plaque in HIV-infected patients. J Infect Dis 204(8):1227–1236

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Breitbart M, Hewson I, Felts B, Mahaffy JM, Rohwer F (2003) Metagenomic analyses of an uncultured viral community from human feces. J Bacteriol 185(20):6220–6223

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Handley SA, Thackray LB, Zhao G, Presti R, Miller AD, Droit L, Abbink P, Maxfield LF, Kambal A, Duan E (2012) Pathogenic simian immunodeficiency virus infection is associated with expansion of the enteric virome. Cell 151(2):253–266

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. 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 (2017) Bacteriophage transcytosis provides a mechanism to cross epithelial cell layers. mBio 8(6):e01874–e1917

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Zhang L, Sun L, Wei R, Gao Q, He T, Xu C, Liu X, Wang R (2017) Intracellular Staphylococcus aureus control by virulent bacteriophages within MAC-T bovine mammary epithelial cells. Antimicrob Agents Chemother 61(2):e01990–e2016

    PubMed  PubMed Central  CAS  Google Scholar 

  58. Rashidi A, DeFor TE, Holtan SG, Blazar BR, Weisdorf DJ, MacMillan ML (2019) Outcomes and predictors of response in steroid-refractory acute graft-versus-host disease. Biol Blood Marrow Transpl 25(11):2297–2302

    Article  CAS  Google Scholar 

  59. Marchetti G, Tincati C, Silvestri G (2013) Microbial translocation in the pathogenesis of HIV infection and AIDS. Clin Microbiol Rev 26(1):2–18

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Ilan Y (2012) Leaky gut and the liver: a role for bacterial translocation in nonalcoholic steatohepatitis. World J Gastroenterol 18(21):2609

    Article  PubMed  PubMed Central  Google Scholar 

  61. Wallet MA, Rodriguez CA, Yin L, Saporta S, Chinratanapisit S, Hou W, Sleasman JW, Goodenow MM (2010) Microbial translocation induces persistent macrophage activation unrelated to HIV-1 levels or T-cell activation following therapy. Aids 24(9):1281–1290

    Article  PubMed  CAS  Google Scholar 

  62. Górski A, Międzybrodzki R, Borysowski J, Dąbrowska K, Kłosowska D (2012) Phage as a modulator of immune responses: practical implications for phage therapy. Adv Virus Res 83:41–71

    Article  PubMed  CAS  Google Scholar 

  63. Rhee I (2016) Diverse macrophages polarization in tumor microenvironment. Arch Pharm Res 39(11):1588–1596

    Article  PubMed  CAS  Google Scholar 

  64. Sun YX, Kong HL, Liu CF, Yu S, Tian T, Ma DX, Ji CY (2014) The imbalanced profile and clinical significance of T helper associated cytokines in bone marrow microenvironment of the patients with acute myeloid leukemia. Hum Immunol 75(2):113–118

    Article  PubMed  CAS  Google Scholar 

  65. Kunnumakkara AB, Sailo BL, Banik K, Harsha C, Prasad S, Gupta SC, Bharti AC, Aggarwal BB (2018) Chronic diseases, inflammation, and spices: how are they linked? J Transl Med 16(1):14

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Garcia C, Gardner D, Reichard KK (2008) CD163: a specific immunohistochemical marker for acute myeloid leukemia with monocytic differentiation. Appl Immunohistochem Mol Morphol 16(5):417–421

    Article  PubMed  CAS  Google Scholar 

  67. Lau SK, Chu PG, Weiss LM (2004) CD163A specific marker of macrophages in paraffin-embedded tissue samples. Am J Clin Pathol 122(5):794–801

    Article  PubMed  Google Scholar 

  68. Komohara Y, Niino D, Saito Y, Ohnishi K, Horlad H, Ohshima K, Takeya M (2013) Clinical significance of CD163+ tumor-associated macrophages in patients with adult T-cell leukemia/lymphoma. Cancer Sci 104(7):945–951

    Article  PubMed  CAS  PubMed Central  Google Scholar 

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Acknowledgements

We would like to thank the Second Affiliated Hospital of Wenzhou Medical University for providing the specimens of leukemia patients and healthy controls.

Funding

This work was supported by the Natural Science Foundation of Zhejiang Province, China under Grant No. LY18H200006; Science and Technology Planning Project of Zhejiang Province, China under Grant No. 2018C37067; and Science and Technology Planning Project of Wenzhou, Zhejiang, China under Grant No. Y20180108. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China

    Xue-rui Yin, Ping Liu, Xi Xu, Ying Xia, Kai-zhao Huang, Qiong-dan Wang, Mei-mei Lai & Xiao-qun Zheng

  2. Qilu Children’s Hospital of Shandong University, Jinan, 250000, China

    Ping Liu

  3. The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China

    Qiong-dan Wang

  4. Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Qi-gui Yu

  5. School of Laboratory Medicine and Life Sciences, The Key Laboratory of Laboratory Medicine, Ministry of Education of China, Wenzhou Medical University, University Town, Room 327, Tongren Building, Chashan, Wenzhou, 325000, Zhejiang, China

    Xiao-qun Zheng

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  1. Xue-rui Yin
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Contributions

XY, PL and XX carried out the experiments. XY, PL, KH and QW analyzed and discussed the data. XY, XX and YX searched the related literature and prepared the manuscript. XY wrote the manuscript; XY, ML and XZ edited the manuscript. QY and XZ conceived the study, ML and PL designed the study.

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Correspondence to Xiao-qun Zheng.

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Yin, Xr., Liu, P., Xu, X. et al. Elevated plasma phage load as a marker for intestinal permeability in leukemic patients. Med Microbiol Immunol 209, 693–703 (2020). https://doi.org/10.1007/s00430-020-00694-y

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