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.

The microbiome—the revealing of a long time unbeknownst factor for outcome in murine models of graft-versus-host disease

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    Zhang X, Li L, Butcher J, Stintzi A, Figeys D. Advancing functional and translational microbiome research using meta-omics approaches. Microbiome. 2019;7:154.

    PubMed  PubMed Central  Article  Google Scholar 

  2. 2.

    Vangay P, Johnson AJ, Ward TL, Al-Ghalith GA, Shields-Cutler RR, Hillmann BM, et al. US Immigration westernizes the human gut microbiome. Cell. 2018;175:962–72.e10.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  3. 3.

    Lynch SV, Pedersen O. The human intestinal microbiome in health and disease. N Engl J Med. 2016;375:2369–79.

    CAS  PubMed  Article  Google Scholar 

  4. 4.

    Clemente JC, Ursell LK, Parfrey LW, Knight R. The impact of the gut microbiota on human health: an integrative view. Cell. 2012;148:1258–70.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  5. 5.

    Eisenstein M. The hunt for a healthy microbiome. Nature 2020;577:S6–S8.

    CAS  PubMed  Article  Google Scholar 

  6. 6.

    Reddy PaF, JLM. Mouse models of graft-versus-host disease StemBook, ed: The Stem Cell Research Community, StemBook, 2009 February 2009.

  7. 7.

    Schroeder MA, DiPersio JF. Mouse models of graft-versus-host disease: advances and limitations. Dis Model Mech. 2011;4:318–33.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  8. 8.

    Peled J, Gomes A, Devlin S, Littmann E, Taur Y, Sung A, et al. Microbiota as predictor of mortality in allogeneic hematopoietic-cell transplantation. N Engl J Med. 2020;382:822–34.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  9. 9.

    Mathewson ND, Jenq R, Mathew AV, Koenigsknecht M, Hanash A, Toubai T, et al. Gut microbiome-derived metabolites modulate intestinal epithelial cell damage and mitigate graft-versus-host disease. Nat Immunol. 2016;17:505–13.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  10. 10.

    Wu K, Yuan Y, Yu H, Dai X, Wang S, Sun Z, et al. Gut microbial metabolite trimethylamine N-oxide aggravates GVHD by inducing M1 macrophage polarization in mice. Blood. 2020;136:501–15.

  11. 11.

    Stein-Thoeringer CK, Nichols KB, Lazrak A, Docampo MD, Slingerland AE, Slingerland JB, et al. Lactose drives enterococcus expansion to promote graft-versus-host disease. Science. 2019;366:1143–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  12. 12.

    Koyama M, Mukhopadhyay P, Schuster IS, Henden AS, Hulsdunker J, Varelias A, et al. MHC class II antigen presentation by the intestinal epithelium initiates graft-versus-host disease and is influenced by the microbiota. Immunity. 2019;51:885–98.e7.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  13. 13.

    Tichelli A, Gratwohl A. Vascular endothelium as ‘novel’ target of graft-versus-host disease. Best Pract Res Clin Haematol. 2008;21:139–48.

    CAS  PubMed  Article  Google Scholar 

  14. 14.

    Martinez-Sanchez J, Hamelmann H, Palomo M, Mir E, Moreno-Castaño AB, Torramade S, et al. Acute graft-vs.-host disease-associated endothelial activation in vitro is prevented by defibrotide. Front Immunol. 2019;10:2339.

  15. 15.

    Biedermann BC, Sahner S, Gregor M, Tsakiris DA, Jeanneret C, Pober JS, et al. Endothelial injury mediated by cytotoxic T lymphocytes and loss of microvessels in chronic graft versus host disease. Lancet. 2002;359:2078–83.

    PubMed  Article  Google Scholar 

  16. 16.

    Enaud R, Prevel R, Ciarlo E, Beaufils F, Wieërs G, Guery B, et al. The gut-lung axis in health and respiratory diseases: a place for inter-organ and inter-kingdom crosstalks. Front Cell Infect Microbiol. 2020;10:9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  17. 17.

    Kumari R, Palaniyandi S, Hildebrandt GC. Microbiome: an emerging new frontier in graft-versus-host disease. Digestive Dis Sci. 2019;64:669–77.

    Article  Google Scholar 

  18. 18.

    Kumari R, Palaniyandi S, Strattan E, Hildebrandt GC. Microbiome: an emerging new frontier in graft‑versus‑host disease. Inflamm Res. 2020;64:669–677.

  19. 19.

    Kobayashi T, Glatz M, Horiuchi K, Kawasaki H, Akiyama H, Kaplan DH, et al. Dysbiosis and staphylococcus aureus colonization drives inflammation in atopic dermatitis. Immunity 2015;42:756–66.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  20. 20.

    Santos E, Sousa P, Bennett CL, Chakraverty R. Unraveling the mechanisms of cutaneous graft-versus-host disease. Front Immunol. 2018;9:963.

    Article  CAS  Google Scholar 

  21. 21.

    Heintz-Buschart A, Wilmes P. Human gut microbiome: function matters. Trends Microbiol. 2018;26:563–74.

    CAS  PubMed  Article  Google Scholar 

  22. 22.

    Rinninella E, Raoul P, Cintoni M, Franceschi F, Miggiano GAD, Gasbarrini A, et al. What is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseases. microorganisms. 2019;7:14.

    CAS  Google Scholar 

  23. 23.

    Ruan W, Engevik MA, Spinler JK, Versalovic J. Healthy human gastrointestinal microbiome: composition and function after a decade of exploration. Digestive Dis Sci. 2020;65:695–705.

    CAS  Article  Google Scholar 

  24. 24.

    Cummings JH, Pomare EW, Branch WJ, Naylor CP, Macfarlane GT. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut 1987;28:1221–7.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  25. 25.

    Dalile B, Van Oudenhove L, Vervliet B, Verbeke K. The role of short-chain fatty acids in microbiota-gut-brain communication. Nat Rev Gastroenterol Hepatol. 2019;16:461–78.

  26. 26.

    Morrison DJ, Preston T. Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes. 2016;7:189–200.

    PubMed  PubMed Central  Article  Google Scholar 

  27. 27.

    Silva YP, Bernardi A, Frozza RL. The role of short-chain fatty acids from gut microbiota in gut-brain communication. Front. Endocrinol. 2020;11:25.

  28. 28.

    Shono Y, Docampo MD, Peled JU, Perobelli SM, Velardi E, Tsai JJ, et al. Increased GVHD-related mortality with broad-spectrum antibiotic use after allogeneic hematopoietic stem cell transplantation in human patients and mice. Sci Transl Med. 2016;8:339ra71.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  29. 29.

    Jenq RR, Taur Y, Devlin SM, Ponce DM, Goldberg JD, Ahr KF, et al. Intestinal Blautia Is Associated with Reduced Death from Graft-versus-Host Disease. Biol Blood Marrow Transplant. 2015;21:1373–83.

    PubMed  PubMed Central  Article  Google Scholar 

  30. 30.

    Peled JU, Gomes ALC. Microbiota as predictor of mortality in allogeneic hematopoietic-cell transplantation. N. Engl. J. Med. 2020;382:822–34.

  31. 31.

    Bowerman KL, Varelias A, Lachner N, Kuns RD, Hill GR, Hugenholtz P. Continuous pre- and post-transplant exposure to a disease-associated gut microbiome promotes hyper-acute graft-versus-host disease in wild-type mice. Gut Microbes. 2020;11:754–70.

  32. 32.

    Ingham AC, Kielsen K, Cilieborg MS, Lund O, Holmes S, Aarestrup FM, et al. Specific gut microbiome members are associated with distinct immune markers in pediatric allogeneic hematopoietic stem cell transplantation. Microbiome. 2019;7:131.

  33. 33.

    Weber D, Oefner PJ, Hiergeist A, Koestler J, Gessner A, Weber M, et al. Low urinary indoxyl sulfate levels early after transplantation reflect a disrupted microbiome and are associated with poor outcome. Blood. 2015;126:1723–8.

    CAS  PubMed  Article  Google Scholar 

  34. 34.

    Ilett EE, Jørgensen M, Noguera-Julian M, Nørgaard JC, Daugaard G, Helleberg M, et al. Associations of the gut microbiome and clinical factors with acute GVHD in allogeneic HSCT recipients. Blood Adv. 2020;4:5797–809.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  35. 35.

    Parth Gandhi IG, Andrea Hoeschen, Wes Mosher, Margaret L. MacMillan, Armin Rashidi, Najla H El Jurdi, et al. Plasma short chain fatty acids as a predictor of response to therapy for life-threatening acute graft-versus-host disease. Blood. 2020;136:14.

    Article  Google Scholar 

  36. 36.

    Harris B, Morjaria SM, Littmann ER, Geyer AI, Stover DE, Barker JN, et al. Gut microbiota predict pulmonary infiltrates after allogeneic hematopoietic cell transplantation. Am J respiratory Crit Care Med. 2016;194:450–63.

    CAS  Article  Google Scholar 

  37. 37.

    Amedei A, Morbidelli L. Circulating metabolites originating from gut microbiota control endothelial cell function. Molecules 2019;24:3992.

    CAS  PubMed Central  Article  PubMed  Google Scholar 

  38. 38.

    Schirbel A, Kessler S, Rieder F, West G, Rebert N, Asosingh K, et al. Pro-angiogenic activity of TLRs and NLRs: a novel link between gut microbiota and intestinal angiogenesis. Gastroenterology 2013;144:613–23.e9.

    CAS  PubMed  Article  Google Scholar 

  39. 39.

    Chou RH, Chen CY, Chen IC, Huang HL, Lu YW, Kuo CS, et al. Trimethylamine n-oxide, circulating endothelial progenitor cells, and endothelial function in patients with stable angina. Sci Rep. 2019;9:4249.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  40. 40.

    Bansal T, Alaniz RC, Wood TK, Jayaraman A. The bacterial signal indole increases epithelial-cell tight-junction resistance and attenuates indicators of inflammation. Proc Natl Acad Sci USA. 2010;107:228–33.

    CAS  PubMed  Article  Google Scholar 

  41. 41.

    Swimm A, Giver CR, DeFilipp Z, Rangaraju S, Sharma A. Indoles derived from intestinal microbiota act via type I interferon signaling to limit graft-versus-host disease. Blood. 2018;132:2506–19.

  42. 42.

    Zelante T, Iannitti RG, Cunha C, De Luca A, Giovannini G, Pieraccini G, et al. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity. 2013;39:372–85.

    CAS  PubMed  Article  Google Scholar 

  43. 43.

    Han L, Zhang H, Chen S, Zhou L, Li Y, Zhao K, et al. Intestinal microbiota can predict acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2019;25:1944–55.

    CAS  PubMed  Article  Google Scholar 

  44. 44.

    Hülsdünker J, Thomas OS, Haring E, Unger S, Gonzalo Núñez N, Tugues S, et al. Immunization against poly-N-acetylglucosamine reduces neutrophil activation and GVHD while sparing microbial diversity. Proc Natl Acad Sci USA. 2019;116:20700–6.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  45. 45.

    Fujiwara H, Docampo MD, Riwes M, Peltier D, Toubai T, Henig I, et al. Microbial metabolite sensor GPR43 controls severity of experimental GVHD. Nat Commun. 2018;9:3674.

  46. 46.

    Jankovic D, Ganesan J, Bscheider M, Stickel N, Weber FC, Guarda G, et al. The Nlrp3 inflammasome regulates acute graft-versus-host disease. J Exp Med. 2013;210:1899–910.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  47. 47.

    Dubois T, Tremblay YDN, Hamiot A, Martin-Verstraete I, Deschamps J, Monot M, et al. A microbiota-generated bile salt induces biofilm formation in Clostridium difficile. npj Biofilms Microbiomes. 2019;5:14.

    PubMed  PubMed Central  Article  Google Scholar 

  48. 48.

    Seekatz AM, Theriot CM, Rao K, Chang Y-M, Freeman AE, Kao JY, et al. Restoration of short chain fatty acid and bile acid metabolism following fecal microbiota transplantation in patients with recurrent Clostridium difficile infection. Anaerobe. 2018;53:64–73.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  49. 49.

    Toubai T, Fujiwara H, Rossi C, Riwes M, Tamaki H, Zajac C, et al. Host NLRP6 exacerbates graft-versus-host disease independent of gut microbial composition. Nat Microbiol. 2019;4:800–12.

  50. 50.

    Ward JM, Fox JG, Anver MR, Haines DC, George CV, Collins MJ Jr, et al. Chronic active hepatitis and associated liver tumors in mice caused by a persistent bacterial infection with a novel Helicobacter species. J Natl Cancer Inst. 1994;86:1222–7.

    CAS  PubMed  Article  Google Scholar 

  51. 51.

    Hailey JR, Haseman JK, Bucher JR, Radovsky AE, Malarkey DE, Miller RT, et al. Impact of Helicobacter hepaticus infection in B6C3F1 mice from twelve National Toxicology Program two-year carcinogenesis studies. Toxicol Pathol. 1998;26:602–11.

    CAS  PubMed  Article  Google Scholar 

  52. 52.

    Bassetti M, Bandera A, Gori A. Therapeutic potential of the gut microbiota in the management of sepsis. Crit Care. 2020;24:105.

    PubMed  PubMed Central  Article  Google Scholar 

  53. 53.

    Osbelt L, Thiemann S, Smit N, Lesker TR, Schröter M, Gálvez EJC, et al. Variations in microbiota composition of laboratory mice influence Citrobacter rodentium infection via variable short-chain fatty acid production. PLoS Pathog. 2020;16:e1008448.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  54. 54.

    Stolfi JL, Pai C-CS, Murphy WJ. Preclinical modeling of hematopoietic stem cell transplantation—advantages and limitations. FEBS J. 2016;283:1595–606.

    CAS  PubMed  Article  Google Scholar 

  55. 55.

    Blazar BR, Murphy WJ, Abedi M. Advances in graft-versus-host disease biology and therapy. Nat Rev Immunol. 2012;12:443–58.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  56. 56.

    Varelias A, Ormerod KL, Bunting MD, Koyama M, Gartlan KH, Kuns RD, et al. Acute graft-versus-host disease is regulated by an IL- 17-sensitive microbiome. Blood. 2017;129:2 17 2–85.

    CAS  Article  Google Scholar 

  57. 57.

    Docampo MD, Stein-Thoeringer C, Lazrak A, da Silva MB, van den Brink MRM. Expression of the butyrate/niacin receptor, GPR109a on T cells plays an important role in a mouse model of graft versus host disease. J Immunol. 2019;202:69.34–69.34.

    Google Scholar 

  58. 58.

    Rao AR, Quinones MP, Garavito E, Kalkonde Y, Jimenez F, Gibbons C, et al. CC Chemokine receptor 2 expression in donor cells serves an essential role in graft-versus-host-disease. J Immunol. 2003;171:4875–85.

    CAS  PubMed  Article  Google Scholar 

  59. 59.

    Betts B, Bastian D, Nguyen H, Heinrichs J, Wu Y, Veerapathran A, et al. Targeting JAK2 By gene knockout or pacritinib treatment reduces Gvhd and xenograft rejection by promoting induced treg differentiation. Blood.126;23:1874 (2015).

  60. 60.

    Toubai T, Guoqing H, Rossi C, Mathewson N, Oravecz-Wilson K, Cummings E, et al. Ikaros deficiency in host hematopoietic cells separates GVL from GVHD after experimental allogeneic hematopoietic cell transplantation. Oncoimmunology 2015;4:e1016699.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  61. 61.

    Gartlan KH, Bommiasamy H, Paz K, Wilkinson AN, Owen M, Reichenbach DK, et al. A critical role for donor-derived IL–22 in cutaneous chronic GVHD. Am J Transplant. 2018;18:810–20.

    CAS  PubMed  Article  Google Scholar 

  62. 62.

    Saha A, Taylor PA, Lees CJ, Panoskaltsis-Mortari A, Osborn MJ, Feser CJ, et al. Donor and host B7-H4 expression negatively regulates acute graft-versus-host disease lethality. JCI Insight. 2019;4:e127716.

  63. 63.

    Köhler N, Zeiser R. Intestinal microbiota influence immune tolerance post allogeneic hematopoietic cell transplantation and intestinal GVHD. Front Immunol. 2019;9:3179.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  64. 64.

    Lin C–H, Chen C–C, Chiang H–L, Liou J-M, Chang C–M, Lu T–P, et al. Altered gut microbiota and inflammatory cytokine responses in patients with Parkinson’s disease. J Neuroinflammation. 2019;16:129.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  65. 65.

    Li H-L, Lu L, Wang X-S, Qin L-Y, Wang P, Qiu S-P, et al. Alteration of gut microbiota and inflammatory cytokine/chemokine profiles in 5-fluorouracil induced intestinal mucositis. Front Cell Infect Microbiol. 2017;7:455.

  66. 66.

    Hyvärinen K, Koskela S, Niittyvuopio R, Nihtinen A, Volin L, Salmenniemi U, et al. Meta-analysis of genome-wide association and gene expression studies implicates donor t cell function and cytokine pathways in acute GvHD. Front Immunol. 2020;11:19.

  67. 67.

    Bowerman KL, Varelias A, Lachner N, Kuns RD, Hill GR, Hugenholtz P. Continuous pre- and post-transplant exposure to a disease-associated gut microbiome promotes hyper-acute graft-versus-host disease in wild-type mice. Gut Microbes. 2020:11:754–770.

  68. 68.

    Collins FS, Tabak LA. Policy: NIH plans to enhance reproducibility. Nature. 2014;505:612–3.

    PubMed  PubMed Central  Article  Google Scholar 

  69. 69.

    Perrin S. Preclinical research: Make mouse studies work. Nature. 2014;507:423–5.

    PubMed  Article  Google Scholar 

  70. 70.

    McCafferty J, Mühlbauer M, Gharaibeh RZ, Arthur JC, Perez-Chanona E, Sha W, et al. Stochastic changes over time and not founder effects drive cage effects in microbial community assembly in a mouse model. ISME J. 2013;7:2116–25.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  71. 71.

    Pritchett-Corning KR, Cosentino J, Clifford CB. Contemporary prevalence of infectious agents in laboratory mice and rats. Lab. Anim. 2009;43:165–73.

    CAS  PubMed  Article  Google Scholar 

  72. 72.

    Soave O, Brand CD. Coprophagy in animals: a review. Cornell Veterinarian. 1991;81:357–64.

    CAS  Google Scholar 

  73. 73.

    Benson AK, Kelly SA, Legge R, Ma F, Low SJ, Kim J, et al. Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors. Proc Natl Acad Sci USA. 2010;107:18933–8.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  74. 74.

    Ma BW, Bokulich NA, Castillo PA, Kananurak A, Underwood MA, Mills DA, et al. Routine habitat change: a source of unrecognized transient alteration of intestinal microbiota in laboratory mice. PLoS ONE. 2012;7:e47416.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  75. 75.

    Hildebrand F, Nguyen TL, Brinkman B, Yunta RG, Cauwe B, Vandenabeele P, et al. Inflammation-associated enterotypes, host genotype, cage and inter-individual effects drive gut microbiota variation in common laboratory mice. Genome Biol. 2013;14:R4.

    PubMed  PubMed Central  Article  Google Scholar 

  76. 76.

    Spor A, Koren O, Ley R. Unravelling the effects of the environment and host genotype on the gut microbiome. Nat Rev Microbiol. 2011;9:279–90.

    CAS  PubMed  Article  Google Scholar 

  77. 77.

    Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T, Karaoz U, et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell. 2009;139:485–98.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  78. 78.

    Ericsson AC, Davis JW, Spollen W, Bivens N, Givan S, Hagan CE, et al. Effects of vendor and genetic background on the composition of the fecal microbiota of inbred mice. PLoS ONE. 2015;10:e0116704.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  79. 79.

    Hufeldt MR, Nielsen DS, Vogensen FK, Midtvedt T, Hansen AK. Variation in the gut microbiota of laboratory mice is related to both genetic and environmental factors. Comp Med. 2010;60:336–47.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. 80.

    Ivanov II, Frutos Rde L, Manel N, Yoshinaga K, Rifkin DB, Sartor RB, et al. Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe. 2008;4:337–49.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  81. 81.

    Parker KD, Albeke SE, Gigley JP, Goldstein AM, Ward NL. Microbiome composition in both wild-type and disease model mice is heavily influenced by mouse facility. Front Microbiol. 2018;9:1598.

  82. 82.

    Nguyen TL, Vieira-Silva S, Liston A, Raes J. How informative is the mouse for human gut microbiota research ? Dis Model Mech. 2015;8:1–16.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  83. 83.

    Krych L, Hansen CH, Hansen AK, van den Berg FW, Nielsen DS. Quantitatively different, yet qualitatively alike: a meta-analysis of the mouse core gut microbiome with a view towards the human gut microbiome. PLoS ONE. 2013;8:e62578.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  84. 84.

    Peloquin JM, Nguyen DD. The microbiota and inflammatory bowel disease: insights from animal models. Anaerobe. 2013;24:102–6.

    CAS  PubMed  Article  Google Scholar 

  85. 85.

    Wirtz S, Neurath MF. Mouse models of inflammatory bowel disease. Adv drug Deliv Rev. 2007;59:1073–83.

    CAS  PubMed  Article  Google Scholar 

  86. 86.

    Turnbaugh PJ, Bäckhed F, Fulton L, Gordon JI. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe. 2008;3:213–23.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  87. 87.

    Turnbaugh PJ, Ridaura VK, Faith JJ, Rey FE, Knight R, Gordon JI. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med. 2009;1:6ra14.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  88. 88.

    Collins J, Auchtung JM, Schaefer L, Eaton KA, Britton RA. Humanized microbiota mice as a model of recurrent Clostridium difficile disease. Microbiome. 2015;3:35.

    PubMed  PubMed Central  Article  Google Scholar 

  89. 89.

    Park JC, Im S-H. Of men in mice: the development and application of a humanized gnotobiotic mouse model for microbiome therapeutics. Exp Mol Med. 2020;52:1383–96.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  90. 90.

    Walter J, Armet AM, Finlay BB, Shanahan F. Establishing or exaggerating causality for the gut microbiome: lessons from human microbiota-associated rodents. Cell 2020;180:221–32.

    CAS  PubMed  Article  Google Scholar 

  91. 91.

    Hugenholtz F, de Vos WM. Mouse models for human intestinal microbiota research : a critical evaluation. Cell Mol Life Sci. 2018;75:149–60.

    CAS  PubMed  Article  Google Scholar 

  92. 92.

    Peled JU, Gomes ALC, Devlin SM, Littmann ER, Taur Y, Sung AD, et al. Microbiota as predictor of mortality in allogeneic hematopoietic-cell transplantation. N. Engl J Med. 2020;382:822–34.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  93. 93.

    van Beurden YH, de Groot PF, van Nood E, Nieuwdorp M, Keller JJ, Goorhuis A. Complications, effectiveness, and long term follow-up of fecal microbiota transfer by nasoduodenal tube for treatment of recurrent Clostridium difficile infection. United European. Gastroenterol J. 2017;5:868–79.

    Google Scholar 

  94. 94.

    Zhang F, Yeoh YK, Zuo T, Cheng F, Tang W, Cheung K, et al. IDDF2019-ABS-0157 Fecal microbiota transplantations reconstitute gut fungal and viral microbiota in graft-versus-host disease. Gut. 2019;68:A92.

    Google Scholar 

  95. 95.

    Bogatyrev SR, Rolando JC, Ismagilov RF. Self-reinoculation with fecal flora changes microbiota density and composition leading to an altered bile-acid profile in the mouse small intestine. Microbiome. 2020;8:19.

    PubMed  PubMed Central  Article  Google Scholar 

  96. 96.

    Making the mouse gut microbiome more human-like. ScienceDaily. Retrieved August 25, 2020 from. California Institute of Technology; (2020, February).

  97. 97.

    Cekanaviciute E, Yoo BB, Runia TF, Debelius JW, Singh S, Nelson CA, et al. Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. Proc Natl Acad Sci USA. 2017;114:10713.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  98. 98.

    Atarashi K, Tanoue T, Ando M, Kamada N, Nagano Y, Narushima S, et al. Th17 Cell induction by adhesion of microbes to intestinal epithelial cells. Cell. 2015;163:367–80.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  99. 99.

    Ingham AC, Kielsen K, Cilieborg MS, Lund O, Holmes S, Aarestrup FM, et al. Specific gut microbiome members are associated with distinct immune markers in pediatric allogeneic hematopoietic stem cell transplantation. Microbiome. 2019;7:131.

    PubMed  PubMed Central  Article  Google Scholar 

  100. 100.

    Han L, Jin H, Zhou L, Zhang X, Fan Z, Dai M, et al. Intestinal Microbiota at Engraftment Influence Acute Graft-Versus-Host Disease via the Treg/Th17 Balance in Allo-HSCT Recipients. Front Immunol. 2018;9:669.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  101. 101.

    Akaza H. Prostate cancer chemoprevention by soy isoflavones: role of intestinal bacteria as the “second human genome”. Cancer Sci. 2012;103:969–75.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  102. 102.

    Degen GH, Janning P, Diel P, Bolt HM. Estrogenic isoflavones in rodent diets. Toxicol Lett. 2002;128:145–57.

    CAS  PubMed  Article  Google Scholar 

  103. 103.

    Menon R, Watson SE, Thomas LN, Allred CD, Dabney A, Azcarate-Peril MA, et al. Diet complexity and estrogen receptor β status affect the composition of the murine intestinal microbiota. Appl Environ Microbiol. 2013;79:5763–73.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  104. 104.

    Cotillard A, Kennedy SP, Kong LC, Prifti E, Pons N, Le Chatelier E, et al. Dietary intervention impact on gut microbial gene richness. Nature. 2013;500:585–8.

    CAS  PubMed  Article  Google Scholar 

  105. 105.

    Maurice CF, Haiser HJ, Turnbaugh PJ. Xenobiotics shape the physiology and gene expression of the active human gut microbiome. Cell. 2013;152:39–50.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  106. 106.

    Romick-Rosendale LE, Haslam DB, Lane A, Denson L, Lake K, Wilkey A, et al. Antibiotic exposure and reduced short chain fatty acid production after hematopoietic stem cell transplant. Biol Blood Marrow Transplant. 2018;24:2418–24.

    CAS  PubMed  Article  Google Scholar 

  107. 107.

    Jenq RR, Ubeda C, Taur Y, Menezes CC, Khanin R, Dudakov JA, et al. Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation. J Exp Med. 2012;209:903–11.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  108. 108.

    Jenq RR, Taur Y, Devlin SM, Ponce DM, Goldberg JD, Ahr KF, et al. Intestinal blautia is associated with reduced death from graft-versus-host disease. Biol Blood Marrow Transplant. 2015;21:1373–83.

    PubMed  PubMed Central  Article  Google Scholar 

  109. 109.

    Holler E, Butzhammer P, Schmid K, Hundsrucker C, Koestler J, Peter K, et al. Metagenomic analysis of the stool microbiome in patients receiving allogeneic stem cell transplantation: loss of diversity is associated with use of systemic antibiotics and more pronounced in gastrointestinal graft-versus-host disease. Biol Blood Marrow Transplant. 2014;20:640–5.

    PubMed  PubMed Central  Article  Google Scholar 

  110. 110.

    Taur Y, Jenq RR, Perales MA, Littmann ER, Morjaria S, Ling L, et al. The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation. Blood. 2014;124:1174–82.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  111. 111.

    Simms-Waldrip TR, Sunkersett G, Coughlin LA, Savani MR, Arana C, Kim J, et al. Antibiotic-induced depletion of anti-inflammatory clostridia is associated with the development of graft-versus-host disease in pediatric stem cell transplantation patients. Biol Blood Marrow Transplant. 2017;23:820–9.

    CAS  PubMed  Article  Google Scholar 

  112. 112.

    Allaband C, McDonald D, Vázquez-Baeza Y, Minich JJ, Tripathi A, Brenner DA, et al. Microbiome 101: studying, analyzing, and interpreting gut microbiome data for clinicians. Clin Gastroenterol Hepatol. 2019;17:218–30.

    PubMed  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Gerhard Carl Hildebrandt.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

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

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kumari, R., Palaniyandi, S. & Hildebrandt, G.C. The microbiome—the revealing of a long time unbeknownst factor for outcome in murine models of graft-versus-host disease. Bone Marrow Transplant 56, 1777–1783 (2021). https://doi.org/10.1038/s41409-021-01325-7

Download citation

Search

Quick links