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  • Review Article
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Gut microbiota injury in allogeneic haematopoietic stem cell transplantation

Nature Reviews Cancer volume 18, pages 283–295 (2018)Cite this article

Subjects

Key Points

  • Allogeneic haematopoietic stem cell transplantation (allo-HSCT) offers the strongest anticancer therapy for many malignancies but has limited application owing to complications including graft-versus-host disease (GVHD), infections and relapse. Understanding the microbiota ecology in these settings will help to develop better strategies to overcome these complications.

  • Recent advances in large-scale DNA sequencing technology enable thorough evaluation of changes in microbiota in patients undergoing allo-HSCT, and evidence is starting to accumulate with regard to beneficial and harmful changes in microbiota in the setting of allo-HSCT.

  • Loss of microbiota diversity after allo-HSCT is associated with worse GVHD and mortality after allo-HSCT.

  • Faecal microbiota transfer (FMT) may be beneficial to restore a microbiota that has been injured. It potentially improves GVHD and prevents infectious complications after allo-HSCT.

  • Broad-spectrum antibiotic use can lead to microbiota injury and increases GVHD-related mortality after allo-HSCT.

  • To develop novel strategies to improve outcomes following allo-HSCT, better characterization of the changes in the microbiota after allo-HSCT should be performed in a prospective multicentre fashion.

Abstract

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is considered to be the strongest curative immunotherapy for various malignancies (primarily, but not limited to, haematologic malignancies). However, application of allo-HSCT is limited owing to its life-threatening major complications, such as graft-versus-host disease (GVHD), relapse and infections. Recent advances in large-scale DNA sequencing technology have facilitated rapid identification of the microorganisms that make up the microbiota and evaluation of their interactions with host immunity in various diseases, including cancer. This has resulted in renewed interest regarding the role of the intestinal flora in patients with haematopoietic malignancies who have received an allo-HSCT and in whether the microbiota affects clinical outcomes, including GVHD, relapse, infections and transplant-related mortality. In this Review, we discuss the potential role of intestinal microbiota in these major complications after allo-HSCT, summarize clinical trials evaluating the microbiota in patients who have received allo-HSCT and discuss how further studies of the microbiota could inform the development of strategies that improve outcomes of allo-HSCT.

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Figure 1: Allo-HSCT and GVHD.
Figure 2: Intestinal microbiota injury after allo-HSCT.
Figure 3: Studies on microbiota injuries in allo-HSCT recipients.
Figure 4: The interplay between gut microbiota and host physiology and immunity.
Figure 5: Microbiota injury and complications after allo-HSCT.

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References

  1. Jenq, R. R. & van den Brink, M. R. Allogeneic haematopoietic stem cell transplantation: individualized stem cell and immune therapy of cancer. Nature reviews. Cancer 10, 213–221 (2010).

    CAS  PubMed  Google Scholar 

  2. Zeiser, R. & Blazar, B. R. Acute graft-versus-host disease — biologic process, prevention, and therapy. N. Engl. J. Med. 377, 2167–2179 (2017). This is a detailed review of the current advances in the pathophysiology of GVHD and its treatment.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Shono, Y. et al. Bone marrow graft-versus-host disease: early destruction of hematopoietic niche after MHC-mismatched hematopoietic stem cell transplantation. Blood 115, 5401–5411 (2010).

    Article  CAS  PubMed  Google Scholar 

  4. Kamble, R. T., Chang, C. C., Sanchez, S. & Carrum, G. Central nervous system graft-versus-host disease: report of two cases and literature review. Bone Marrow Transplant. 39, 49–52 (2007).

    Article  CAS  PubMed  Google Scholar 

  5. Hartrampf, S. et al. The central nervous system is a target of acute graft versus host disease in mice. Blood 121, 1906–1910 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Shimoji, S. et al. Graft-versus-host disease targets ovary and causes female infertility in mice. Blood 129, 1216–1225 (2017).

    Article  CAS  PubMed  Google Scholar 

  7. Holler, E. 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. 20, 640–645 (2014). This study provides serial stool specimen analyses of 31 patients after allo-HSCT and shows loss of diversity and expansion of Enterococcus spp. in patients with GVHD.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Bhatt, A. S. et al. Sequence-based discovery of Bradyrhizobium enterica in cord colitis syndrome. N. Engl. J. Med. 369, 517–528 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Jones, J. M., Wilson, R. & Bealmear, P. M. Mortality and gross pathology of secondary disease in germfree mouse radiation chimeras. Radiat. Res. 45, 577–588 (1971).

    Article  CAS  PubMed  Google Scholar 

  10. van Bekkum, D. W., Roodenburg, J., Heidt, P. J. & van der Waaij, D. Mitigation of secondary disease of allogeneic mouse radiation chimeras by modification of the intestinal microflora. J. Natl Cancer Institute. 52, 401–404 (1974). This is an early mouse study showing that germ-free conditions or gut decontamination with antibiotics reduce mortality from GVHD.

    Article  CAS  Google Scholar 

  11. Storb, R. et al. Graft-versus-host disease and survival in patients with aplastic anemia treated by marrow grafts from HLA-identical siblings. Beneficial effect of a protective environment. N. Engl. J. Med. 308, 302–307 (1983).

    Article  CAS  PubMed  Google Scholar 

  12. Eriguchi, Y. et al. Graft-versus-host disease disrupts intestinal microbial ecology by inhibiting Paneth cell production of alpha-defensins. Blood 120, 223–231 (2012).

    Article  CAS  PubMed  Google Scholar 

  13. Jenq, R. R. et al. Intestinal Blautia is associated with reduced death from graft-versus-host disease. Biol. Blood Marrow Transplant. 21, 1373–1383 (2015). A clinical study evaluating stool specimens of 64 patients (at day 12 after allo-HSCT) showing that Blautia (Clostridial species) is associated with less GVHD-related mortality.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Jenq, R. R. et al. Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation. J. Exp. Med. 209, 903–911 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Shono, Y. 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. 8, 339ra71 (2016). This study shows that broad-spectrum antibiotic use is associated with increased GVHD-related mortality after allo-HSCT in both mice and humans.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Peled, J. U. et al. Intestinal microbiota and relapse after hematopoietic-cell transplantation. J. Clin. Oncol. 35, 1650–1659 (2017). This is the first study showing the association between relapse and microbiota after allo-HSCT, demonstrating an inverse relationship between the abundance of Eubacterium limosum and relapse in the first 3 weeks after transplant.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Roy, S. & Trinchieri, G. Microbiota: a key orchestrator of cancer therapy. Nat. Rev Cancer 17, 271–285 (2017). This is a review detailing the role of the microbiota in modulating chemotherapy, radiotherapy and immunotherapy.

    Article  CAS  PubMed  Google Scholar 

  18. Eckburg, P. B. et al. Diversity of the human intestinal microbial flora. Science 308, 1635–1638 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  19. Taur, Y. et al. Intestinal domination and the risk of bacteremia in patients undergoing allogeneic hematopoietic stem cell transplantation. Clin. Infect. Dis. 55, 905–914 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Taur, Y., Jenq, R. R., Ubeda, C., van den Brink, M. & Pamer, E. G. Role of intestinal microbiota in transplantation outcomes. Best Pract. Res. Clin. Haematol. 28, 155–161 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Shono, Y., Docampo, M. D., Peled, J. U., Perobelli, S. M. & Jenq, R. R. Intestinal microbiota-related effects on graft-versus-host disease. Int. J. Hematol. 101, 428–437 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Kyle, U. G. et al. Longitudinal follow-up of body composition in hematopoietic stem cell transplant patients. Bone Marrow Transplant. 35, 1171–1177 (2005).

    Article  CAS  PubMed  Google Scholar 

  23. Papadopoulou, A., Lloyd, D. R., Williams, M. D., Darbyshire, P. J. & Booth, I. W. Gastrointestinal and nutritional sequelae of bone marrow transplantation. Arch. Dis. Childhood. 75, 208–213 (1996).

    Article  CAS  Google Scholar 

  24. Taur, Y. et al. The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation. Blood 124, 1174–1182 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Human Microbiome Project, C. Structure, function and diversity of the healthy human microbiome. Nature 486, 207–214 (2012).

    Article  CAS  Google Scholar 

  27. Ubeda, C. et al. Vancomycin-resistant Enterococcus domination of intestinal microbiota is enabled by antibiotic treatment in mice and precedes bloodstream invasion in humans. J. Clin. Invest. 120, 4332–4341 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Harris, B. et al. Gut microbiota predict pulmonary infiltrates after allogeneic hematopoietic cell transplantation. Am. J. Respir. Crit. Care Med. 194, 450–463 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Alonso, C. D. & Marr, K. A. Clostridium difficile infection among hematopoietic stem cell transplant recipients: beyond colitis. Curr. Opin. Infect. Dis. 26, 326–331 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Willems, L. et al. Clostridium difficile infection after allogeneic hematopoietic stem cell transplantation: incidence, risk factors, and outcome. Biol. Blood Marrow Transplant. 18, 1295–1301 (2012).

    Article  PubMed  Google Scholar 

  31. Kinnebrew, M. A. et al. Early Clostridium difficile infection during allogeneic hematopoietic stem cell transplantation. PloS ONE 9, e90158 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Buffie, C. G. et al. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature 517, 205–208 (2015).

    Article  CAS  PubMed  Google Scholar 

  33. Andermann, T. M., Rezvani, A. & Bhatt, A. S. Microbiota manipulation with prebiotics and probiotics in patients undergoing stem cell transplantation. Curr. Hematol. Malig. Rep. 11, 19–28 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  34. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/study/NCT02269150 (2017).

  35. Quera, R., Espinoza, R., Estay, C. & Rivera, D. Bacteremia as an adverse event of fecal microbiota transplantation in a patient with Crohn's disease and recurrent Clostridium difficile infection. J. Crohns Colitis. 8, 252–253 (2014).

    Article  PubMed  Google Scholar 

  36. Schwartz, M., Gluck, M. & Koon, S. Norovirus gastroenteritis after fecal microbiota transplantation for treatment of Clostridium difficile infection despite asymptomatic donors and lack of sick contacts. Am. J. Gastroenterol. 108, 1367 (2013).

    Article  PubMed  Google Scholar 

  37. Chang, B. W. & Rezaie, A. Irritable bowel syndrome-like symptoms following fecal microbiota transplantation: a possible donor-dependent complication. Am. J. Gastroenterol. 112, 186–187 (2017).

    Article  PubMed  Google Scholar 

  38. Antin, J. H. & Ferrara, J. L. Cytokine dysregulation and acute graft-versus-host disease. Blood 80, 2964–2968 (1992).

    Article  CAS  PubMed  Google Scholar 

  39. Hill, G. R. & Ferrara, J. L. The primacy of the gastrointestinal tract as a target organ of acute graft-versus-host disease: rationale for the use of cytokine shields in allogeneic bone marrow transplantation. Blood 95, 2754–2759 (2000).

    Article  CAS  PubMed  Google Scholar 

  40. Thaiss, C. A., Zmora, N., Levy, M. & Elinav, E. The microbiome and innate immunity. Nature 535, 65–74 (2016).

    Article  CAS  PubMed  Google Scholar 

  41. Murphy, S. & Nguyen, V. H. Role of gut microbiota in graft-versus-host disease. Leuk. Lymphoma. 52, 1844–1856 (2011).

    Article  CAS  PubMed  Google Scholar 

  42. Mathewson, N. & Reddy, P. The microbiome and graft versus host disease. Curr. Stem Cell Rep. 1, 39–47 (2015).

    Article  CAS  Google Scholar 

  43. Heidegger, S., van den Brink, M. R., Haas, T. & Poeck, H. The role of pattern-recognition receptors in graft-versus-host disease and graft-versus-leukemia after allogeneic stem cell transplantation. Front. Immunol. 5, 337 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Wang, W., Xu, S., Ren, Z., Jiang, J. & Zheng, S. Gut microbiota and allogeneic transplantation. J. Transl Med. 13, 275 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Sonnenberg, G. F. & Artis, D. Innate lymphoid cell interactions with microbiota: implications for intestinal health and disease. Immunity 37, 601–610 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Hanash, A. M. et al. Interleukin-22 protects intestinal stem cells from immune-mediated tissue damage and regulates sensitivity to graft versus host disease. Immunity 37, 339–350 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Chen, Y., Zhao, Y., Cheng, Q., Wu, D. & Liu, H. The role of intestinal microbiota in acute graft-versus-host disease. J. Immunol. Res. 2015, 145859 (2015).

    PubMed  PubMed Central  Google Scholar 

  48. Zeiser, R., Socie, G. & Blazar, B. R. Pathogenesis of acute graft-versus-host disease: from intestinal microbiota alterations to donor T cell activation. Br. J. Haematol. 175, 191–207 (2016).

    Article  CAS  PubMed  Google Scholar 

  49. Whangbo, J., Ritz, J. & Bhatt, A. Antibiotic-mediated modification of the intestinal microbiome in allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 52, 183–190 (2017). This is a review that extensively explores previous studies on gut decontamination for acute GVHD prevention.

    Article  CAS  PubMed  Google Scholar 

  50. Zama, D. et al. Gut microbiota and hematopoietic stem cell transplantation: where do we stand? Bone Marrow Transplant. 52, 7–14 (2017).

    Article  CAS  PubMed  Google Scholar 

  51. Staffas, A., Burgos da Silva, M. & van den Brink, M. R. The intestinal microbiota in allogeneic hematopoietic cell transplant and graft-versus-host disease. Blood 129, 927–933 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Peled, J. U., Hanash, A. M. & Jenq, R. R. Role of the intestinal mucosa in acute gastrointestinal GVHD. Blood 128, 2395–2402 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Ferrara, J. L., Smith, C. M., Sheets, J., Reddy, P. & Serody, J. S. Altered homeostatic regulation of innate and adaptive immunity in lower gastrointestinal tract GVHD pathogenesis. J. Clin. Invest. 127, 2441–2451 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  54. Macpherson, A. J., Slack, E., Geuking, M. B. & McCoy, K. D. The mucosal firewalls against commensal intestinal microbes. Semin. Immunopathol. 31, 145–149 (2009).

    Article  PubMed  Google Scholar 

  55. Kaiko, G. E. et al. The colonic crypt protects stem cells from microbiota-derived metabolites. Cell 165, 1708–1720 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Peterson, L. W. & Artis, D. Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nat. Rev. Immunol. 14, 141–153 (2014).

    Article  CAS  PubMed  Google Scholar 

  57. Levine, J. E. et al. Low Paneth cell numbers at onset of gastrointestinal graft-versus-host disease identify patients at high risk for nonrelapse mortality. Blood 122, 1505–1509 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Sato, T. et al. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 469, 415–418 (2011).

    Article  CAS  PubMed  Google Scholar 

  59. Lindemans, C. A. et al. Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration. Nature 528, 560–564 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Qiu, J. et al. The aryl hydrocarbon receptor regulates gut immunity through modulation of innate lymphoid cells. Immunity 36, 92–104 (2012).

    Article  CAS  PubMed  Google Scholar 

  61. Zelante, T. et al. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity 39, 372–385 (2013).

    Article  CAS  PubMed  Google Scholar 

  62. Ferrara, J. L. et al. Regenerating islet-derived 3-alpha is a biomarker of gastrointestinal graft-versus-host disease. Blood 118, 6702–6708 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Brandl, K. et al. Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits. Nature 455, 804–807 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Zenewicz, L. A. et al. IL-22 deficiency alters colonic microbiota to be transmissible and colitogenic. J. Immunol. 190, 5306–5312 (2013).

    Article  CAS  PubMed  Google Scholar 

  65. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/study/NCT02406651 (2015).

  66. Hayase, E. et al. R-Spondin1 expands Paneth cells and prevents dysbiosis induced by graft-versus-host disease. J. Exp. Med. 214, 3507–3518 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Heimesaat, M. M. et al. MyD88/TLR9 mediated immunopathology and gut microbiota dynamics in a novel murine model of intestinal graft-versus-host disease. Gut 59, 1079–1087 (2010).

    Article  CAS  PubMed  Google Scholar 

  68. Steck, N. et al. Enterococcus faecalis metalloprotease compromises epithelial barrier and contributes to intestinal inflammation. Gastroenterology 141, 959–971 (2011).

    Article  CAS  PubMed  Google Scholar 

  69. Kim, S. O., Sheikh, H. I., Ha, S. D., Martins, A. & Reid, G. G-CSF-mediated inhibition of JNK is a key mechanism for Lactobacillus rhamnosus-induced suppression of TNF production in macrophages. Cell. Microbiol. 8, 1958–1971 (2006).

    Article  CAS  PubMed  Google Scholar 

  70. Atarashi, K. et al. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 500, 232–236 (2013).

    Article  CAS  PubMed  Google Scholar 

  71. Tanoue, T. & Honda, K. Induction of Treg cells in the mouse colonic mucosa: a central mechanism to maintain host-microbiota homeostasis. Semin. Immunol. 24, 50–57 (2012).

    Article  CAS  PubMed  Google Scholar 

  72. Narushima, S. et al. Characterization of the 17 strains of regulatory T cell-inducing human-derived Clostridia. Gut Microbes. 5, 333–339 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  73. Arpaia, N. et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504, 451–455 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Furusawa, Y. et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504, 446–450 (2013).

    Article  CAS  PubMed  Google Scholar 

  75. Mathewson, N. D. et al. Gut microbiome-derived metabolites modulate intestinal epithelial cell damage and mitigate graft-versus-host disease. Nat. Immunol. 17, 505–513 (2016). This study describes the role of butyrate in maintaining the integrity of IEC junctions that are impaired by GVHD.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Varelias, A. et al. Acute graft-versus-host disease is regulated by an IL-17-sensitive microbiome. Blood 129, 2172–2185 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Laterza, L., Rizzatti, G., Gaetani, E., Chiusolo, P. & Gasbarrini, A. The gut microbiota and immune system relationship in human graft-versus-host disease. Mediterr. J. Hematol. Infect. Dis. 8, e2016025 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  78. Chiusolo, P. et al. Gut microbiome changes after stem cell transplantation. Blood 126, 1953 (2015).

    Article  Google Scholar 

  79. Tawara, I. et al. Influence of donor microbiota on the severity of experimental graft-versus-host-disease. Biol. Blood Marrow Transplant. 19, 164–168 (2013).

    Article  PubMed  Google Scholar 

  80. Beelen, D. W., Elmaagacli, A., Muller, K. D., Hirche, H. & Schaefer, U. W. Influence of intestinal bacterial decontamination using metronidazole and ciprofloxacin or ciprofloxacin alone on the development of acute graft-versus-host disease after marrow transplantation in patients with hematologic malignancies: final results and long-term follow-up of an open-label prospective randomized trial. Blood 93, 3267–3275 (1999). This is a prospective randomized trial from Germany ( n = 134) indicating that the elimination of anaerobes with the addition of metronidazole to ciprofloxacin results in reduced grade II–IV GVHD.

    Article  CAS  PubMed  Google Scholar 

  81. Petersen, F. B. et al. Infectious complications in patients undergoing marrow transplantation: a prospective randomized study of the additional effect of decontamination and laminar air flow isolation among patients receiving prophylactic systemic antibiotics. Scand. J. Infect. Dis. 19, 559–567 (1987).

    Article  CAS  PubMed  Google Scholar 

  82. Passweg, J. R. et al. Influence of protective isolation on outcome of allogeneic bone marrow transplantation for leukemia. Bone Marrow Transplant. 21, 1231–1238 (1998).

    Article  CAS  PubMed  Google Scholar 

  83. Russell, J. A. et al. Early outcomes after allogeneic stem cell transplantation for leukemia and myelodysplasia without protective isolation: a 10-year experience. Biol. Blood Marrow Transplant. 6, 109–114 (2000).

    Article  CAS  PubMed  Google Scholar 

  84. Simms-Waldrip, T. R. 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. 23, 820–829 (2017).

    Article  CAS  PubMed  Google Scholar 

  85. Routy, B. et al. The influence of gut-decontamination prophylactic antibiotics on acute graft-versus-host disease and survival following allogeneic hematopoietic stem cell transplantation. Oncoimmunology 6, e1258506 (2017).

    Article  PubMed  CAS  Google Scholar 

  86. Vossen, J. M. et al. Complete suppression of the gut microbiome prevents acute graft-versus-host disease following allogeneic bone marrow transplantation. PloS ONE 9, e105706 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  87. Bilinski, J. et al. Impact of gut colonization by antibiotic-resistant bacteria on the outcomes of allogeneic hematopoietic stem cell transplantation: a retrospective, single-center study. Biol. Blood Marrow Transplant. 22, 1087–1093 (2016).

    Article  PubMed  Google Scholar 

  88. Perez-Simon, J. A. et al. Antibiotic prophylaxis with meropenem after allogeneic stem cell transplantation. Bone Marrow Transplant. 33, 183–187 (2004).

    Article  CAS  PubMed  Google Scholar 

  89. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/study/NCT03078010 (2017).

  90. Khoruts, A. et al. Toward revision of antimicrobial therapies in hematopoietic stem cell transplantation: target the pathogens, but protect the indigenous microbiota. Transl Res. 179, 116–125 (2017).

    Article  CAS  PubMed  Google Scholar 

  91. Weber, D. et al. Microbiota disruption induced by early use of broad-spectrum antibiotics is an independent risk factor of outcome after allogeneic stem cell transplantation. Biol. Blood Marrow Transplant. 23, 845–852 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Bucaneve, G. et al. Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia. N. Engl. J. Med. 353, 977–987 (2005).

    Article  CAS  PubMed  Google Scholar 

  93. Cullen, M. et al. Antibacterial prophylaxis after chemotherapy for solid tumors and lymphomas. N. Engl. J. Med. 353, 988–998 (2005).

    Article  CAS  PubMed  Google Scholar 

  94. Leibovici, L. et al. Antibiotic prophylaxis in neutropenic patients: new evidence, practical decisions. Cancer 107, 1743–1751 (2006).

    Article  CAS  PubMed  Google Scholar 

  95. Reuter, S. et al. Impact of fluoroquinolone prophylaxis on reduced infection-related mortality among patients with neutropenia and hematologic malignancies. Clin. Infect. Dis. 40, 1087–1093 (2005).

    Article  CAS  PubMed  Google Scholar 

  96. Freifeld, A. G. et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin. Infect. Dis. 52, e56–e93 (2011).

    Article  PubMed  Google Scholar 

  97. Satlin, M. J. et al. Impact of prophylactic levofloxacin on rates of bloodstream infection and fever in neutropenic patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation. Biol. Blood Marrow Transplant. 21, 1808–1814 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Lopetuso, L. R., Petito, V., Scaldaferri, F. & Gasbarrini, A. Gut microbiota modulation and mucosal immunity: focus on rifaximin. Mini Rev. Med. Chem. 16, 179–185 (2015).

    Article  PubMed  CAS  Google Scholar 

  99. Maccaferri, S. et al. Rifaximin modulates the colonic microbiota of patients with Crohn's disease: an in vitro approach using a continuous culture colonic model system. J. Antimicrob. Chemother. 65, 2556–2565 (2010).

    Article  CAS  PubMed  Google Scholar 

  100. Weber, D. et al. Rifaximin preserves intestinal microbiota balance in patients undergoing allogeneic stem cell transplantation. Bone Marrow Transplant. 51, 1087–1092 (2016). This retrospective study describes the preserved diversity and better allo-HSCT outcomes with rifaximin as compared with a ciprofloxacin and metronidazole decontamination regimen.

    Article  CAS  PubMed  Google Scholar 

  101. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/study/NCT02641236 (2016).

  102. Kaysen, A. et al. Integrated meta-omic analyses of the gastrointestinal tract microbiome in patients undergoing allogeneic hematopoietic stem cell transplantation. Transl Res. 186, 79–94.e1 (2017).

    Article  PubMed  Google Scholar 

  103. Wen, L. et al. Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature 455, 1109–1113 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Mazmanian, S. K., Round, J. L. & Kasper, D. L. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453, 620–625 (2008).

    Article  CAS  PubMed  Google Scholar 

  105. Rooks, M. G. & Garrett, W. S. Gut microbiota, metabolites and host immunity. Nat. Rev. Immunol. 16, 341–352 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Smith, P. M. et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341, 569–573 (2013).

    Article  CAS  PubMed  Google Scholar 

  107. Maslowski, K. M. et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461, 1282–1286 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Wong, J. M., de Souza, R., Kendall, C. W., Emam, A. & Jenkins, D. J. Colonic health: fermentation and short chain fatty acids. J. Clin. Gastroenterol. 40, 235–243 (2006).

    Article  CAS  PubMed  Google Scholar 

  109. Iida, N. et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science 342, 967–970 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Paulos, C. M. et al. Microbial translocation augments the function of adoptively transferred self/tumor-specific CD8+ T cells via TLR4 signaling. J. Clin. Invest. 117, 2197–2204 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Peuker, K. et al. Epithelial calcineurin controls microbiota-dependent intestinal tumor development. Nat. Med. 22, 506–515 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Sivan, A. et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 350, 1084–1089 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Vetizou, M. et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350, 1079–1084 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Viaud, S. et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science 342, 971–976 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Zitvogel, L., Ayyoub, M., Routy, B. & Kroemer, G. Microbiome and anticancer immunosurveillance. Cell 165, 276–287 (2016).

    Article  CAS  PubMed  Google Scholar 

  116. Zitvogel, L., Daillere, R., Roberti, M. P., Routy, B. & Kroemer, G. Anticancer effects of the microbiome and its products. Nat. Rev. Microbiol. 15, 465–478 (2017).

    Article  CAS  PubMed  Google Scholar 

  117. Blazar, B. R., Murphy, W. J. & Abedi, M. Advances in graft-versus-host disease biology and therapy. Nat. Rev. Immunol. 12, 443–458 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Rajilic-Stojanovic, M. & de Vos, W. M. The first 1000 cultured species of the human gastrointestinal microbiota. FEMS Microbiol. Rev. 38, 996–1047 (2014).

    Article  CAS  PubMed  Google Scholar 

  119. Kanauchi, O. et al. Eubacterium limosum ameliorates experimental colitis and metabolite of microbe attenuates colonic inflammatory action with increase of mucosal integrity. World J. Gastroenterol. 12, 1071–1077 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  120. Peled, J. U., Jenq, R. R., Holler, E. & van den Brink, M. R. Role of gut flora after bone marrow transplantation. Nat. Microbiol. 1, 16036 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. de Gunzburg, J. et al. Targeted adsorption of molecules in the colon with the novel adsorbent-based medicinal product, DAV132: A proof of concept study in healthy subjects. J. Clin. Pharmacol. 55, 10–16 (2015).

    Article  CAS  PubMed  Google Scholar 

  122. Kaleko, M. et al. Development of SYN-004, an oral beta-lactamase treatment to protect the gut microbiome from antibiotic-mediated damage and prevent Clostridium difficile infection. Anaerobe 41, 58–67 (2016).

    Article  CAS  PubMed  Google Scholar 

  123. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/study/NCT02805075 (2016).

  124. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/study/NCT02763033(2016).

  125. Venkataraman, A. et al. Variable responses of human microbiomes to dietary supplementation with resistant starch. Microbiome 4, 33 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Kakihana, K. et al. Fecal microbiota transplantation for patients with steroid-resistant acute graft-versus-host disease of the gut. Blood 128, 2083–2088 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Spindelboeck, W. et al. Repeated fecal microbiota transplantations attenuate diarrhea and lead to sustained changes in the fecal microbiota in acute, refractory gastrointestinal graft-versus-host-disease. Haematologica 102, e210–e213 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  128. Youngster, I. et al. Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection. JAMA 312, 1772–1778 (2014).

    Article  CAS  PubMed  Google Scholar 

  129. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/study/NCT02733744 (2017).

  130. Song, S. J. et al. Cohabiting family members share microbiota with one another and with their dogs. eLife 2, e00458 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  131. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02218151 (2016).

  132. Gerbitz, A. et al. Probiotic effects on experimental graft-versus-host disease: let them eat yogurt. Blood 103, 4365–4367 (2004).

    Article  CAS  PubMed  Google Scholar 

  133. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/study/NCT02144701 (2017).

  134. Mehta, A., Rangarajan, S. & Borate, U. A cautionary tale for probiotic use in hematopoietic SCT patients-Lactobacillus acidophilus sepsis in a patient with mantle cell lymphoma undergoing hematopoietic SCT. Bone Marrow Transplant. 48, 461–462 (2013).

    Article  CAS  PubMed  Google Scholar 

  135. Fukuda, S. et al. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature 469, 543–547 (2011).

    Article  CAS  PubMed  Google Scholar 

  136. Bouazzaoui, A. et al. Reduction of aGVHD using chicken antibodies directed against intestinal pathogens in a murine model. Blood 129, 1052–1055 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Ott, S. J. et al. Efficacy of sterile fecal filtrate transfer for treating patients with Clostridium difficile infection. Gastroenterology 152, 799–811 (2017).

    Article  PubMed  Google Scholar 

  138. Weber, D. et al. Low urinary indoxyl sulfate levels early after transplantation reflect a disrupted microbiome and are associated with poor outcome. Blood 126, 1723–1728 (2015).

    Article  CAS  PubMed  Google Scholar 

  139. Lamas, B. et al. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. Nature Med. 22, 598–605 (2016).

    Article  CAS  PubMed  Google Scholar 

  140. Rayes, A. et al. A genetic modifier of the gut microbiome influences the risk of graft-versus-host disease and bacteremia after hematopoietic stem cell transplantation. Biol. Blood Marrow Transplant. 22, 418–422 (2016).

    Article  PubMed  Google Scholar 

  141. Rausch, P. et al. Colonic mucosa-associated microbiota is influenced by an interaction of Crohn disease and FUT2 (Secretor) genotype. Proc. Natl Acad. Sci. USA 108, 19030–19035 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Rouquier, S. et al. Molecular cloning of a human genomic region containing the H blood group alpha(1,2)fucosyltransferase gene and two H locus-related DNA restriction fragments. Isolation of a candidate for the human Secretor blood group locus. J. Biol. Chem. 270, 4632–4639 (1995).

    Article  CAS  PubMed  Google Scholar 

  143. Wacklin, P. et al. Secretor genotype (FUT2 gene) is strongly associated with the composition of Bifidobacteria in the human intestine. PLoS ONE 6, e20113 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Gupta, V. K., Paul, S. & Dutta, C. Geography, ethnicity or subsistence-specific variations in human microbiome composition and diversity. Front. Microbiol. 8, 1162 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  145. Yatsunenko, T. et al. Human gut microbiome viewed across age and geography. Nature 486, 222–227 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Kline, K. A., Falker, S., Dahlberg, S., Normark, S. & Henriques-Normark, B. Bacterial adhesins in host-microbe interactions. Cell Host Microbe 5, 580–592 (2009).

    Article  CAS  PubMed  Google Scholar 

  147. Khosravi, A. et al. Gut microbiota promote hematopoiesis to control bacterial infection. Cell Host Microbe 15, 374–381 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Fiedler, K., Kokai, E., Bresch, S. & Brunner, C. MyD88 is involved in myeloid as well as lymphoid hematopoiesis independent of the presence of a pathogen. Am. J. Blood Res. 3, 124–140 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  149. Yanez, A., Goodridge, H. S., Gozalbo, D. & Gil, M. L. TLRs control hematopoiesis during infection. Eur. J. Immunol. 43, 2526–2533 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Iwamura, C., Bouladoux, N., Belkaid, Y., Sher, A. & Jankovic, D. Sensing of the microbiota by NOD1 in mesenchymal stromal cells regulates murine hematopoiesis. Blood 129, 171–176 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Josefsdottir, K. S., Baldridge, M. T., Kadmon, C. S. & King, K. Y. Antibiotics impair murine hematopoiesis by depleting the intestinal microbiota. Blood 129, 729–739 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Beura, L. K. et al. Normalizing the environment recapitulates adult human immune traits in laboratory mice. Nature 532, 512–516 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Reese, T. A. et al. Sequential infection with common pathogens promotes human-like immune gene expression and altered vaccine response. Cell Host Microbe 19, 713–719 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Schulte, C., Reinhardt, W., Beelen, D., Mann, K. & Schaefer, U. Low T3-syndrome and nutritional status as prognostic factors in patients undergoing bone marrow transplantation. Bone Marrow Transplant. 22, 1171–1178 (1998).

    Article  CAS  PubMed  Google Scholar 

  155. Ursell, L. K., Metcalf, J. L., Parfrey, L. W. & Knight, R. Defining the human microbiome. Nutr. Rev. 70 (Suppl. 1), S38–44 (2012).

    Article  PubMed  Google Scholar 

  156. Cotillard, A. et al. Dietary intervention impact on gut microbial gene richness. Nature 500, 585–588 (2013).

    Article  CAS  PubMed  Google Scholar 

  157. Baumgartner, A. et al. Revisiting nutritional support for allogeneic hematologic stem cell transplantation — a systematic review. Bone Marrow Transplant. 52, 506–513 (2017).

    Article  CAS  PubMed  Google Scholar 

  158. van der Meij, B. S. et al. Nutritional support in patients with GVHD of the digestive tract: state of the art. Bone Marrow Transplant. 48, 474–482 (2013).

    Article  CAS  PubMed  Google Scholar 

  159. Martin-Salces, M., de Paz, R., Canales, M. A., Mesejo, A. & Hernandez-Navarro, F. Nutritional recommendations in hematopoietic stem cell transplantation. Nutrition 24, 769–775 (2008).

    Article  CAS  PubMed  Google Scholar 

  160. Rzepecki, P., Barzal, J. & Oborska, S. Blood and marrow transplantation and nutritional support. Supportive Care Cancer 18 (Suppl. 2), S57–S65 (2010).

    Article  Google Scholar 

  161. Flowers, M. E. et al. Long-Term Follow-Up After Hematopoietic Stem Cell Transplant. General Guidelines for Referring Physicians (Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance, Seattle, 2008).

    Google Scholar 

  162. van der Meij, B. S., Wierdsma, N. J., Janssen, J. J., Deutz, N. E. & Visser, O. J. If the gut works, use it! But does the gut work in gastrointestinal GvHD? Bone Marrow Transplant. 52, 466–469 (2017).

    Article  CAS  PubMed  Google Scholar 

  163. Murray, S. M. & Pindoria, S. Nutrition support for bone marrow transplant patients. Cochrane Database Syst. Rev. 1, CD002920 (2009).

    Google Scholar 

  164. Seguy, D. et al. Enteral feeding and early outcomes of patients undergoing allogeneic stem cell transplantation following myeloablative conditioning. Transplantation 82, 835–839 (2006).

    Article  PubMed  Google Scholar 

  165. Svahn, B. M. et al. Case-control comparison of at-home and hospital care for allogeneic hematopoietic stem-cell transplantation: the role of oral nutrition. Transplantation 85, 1000–1007 (2008).

    Article  PubMed  Google Scholar 

  166. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/study/NCT01955772 (2016).

  167. Taur, Y. Intestinal microbiome changes and stem cell transplantation: lessons learned. Virulence 7, 930–938 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/study/NCT03102060 (2017).

  169. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/study/NCT02461199 (2015).

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Acknowledgements

The authors thank O.M. Smith for editing the manuscript and E. Velardi, J. U. Peled and C. Stein-Thoeringer for their scientific input and editing of the manuscript. This research was supported by US National Institutes of Health award numbers R01-HL069929 (M.R.M.v.d.B.), R01-AI101406 (M.R.M.v.d.B.), P01-CA023766 (R. J. O'Reilly), Project 4 of P01-CA023766 (M.R.M.v.d.B.), 1R01HL123340-01A1 (K. Cadwell) and R01–AI100288 (M.R.M.v.d.B.). Support was also received from The American Society for Blood and Marrow Transplantation (Y.S.), The Lymphoma Foundation, The Susan and Peter Solomon Divisional Genomics Program, Cycle for Survival and P30 CA008748 Memorial Sloan Kettering Cancer Center Support Grant/Core Grant. This research was also supported by the Parker Institute for Cancer Immunotherapy at Memorial Sloan Kettering Cancer Center.

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Authors and Affiliations

  1. Department of Immunology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York, USA

    Yusuke Shono & Marcel R. M. van den Brink

  2. Department of Medicine, State University of New York Downstate Medical Center, Brooklyn, New York, USA

    Yusuke Shono

  3. Weill Medical College of Cornell University, New York, New York, USA

    Marcel R. M. van den Brink

  4. Department of Medicine, Adult BMT Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA

    Marcel R. M. van den Brink

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Contributions

Y.S. researched data for the article. M.R.M.v.d.B. and Y.S. made substantial contributions to discussion of content and wrote, reviewed and edited the manuscript.

Corresponding author

Correspondence to Marcel R. M. van den Brink.

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Competing interests

Memorial Sloan Kettering Cancer Center has filed patent applications related to this work (PCT/US2015/062734 entitled INTESTINAL MICROBIOTA AND GVHD; inventors include M.R.M.v.d.B. and Y.S.). M.R.M.v.d.B. received research funding from Seres Therapeutics, and M.R.M.v.d.B. and Y.S. received licensing fees from Seres.

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Glossary

Alloreactive donor T cells

T cells that have been activated after encountering antigens within the context of major histocompatibility complex (MHC) molecules other than those present during thymic selection. After allogeneic haematopoietic stem cell transplantation, T cells can be allogeneically activated by encounter with an unknown (foreign) MHC molecule (major histocompatibility mismatch) or with a known (matched) MHC molecule presenting a foreign antigen (minor histocompatibility mismatch).

Neutropenia

A condition of abnormally low numbers of neutrophils within the blood. This is an immune system condition that may lead to infections.

Febrile neutropenia

(FN). The development of fever, often with other signs of infections, occurring during the period of low neutrophil counts (neutropenia) after allogeneic haematopoietic stem cell transplantation or chemotherapy for cancer. Neutropenia typically occurs 8–12 days after chemotherapy and typically lasts for 10–25 days.

Bacteraemia

The presence of bacteria in the blood (usually resulting from impaired gut barrier function owing to a conditioning regimen and/or graft-versus- host disease in allogeneic haematopoietic stem cell transplantation) that leads to sepsis.

Facultative bacteria

A category of bacteria that can thrive under aerobic or anaerobic conditions.

Gut consortium

A group of microbiota species or strains. Interactions among the members of a consortium may form an ecological community in which members compete with one another or in which products of one member are utilized by or are toxic to another member.

Sepsis

The immune reaction of the host to bacteria.

Bacterial ligands

Components of the bacterial cell surface that interact with the host cell receptor. They interact with phagocytes and stimulate subsequent evasion of innate immune responses.

Innate lymphoid cells

(ILCs). A population of immune lymphoid cells that are morphologically similar to B cells and T cells but lack pattern-recognition receptors and rearranged antigen receptors (and thus are unable to directly mediate antigen-specific responses). They secrete a high concentration of cytokines and play key roles in effector and regulatory functions in innate immunity, metabolic homeostasis and tissue remodelling.

Germ-free mice

Also known as gnotobiotic mice, these mice are maintained under strictly sterile conditions in which absolutely no bacteria are present in or on the animals. Individual bacterial strains or groups of strains (consortia) can be introduced in a controlled fashion (axenic conditions).

Aplastic anaemia

A form of bone marrow failure in which the bone marrow cannot make enough new blood cells. It is characterized by peripheral pancytopenia (decrease of red blood cells, white blood cells and platelets) and bone marrow hypoplasia.

Laminar-airflow isolation

A method that provides a low-pathogen environment and prevents exogenous infection during hospitalization of patients with neutropenia and other immunodeficient diseases. It involves filtered air moving along separate parallel flow planes to patient rooms with no or minimal crossover of air streams (or lamina).

Specific pathogen-free (SPF) mice

Mice housed under standard laboratory conditions. These mice are free of specific pathogens but otherwise have a normal microbiota. The lists of specific pathogens tested vary by supplier and institution and typically include opportunistic organisms that do not cause illness in immunocompetent hosts but can be harmful to immunocompromised mice, for example, after allogeneic haematopoietic stem cell transplantation.

Oral nutrition

The intake of food through the mouth and oesophagus to provide nutrients for health.

Total parenteral nutrition

A method to feed a person intravenously, completely bypassing the usual process of eating and digestion. The nutritional formulae typically include glucose, amino acids, lipids and salts, with the supplementation of vitamins and minerals as needed.

16S ribosomal RNA sequence

A method used for identification, classification and quantification of microorganisms (the 16S ribosomal RNA subunit is an essential, highly conserved component in the 30S ribosomal complex in prokaryotes).

Enteral nutrition

A method of delivering a person's calorific nutritional requirements by use of a tube (tube feeding) into the stomach, achieved by syringe, gravity or pump.

Pathobiont

A potentially harmful (disease-causing or pathological) organism that under normal conditions lives as a component of a healthy microbiota population (symbiont).

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Shono, Y., van den Brink, M. Gut microbiota injury in allogeneic haematopoietic stem cell transplantation. Nat Rev Cancer 18, 283–295 (2018). https://doi.org/10.1038/nrc.2018.10

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