open access

Vol 53, No 6 (2022)
Review article
Submitted: 2022-07-27
Accepted: 2022-10-02
Published online: 2022-11-22
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Influence of gut microbiota on efficacy and adverse effects of treatment of lymphoproliferative disorders

Klaudia Zielonka1, Marcin Jasiński12, Krzysztof Jamroziak1
DOI: 10.5603/AHP.a2022.0053
·
Acta Haematol Pol 2022;53(6):363-375.
Affiliations
  1. Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, Warszawa, Poland
  2. Doctoral School, Medical University of Warsaw, Warszawa, Poland

open access

Vol 53, No 6 (2022)
REVIEW ARTICLE
Submitted: 2022-07-27
Accepted: 2022-10-02
Published online: 2022-11-22

Abstract

Gut microbiota has aroused great interest because of its influence on the human body's homeostasis. In addition, multiple reports have indicated its role in the pathogenesis of various diseases. Interestingly, gut microbiota can affect hematological disorders by participating in lymphomagenesis. Patients with lymphoproliferative disorders undergo many procedures that alter their unique microbiota composition and lead to dysbiosis. However, this can have a biased effect as many studies have highlighted gut microbiota’s activity in chemotherapy efficacy, for instance by either enhancing the anti-malignant effects of cyclophosphamide or by diminishing the activity of doxorubicin or cladribine. This review aimed to summarize gut microbiota’s influence on chemotherapy’s outcomes on treatment-related side effects in lymphoproliferative disorders, antimicrobial regimens, and possible gut microbiota modifications to enhance treatment outcomes.

Abstract

Gut microbiota has aroused great interest because of its influence on the human body's homeostasis. In addition, multiple reports have indicated its role in the pathogenesis of various diseases. Interestingly, gut microbiota can affect hematological disorders by participating in lymphomagenesis. Patients with lymphoproliferative disorders undergo many procedures that alter their unique microbiota composition and lead to dysbiosis. However, this can have a biased effect as many studies have highlighted gut microbiota’s activity in chemotherapy efficacy, for instance by either enhancing the anti-malignant effects of cyclophosphamide or by diminishing the activity of doxorubicin or cladribine. This review aimed to summarize gut microbiota’s influence on chemotherapy’s outcomes on treatment-related side effects in lymphoproliferative disorders, antimicrobial regimens, and possible gut microbiota modifications to enhance treatment outcomes.

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Keywords

microbiota, chemotherapy, lymphoproliferative disorders

About this article
Title

Influence of gut microbiota on efficacy and adverse effects of treatment of lymphoproliferative disorders

Journal

Acta Haematologica Polonica

Issue

Vol 53, No 6 (2022)

Article type

Review article

Pages

363-375

Published online

2022-11-22

Page views

573

Article views/downloads

63

DOI

10.5603/AHP.a2022.0053

Bibliographic record

Acta Haematol Pol 2022;53(6):363-375.

Keywords

microbiota
chemotherapy
lymphoproliferative disorders

Authors

Klaudia Zielonka
Marcin Jasiński
Krzysztof Jamroziak

References (97)
  1. Lee KA, Luong MK, Shaw H, et al. The gut microbiome: what the oncologist ought to know. Br J Cancer. 2021; 125(9): 1197–1209.
  2. Peaudecerf L, Rocha B. Role of the gut as a primary lymphoid organ. Immunol Lett. 2011; 140(1-2): 1–6.
  3. Adak A, Khan MR. An insight into gut microbiota and its functionalities. Cell Mol Life Sci. 2019; 76(3): 473–493.
  4. Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010; 464(7285): 59–65.
  5. Bäckhed F, Ley R, Sonnenburg J, et al. Host-bacterial mutualism in the human intestine. Science. 2005; 307(5717): 1915–1920.
  6. Levy M, Kolodziejczyk A, Thaiss C, et al. Dysbiosis and the immune system. Nat Rev Immunol. 2017; 17(4): 219–232.
  7. Xu JYi, Liu MM, Tao TT, et al. The role of gut microbiota in tumorigenesis and treatment. Biomed Pharmacother. 2021; 138: 111444.
  8. Rinninella E, Raoul P, Cintoni M, et al. What is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseases. Microorganisms. 2019; 7(1).
  9. Lozupone CA, Stombaugh JI, Gordon JI, et al. Diversity, stability and resilience of the human gut microbiota. Nature. 2012; 489(7415): 220–230.
  10. Eckburg PB, Bik EM, Bernstein CN, et al. Diversity of the human intestinal microbial flora. Science. 2005; 308(5728): 1635–1638.
  11. Hallek M, Cheson BD, Catovsky D, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018; 131(25): 2745–2760.
  12. Bass KK, Mastrangelo MJ. Immunopotentiation with low-dose cyclophosphamide in the active specific immunotherapy of cancer. Cancer Immunol Immunother. 1998; 47(1): 1–12.
  13. Viaud S, Saccheri F, Mignot G, et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science. 2013; 342(6161): 971–976.
  14. Daillère R, Vétizou M, Waldschmitt N, et al. Enterococcus hirae and Barnesiella intestinihominis facilitate cyclophosphamide-induced therapeutic immunomodulatory effects. Immunity. 2016; 45(4): 931–943.
  15. Pflug N, Kluth S, Vehreschild JJ, et al. Efficacy of antineoplastic treatment is associated with the use of antibiotics that modulate intestinal microbiota. Oncoimmunology. 2016; 5(6): e1150399.
  16. Lehouritis P, Cummins J, Stanton M, et al. Local bacteria affect the efficacy of chemotherapeutic drugs. Sci Rep. 2015; 5: 14554.
  17. Hoogeboom R, van Kessel KPM, Hochstenbach F, et al. A mutated B cell chronic lymphocytic leukemia subset that recognizes and responds to fungi. J Exp Med. 2013; 210(1): 59–70.
  18. Hooi JKY, Lai WY, Ng WK, et al. Global prevalence of Helicobacter pylori infection: systematic review and meta-analysis. Gastroenterology. 2017; 153(2): 420–429.
  19. Jasiński M, Biliński J, Basak GW. The role of the crosstalk between gut microbiota and immune cells in the pathogenesis and treatment of multiple myeloma. Front Immunol. 2022; 13: 853540.
  20. Jian X, Zhu Y, Ouyang J, et al. Alterations of gut microbiome accelerate multiple myeloma progression by increasing the relative abundances of nitrogen-recycling bacteria. Microbiome. 2020; 8(1): 74.
  21. Bolzoni M, Chiu M, Accardi F, et al. Dependence on glutamine uptake and glutamine addiction characterize myeloma cells: a new attractive target. Blood. 2016; 128(5): 667–679.
  22. Nucci M, Anaissie E. Infections in patients with multiple myeloma. Semin Hematol. 2009; 46(3): 277–288.
  23. Calcinotto A, Brevi A, Chesi M, et al. Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression. Nat Commun. 2018; 9(1): 4832.
  24. Alkharabsheh O, Sidiqi MH, Aljama MA, et al. The human microbiota in multiple myeloma and proteasome inhibitors. Acta Haematol. 2020; 143(2): 118–123.
  25. Stansborough RL, Gibson RJ. Proteasome inhibitor-induced gastrointestinal toxicity. Curr Opin Support Palliat Care. 2017; 11(2): 133–137.
  26. Yamamoto S, Egashira N. Pathological mechanisms of bortezomib-induced peripheral neuropathy. Int J Mol Sci. 2021; 22(2).
  27. Zhong S, Zhou Z, Liang Y, et al. Targeting strategies for chemotherapy-induced peripheral neuropathy: does gut microbiota play a role? Crit Rev Microbiol. 2019; 45(4): 369–393.
  28. Pianko MJ, Devlin SM, Littmann ER, et al. Minimal residual disease negativity in multiple myeloma is associated with intestinal microbiota composition. Blood Adv. 2019; 3(13): 2040–2044.
  29. Asao K, Hashida N, Ando S, et al. Conjunctival dysbiosis in mucosa-associated lymphoid tissue lymphoma. Sci Rep. 2019; 9(1): 8424.
  30. Travaglino A, Pace M, Varricchio S, et al. Prevalence of Chlamydia psittaci, Chlamydia pneumoniae, and Chlamydia trachomatis Determined by Molecular Testing in Ocular Adnexa Lymphoma Specimens. Am J Clin Pathol. 2020; 153(4): 427–434.
  31. Schmelz R, Miehlke S, Thiede C, et al. Sequential H. pylori eradication and radiation therapy with reduced dose compared to standard dose for gastric MALT lymphoma stages IE & II1E: a prospective randomized trial. J Gastroenterol. 2019; 54(5): 388–395.
  32. Ferreri AJM, Ponzoni M, Guidoboni M, et al. Bacteria-eradicating therapy with doxycycline in ocular adnexal MALT lymphoma: a multicenter prospective trial. J Natl Cancer Inst. 2006; 98(19): 1375–1382.
  33. O'Rourke JL, Dixon MF, Jack A, et al. Gastric B-cell mucosa-associated lymphoid tissue (MALT) lymphoma in an animal model of 'Helicobacter heilmannii' infection. J Pathol. 2004; 203(4): 896–903.
  34. Chang CM, Landgren O, Koshiol J, et al. Borrelia and subsequent risk of solid tumors and hematologic malignancies in Sweden. Int J Cancer. 2012; 131(9): 2208–2209.
  35. Schöllkopf C, Melbye M, Munksgaard L, et al. Borrelia infection and risk of non-Hodgkin lymphoma. Blood. 2008; 111(12): 5524–5529.
  36. Yamamoto ML, Maier I, Dang AT, et al. Intestinal bacteria modify lymphoma incidence and latency by affecting systemic inflammatory state, oxidative stress, and leukocyte genotoxicity. Cancer Res. 2013; 73(14): 4222–4232.
  37. He MY, Kridel R. Treatment resistance in diffuse large B-cell lymphoma. Leukemia. 2021; 35(8): 2151–2165.
  38. Yuan Li, Wang W, Zhang W, et al. Gut microbiota in untreated diffuse large B cell lymphoma patients. Front Microbiol. 2021; 12: 646361.
  39. Diefenbach CS, Peters BA, Li H, et al. Microbial dysbiosis is associated with aggressive histology and adverse clinical outcome in B-cell non-Hodgkin lymphoma. Blood Adv. 2021; 5(5): 1194–1198.
  40. Sivan A, Corrales L, Hubert N, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015; 350(6264): 1084–1089.
  41. Routy B, Chatelier ELe, Derosa L, et al. Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors. Science. 2018; 359(6371): 91–97.
  42. Iida N, Dzutsev A, Stewart CA, et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science. 2013; 342(6161): 967–970.
  43. Vande Voorde J, Sabuncuoğlu S, Noppen S, et al. Nucleoside-catabolizing enzymes in mycoplasma-infected tumor cell cultures compromise the cytostatic activity of the anticancer drug gemcitabine. J Biol Chem. 2014; 289(19): 13054–13065.
  44. Geller LT, Barzily-Rokni M, Danino T, et al. Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. Science. 2017; 357(6356): 1156–1160.
  45. Rigby RJ, Carr J, Orgel K, et al. Intestinal bacteria are necessary for doxorubicin-induced intestinal damage but not for doxorubicin-induced apoptosis. Gut Microbes. 2016; 7(5): 414–423.
  46. Nigro G, Rossi R, Commere PH, et al. The cytosolic bacterial peptidoglycan sensor Nod2 affords stem cell protection and links microbes to gut epithelial regeneration. Cell Host Microbe. 2014; 15(6): 792–798.
  47. Gopal KV, Wu C, Shrestha B, et al. d-Methionine protects against cisplatin-induced neurotoxicity in cortical networks. Neurotoxicol Teratol. 2012; 34(5): 495–504.
  48. Wu CH, Ko JL, Liao JM, et al. D-methionine alleviates cisplatin-induced mucositis by restoring the gut microbiota structure and improving intestinal inflammation. Ther Adv Med Oncol. 2019; 11: 1758835918821021.
  49. Zhao L, Xing C, Sun W, et al. Lactobacillus supplementation prevents cisplatin-induced cardiotoxicity possibly by inflammation inhibition. Cancer Chemother Pharmacol. 2018; 82(6): 999–1008.
  50. Yamamoto ML, Schiestl RH. Intestinal microbiome and lymphoma development. Cancer J. 2014; 20(3): 190–194.
  51. Wei W, Sun W, Yu S, et al. Butyrate production from high-fiber diet protects against lymphoma tumor. Leuk Lymphoma. 2016; 57(10): 2401–2408.
  52. Pryde SE, Duncan S, Hold G, et al. The microbiology of butyrate formation in the human colon. FEMS Microbiology Letters. 2002; 217(2): 133–139.
  53. Zhao B, Zhou B, Dong C, et al. Alleviates gastrointestinal toxicity of rituximab by regulating the proinflammatory T cells . Front Microbiol. 2021; 12: 645500.
  54. Cozen W, Yu G, Gail MH, et al. Fecal microbiota diversity in survivors of adolescent/young adult Hodgkin lymphoma: a study of twins. Br J Cancer. 2013; 108(5): 1163–1167.
  55. Huang J, Wei S, Jiang C, et al. Involvement of abnormal gut microbiota composition and function in doxorubicin-induced cardiotoxicity. Front Cell Infect Microbiol, 2022; 12.
  56. Zhu H. Doxorubicin-induced cardiotoxicity. Cardiotoxicity. 2018.
  57. Xu-Monette ZY, Zhou J, Young KH. PD-1 expression and clinical PD-1 blockade in B-cell lymphomas. Blood. 2018; 131(1): 68–83.
  58. Dzutsev A, Goldszmid RS, Viaud S, et al. The role of the microbiota in inflammation, carcinogenesis, and cancer therapy. Eur J Immunol. 2015; 45(1): 17–31.
  59. Davar D, Dzutsev AK, McCulloch JA, et al. Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients. Science. 2021; 371(6529): 595–602.
  60. Elkrief A, Derosa L, Kroemer G, et al. The negative impact of antibiotics on outcomes in cancer patients treated with immunotherapy: a new independent prognostic factor? Ann Oncol. 2019; 30(10): 1572–1579.
  61. Derosa L, Hellmann MD, Spaziano M, et al. Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer. Ann Oncol. 2018; 29(6): 1437–1444.
  62. Pallister T, Jackson MA, Martin TC, et al. Hippurate as a metabolomic marker of gut microbiome diversity: modulation by diet and relationship to metabolic syndrome. Sci Rep. 2017; 7(1): 13670.
  63. Spencer CN, Gopalakrishnan V, McQuade J. Abstract 2838: The gut microbiome (GM) and immunotherapy response are influenced by host lifestyle factors Atlanta, GA, Conference: Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019.
  64. Duarte RF, Labopin M, Bader P, et al. European Society for Blood and Marrow Transplantation (EBMT). Indications for haematopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2019. Bone Marrow Transplant. 2019; 54(10): 1525–1552.
  65. Kusakabe S, Fukushima K, Maeda T, et al. Pre- and post-serial metagenomic analysis of gut microbiota as a prognostic factor in patients undergoing haematopoietic stem cell transplantation. Br J Haematol. 2020; 188(3): 438–449.
  66. Weber D, Oefner PJ, Dettmer K, et al. Rifaximin preserves intestinal microbiota balance in patients undergoing allogeneic stem cell transplantation. Bone Marrow Transplantation. 2016; 51(8): 1087–1092.
  67. Montassier E, Gastinne T, Vangay P, et al. Chemotherapy-driven dysbiosis in the intestinal microbiome. Aliment Pharmacol Ther. 2015; 42(5): 515–528.
  68. Sahin U, Kocak Toprak S, Ataca Atilla P, et al. An overview of infectious complications after allogeneic hematopoietic stem cell transplantation. J Infect Chemother. 2016; 22(8): 505–514.
  69. El Jurdi N, Filali-Mouhim A, Salem I, et al. Gastrointestinal microbiome and mycobiome changes during autologous transplantation for multiple myeloma: results of a prospective pilot study. Biol Blood Marrow Transplant. 2019; 25(8): 1511–1519.
  70. Doki N, Suyama M, Sasajima S, et al. Clinical impact of pre-transplant gut microbial diversity on outcomes of allogeneic hematopoietic stem cell transplantation. Ann Hematol. 2017; 96(9): 1517–1523.
  71. Peled JU, Devlin SM, Staffas A, et al. Intestinal microbiota and relapse after hematopoietic-cell transplantation. J Clin Oncol. 2017; 35(15): 1650–1659.
  72. Malard F, Lavelle A, Battipaglia G, et al. Impact of gut fungal and bacterial communities on the outcome of allogeneic hematopoietic cell transplantation. Mucosal Immunol. 2021; 14(5): 1127–1132.
  73. Taur Y, Jenq RR, Perales MA, et al. The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation. Blood. 2014; 124(7): 1174–1182.
  74. Schluter J, Peled JU, Taylor BP, et al. The gut microbiota is associated with immune cell dynamics in humans. Nature. 2020; 588(7837): 303–307.
  75. Weber D, Oefner PJ, Hiergeist A, et al. Low urinary indoxyl sulfate levels early after transplantation reflect a disrupted microbiome and are associated with poor outcome. Blood. 2015; 126(14): 1723–1728.
  76. Mathewson ND, Jenq R, Mathew A, et al. Gut microbiome–derived metabolites modulate intestinal epithelial cell damage and mitigate graft-versus-host disease. Nat Immunol. 2016; 17(5): 505–513.
  77. Simms-Waldrip TR, Sunkersett G, Coughlin LA, 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(5): 820–829.
  78. Andermann TM, Fouladi F, Tamburini FB, et al. A fructo-oligosaccharide prebiotic is well tolerated in adults undergoing allogeneic hematopoietic stem cell transplantation: a phase I dose-escalation trial. Transplant Cell Ther. 2021; 27(11): 932.e1–932.e11.
  79. Golob JL, Pergam SA, Srinivasan S, et al. Stool microbiota at neutrophil recovery is predictive for severe acute graft vs host disease After Hematopoietic Cell Transplantation. Clin Infect Dis. 2017; 65(12): 1984–1991.
  80. Jenq RR, Ubeda C, Taur Y, et al. Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation. J Exp Med. 2012; 209(5): 903–911.
  81. Schubert ML, Rohrbach R, Schmitt M, et al. The potential role of the intestinal micromilieu and individual microbes in the immunobiology of chimeric antigen receptor T-cell therapy. Front Immunol. 2021; 12: 670286.
  82. Salerno F, Heeren JFv, Guislain A, et al. Costimulation through TLR2 drives polyfunctional CD8(+) T cell responses. J Immunol. 2019; 202(3): 714–723.
  83. Smith M, Dai A, Ghilardi G, et al. Gut microbiome correlates of response and toxicity following anti-CD19 CAR T cell therapy. Nat Med. 2022; 28(4): 713–723.
  84. Fanning SR, Rybicki L, Kalaycio M, et al. Severe mucositis is associated with reduced survival after autologous stem cell transplantation for lymphoid malignancies. Br J Haematol. 2006; 135(3): 374–381.
  85. Wang C, Li Q, Ren J. Microbiota-immune interaction in the pathogenesis of gut-derived infection. Front Immunol. 2019; 10: 1873.
  86. van Vliet MJ, Harmsen HJM, de Bont ES, et al. The role of intestinal microbiota in the development and severity of chemotherapy-induced mucositis. PLoS Pathog. 2010; 6(5): e1000879.
  87. Lakhdari O, Tap J, Béguet-Crespel, F, et al. Identification of NF-κB modulation capabilities within human intestinal commensal bacteria. J Biomed Biotechnol. 2011; 2011: 282356.
  88. Segain JP, Raingeard de la Blétière D, Bourreille A, et al. Butyrate inhibits inflammatory responses through NFkappaB inhibition: implications for Crohn's disease. Gut. 2000; 47(3): 397–403.
  89. Ferreira TM, Leonel AJ, Melo MA, et al. Oral supplementation of butyrate reduces mucositis and intestinal permeability associated with 5-fluorouracil administration. Lipids. 2012; 47(7): 669–678.
  90. Shin NR, Whon TW, Bae JW. Proteobacteria: microbial signature of dysbiosis in gut microbiota. Trends Biotechnol. 2015; 33(9): 496–503.
  91. Martin PJ, Schoch G, Fisher L, et al. A retrospective analysis of therapy for acute graft-versus-host disease: initial treatment. Blood. 1990; 76(8): 1464–1472.
  92. Giaccone L, Faraci DG, Butera S, et al. Biomarkers for acute and chronic graft versus host disease: state of the art. Expert Rev Hematol. 2021; 14(1): 79–96.
  93. Andersen S, Staudacher H, Weber N, et al. Pilot study investigating the effect of enteral and parenteral nutrition on the gastrointestinal microbiome post-allogeneic transplantation. Br J Haematol. 2020; 188(4): 570–581.
  94. Jenq RR, Taur Y, Devlin SM, et al. Intestinal blautia is associated with reduced death from graft-versus-host disease. Biol Blood Marrow Transplant. 2015; 21(8): 1373–1383.
  95. Kuczma MP, Ding ZC, Li T, et al. The impact of antibiotic usage on the efficacy of chemoimmunotherapy is contingent on the source of tumor-reactive T cells. Oncotarget. 2017; 8(67): 111931–111942.
  96. Biliński J, Jasiński M, Tomaszewska A, et al. Fecal microbiota transplantation with ruxolitinib as a treatment modality for steroid-refractory/dependent acute, gastrointestinal graft-versus-host disease: A case series. Am J Hematol. 2021; 96(12): E461–E463.
  97. Qi X, Li X, Zhao Ye, et al. Treating steroid refractory intestinal acute graft-vs-host disease with fecal microbiota transplantation: a pilot study. Front Immunol. 2018; 9: 2195.

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