The post-hematopoietic cell transplantation microbiome: relationships with transplant outcome and potential therapeutic targets

Yannouck F Van Lier, Marcel R M Van den Brink, Mette D Hazenberg, Kate A Markey, Yannouck F Van Lier, Marcel R M Van den Brink, Mette D Hazenberg, Kate A Markey

Abstract

Microbiota injury occurs in many patients undergoing allogeneic hematopoietic cell transplantation, likely as a consequence of conditioning regimens involving chemo- and radiotherapy, the widespread use of both prophylactic and therapeutic antibiotics, and profound dietary changes during the peri-transplant period. Peri-transplant dysbiosis is characterized by a decrease in bacterial diversity, loss of commensal bacteria and single-taxon domination (e.g., with Enterococcal strains). Clinically, deviation of the post-transplant microbiota from a normal, high-diversity, healthy state has been associated with increased risk of bacteremia, development of graft-versus-host disease and decreases in overall survival. A number of recent clinical trials have attempted to target the microbiota in allogeneic hematopoietic cell transplantation patients via dietary interventions, selection of therapeutic antibiotics, administration of pre- or pro-biotics, or by performing fecal microbiota transplantation. These strategies have yielded promising results but the mechanisms by which these interventions influence transplant-related complications remain largely unknown. In this review we summarize the current approaches to targeting the microbiota, discuss potential underlying mechanisms and highlight the key outstanding areas that require further investigation in order to advance microbiota- targeting therapies.

Figures

Figure 1.
Figure 1.
Timeline of potential microbiota perturbations after allogeneic hematopoietic cell transplantation. HCT: hematopoietic cell transplantation; TBI: total body irradiation. Created with BioRender.com
Figure 2.
Figure 2.
Interactions between the gut microbiota and mucosal immune system in steady state and peri-transplant environments. (A) Pre-transplant interaction between the intestinal tract, mucosal immune system and the microbiome. (B) Peri-transplant interaction between the inflamed intestinal tract, infiltrating donor populations, some of which alloreactive T cells that cause graft-versus-host disease, and the perturbed microbiome, often colonized with potential pathogens, such as Enterococcus faecalis/faecium. APC: antigen-presenting cell; DAMPS: damage-associated patterns; GvHD: graft-versus-host disease; LPS: lipopolysaccharides; PAMPS: pathogen-associated patterns. Created with BioRender.com

References

    1. Jagasia M, Arora M, Flowers ME, et al. . Risk factors for acute GVHD and survival after hematopoietic cell transplantation. Blood. 2012;119(1):296-307.
    1. D'Souza A, Fretham C, Lee SJ, et al. . Current use of and trends in hematopoietic cell transplantation in the United States. Biol Blood Marrow Transplant. 2020;26(8):e177-e182.
    1. Gooptu M, Koreth J. Translational and clinical advances in acute graft-versus-host disease. Haematologica. 2020;105(11):2550-2560.
    1. Sonis ST. The pathobiology of mucositis. Nat Rev Cancer. 2004;4(4):277-284.
    1. Bennett JE, Dolin R, Blaser MJ, Mandell GL, Douglas RG. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 2015. Eighth edition.
    1. Zeiser R, Blazar BR. Acute graft-versus-host disease - biologic process, prevention, and therapy. N Engl J Med. 2017;377(22):2167-2179.
    1. Antin JH, Ferrara JL. Cytokine dysregulation and acute graft-versus-host disease. Blood. 1992;80(12):2964-2968.
    1. MacMillan ML, Robin M, Harris AC, et al. . A refined risk score for acute graft-versus-host disease that predicts response to initial therapy, survival, and transplant-related mortality. Biol Blood Marrow Transplant. 2015;21(4):761-767.
    1. Jagasia M, Zeiser R, Arbushites M, Delaite P, Gadbaw B, Bubnoff NV. Ruxolitinib for the treatment of patients with steroid-refractory GVHD: an introduction to the REACH trials. Immunotherapy. 2018;10(5):391-402.
    1. 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):14.
    1. Amarasinghe SL, Su S, Dong X, Zappia L, Ritchie ME, Gouil Q. Opportunities and challenges in long-read sequencing data analysis. Genome Biol. 2020;21(1):30.
    1. Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI. The human microbiome project. Nature. 2007;449(7164):804-810.
    1. Falony G, Joossens M, Vieira-Silva S, et al. . Population-level analysis of gut microbiome variation. Science. 2016;352(6285):560-564.
    1. Zhernakova A, Kurilshikov A, Bonder MJ, et al. . Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity. Science. 2016;352 (6285):565-569.
    1. Jackson MA, Verdi S, Maxan ME, et al. . Gut microbiota associations with common diseases and prescription medications in a population- based cohort. Nat Commun. 2018;9(1):2655.
    1. Hooper LV, Macpherson AJ. Immune adaptations that maintain homeostasis with the intestinal microbiota. Nat Rev Immunol. 2010;10(3):159-169.
    1. Kamada N, Seo SU, Chen GY, Nunez G. Role of the gut microbiota in immunity and inflammatory disease. Nat Rev Immunol. 2013;13(5):321-335.
    1. Yatsunenko T, Rey FE, Manary MJ, et al. . Human gut microbiome viewed across age and geography. Nature. 2012;486(7402):222-227.
    1. Miller TL, Wolin MJ. Pathways of acetate, propionate, and butyrate formation by the human fecal microbial flora. Appl Environ Microbiol. 1996;62(5):1589-1592.
    1. Ridlon JM, Kang DJ, Hylemon PB. Bile salt biotransformations by human intestinal bacteria. J Lipid Res. 2006;47(2):241-259.
    1. Correa-Oliveira R, Fachi JL, Vieira A, Sato FT, Vinolo MA. Regulation of immune cell function by short-chain fatty acids. Clin Transl Immunology. 2016;5(4):e73.
    1. Tan J, McKenzie C, Potamitis M, Thorburn AN, Mackay CR, Macia L. The role of shortchain fatty acids in health and disease. Adv Immunol. 2014;121:91-119.
    1. Smith T. A modification of the method for determining the production of indol by bacteria. J Exp Med. 1897;2(5):543-547.
    1. Ridlon JM, Harris SC, Bhowmik S, Kang DJ, Hylemon PB. Consequences of bile salt biotransformations by intestinal bacteria. Gut Microbes. 2016;7(1):22-39.
    1. Sun M, Wu W, Chen L, et al. . Microbiotaderived short-chain fatty acids promote Th1 cell IL-10 production to maintain intestinal homeostasis. Nat Commun. 2018;9(1):3555.
    1. Dudakov JA, Hanash AM, van den Brink MR. Interleukin-22: immunobiology and pathology. Annu Rev Immunol. 2015;33: 747-785.
    1. Taur Y, Xavier JB, Lipuma L, et al. . Intestinal domination and the risk of bacteremia in patients undergoing allogeneic hematopoietic stem cell transplantation. Clin Infect Dis. 2012;55(7):905-914.
    1. Ubeda C, Taur Y, Jenq RR, 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. 2010;120(12):4332-4341.
    1. Taur Y, Coyte K, Schluter J, et al. . Reconstitution of the gut microbiota of antibiotic-treated patients by autologous fecal microbiota transplant. Sci Transl Med. 2018;10(460):eaa9489.
    1. Peled JU, Gomes ALC, Devlin SM, et al. . Microbiota as predictor of mortality in allogeneic hematopoietic-cell transplantation. N Engl J Med. 2020;382(9):822-834.
    1. Weber D, Jenq RR, Peled JU, 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. 2017;23(5):845-852.
    1. Shono Y, Docampo MD, Peled JU, 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(339):339ra371.
    1. 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.
    1. Lee SE, Lim JY, Ryu DB, et al. . Alteration of the intestinal microbiota by broad-spectrum antibiotic use correlates with the occurrence of intestinal graft-versus-host disease. Biol Blood Marrow Transplant. 2019;25(10): 1933-1943.
    1. van Vliet MJ, Tissing WJ, Dun CA, et al. . Chemotherapy treatment in pediatric patients with acute myeloid leukemia receiving antimicrobial prophylaxis leads to a relative increase of colonization with potentially pathogenic bacteria in the gut. Clin Infect Dis. 2009;49(2):262-270.
    1. Zwielehner J, Lassl C, Hippe B, et al. . Changes in human fecal microbiota due to chemotherapy analyzed by TaqMan-PCR, 454 sequencing and PCR-DGGE fingerprinting. PLoS One. 2011;6(12):e28654.
    1. Biagi E, Zama D, Nastasi C, et al. . Gut microbiota trajectory in pediatric patients undergoing hematopoietic SCT. Bone Marrow Transplant. 2015;50(7):992-998.
    1. Galloway-Pena JR, Shi Y, Peterson CB, et al. . Gut microbiome signatures are predictive of infectious risk following induction therapy for acute myeloid leukemia. Clin Infect Dis. 2020;71(1):63-71.
    1. Montassier E, Gastinne T, Vangay P, et al. . Chemotherapy-driven dysbiosis in the intestinal microbiome. Aliment Pharmacol Ther. 2015;42(5):515-528.
    1. 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.
    1. 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.
    1. Stein-Thoeringer CK, Nichols KB, Lazrak A, et al. . Lactose drives Enterococcus expansion to promote graft-versus-host disease. Science. 2019;366(6469):1143-1149.
    1. Holler E, Butzhammer P, Schmid 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-versushost disease. Biol Blood Marrow Transplant. 2014;20(5):640-645.
    1. Biagi E, Zama D, Rampelli S, et al. . Early gut microbiota signature of aGvHD in children given allogeneic hematopoietic cell transplantation for hematological disorders. BMC Med Genomics. 2019;12(1):49.
    1. Ilett EE, Jorgensen M, Noguera-Julian M, et al. . Associations of the gut microbiome and clinical factors with acute GVHD in allogeneic HSCT recipients. Blood Adv. 2020;4(22):5797-5809.
    1. Payen M, Nicolis I, Robin M, et al. . Functional and phylogenetic alterations in gut microbiome are linked to graft-versushost disease severity. Blood Adv. 2020;4(9):1824-1832.
    1. 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):902-910.
    1. Varelias A, Ormerod KL, Bunting MD, et al. . Acute graft-versus-host disease is regulated by an IL-17-sensitive microbiome. Blood. 2017;129(15):2172-2185.
    1. Koyama M, Mukhopadhyay P, Schuster IS, 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(5):885-898.
    1. Eriguchi Y, Takashima S, Oka H, et al. . Graftversus- host disease disrupts intestinal microbial ecology by inhibiting Paneth cell production of alpha-defensins. Blood. 2012;120(1):223-231.
    1. Peled JU, Devlin SM, Staffas A, et al. . Intestinal microbiota and relapse after hematopoietic-cell transplantation. J Clin Oncol. 2017;35(15):1650-1659.
    1. Harris B, Morjaria SM, Littmann ER, et al. . Gut microbiota predict pulmonary infiltrates after allogeneic hematopoietic cell transplantation. Am J Respir Crit Care Med. 2016;194(4):450-463.
    1. Haak BW, Littmann ER, Chaubard JL, et al. . Impact of gut colonization with butyrateproducing microbiota on respiratory viral infection following allo-HCT. Blood. 2018;131(26):2978-2986.
    1. Markey KA, Schluter J, Gomes ALC, et al. . The microbe-derived short-chain fatty acids butyrate and propionate are associated with protection from chronic GVHD. Blood. 2020;136(1):130-136.
    1. Tamburini FB, Andermann TM, Tkachenko E, Senchyna F, Banaei N, Bhatt AS. Precision identification of diverse bloodstream pathogens in the gut microbiome. Nat Med. 2018;24(12):1809-1814.
    1. Steck N, Hoffmann M, Sava IG, et al. . Enterococcus faecalis metalloprotease compromises epithelial barrier and contributes to intestinal inflammation. Gastroenterology. 2011;141(3):959-971.
    1. Molina MA, Diaz AM, Hesse C, et al. . Immunostimulatory effects triggered by Enterococcus faecalis CECT7121 probiotic strain involve activation of dendritic cells and interferon-gamma production. PLoS One. 2015;10(5):e0127262.
    1. Ubeda C, Bucci V, Caballero S, et al. . Intestinal microbiota containing Barnesiella species cures vancomycin-resistant Enterococcus faecium colonization. Infect Immun. 2013;81(3):965-973.
    1. Le Roy T, Debedat J, Marquet F, et al. . Comparative evaluation of microbiota engraftment following fecal microbiota transfer in mice models: age, kinetic and microbial status matter. Front Microbiol. 2018;9:3289.
    1. Smillie CS, Sauk J, Gevers D, et al. . Strain tracking reveals the determinants of bacterial engraftment in the human gut following fecal microbiota transplantation. Cell Host Microbe. 2018;23(2):229-240.
    1. Hall AB, Tolonen AC, Xavier RJ. Human genetic variation and the gut microbiome in disease. Nat Rev Genet. 2017;18(11):690-699.
    1. Abt MC, Buffie CG, Susac B, et al. . TLR-7 activation enhances IL-22-mediated colonization resistance against vancomycinresistant enterococcus. Sci Transl Med. 2016;8(327):327ra325.
    1. Derrien M, Van Baarlen P, Hooiveld G, Norin E, Muller M, de Vos WM. Modulation of mucosal immune response, tolerance, and proliferation in mice colonized by the mucin-degrader Akkermansia muciniphila. Front Microbiol. 2011;2:166.
    1. Earle KA, Billings G, Sigal M, et al. . Quantitative imaging of gut microbiota spatial organization. Cell Host Microbe. 2015;18(4):478-488.
    1. Ara T, Hashimoto D, Hayase E, et al. . Intestinal goblet cells protect against GVHD after allogeneic stem cell transplantation via Lypd8. Sci Transl Med. 2020;12(550): eaaw0720.
    1. Mathewson ND, Jenq R, Mathew AV, et al. . Gut microbiome-derived metabolites modulate intestinal epithelial cell damage and mitigate graft-versus-host disease. Nat Immunol. 2016;17(5):505-513.
    1. Swimm A, Giver CR, DeFilipp Z, et al. . Indoles derived from intestinal microbiota act via type I interferon signaling to limit graft-versus-host disease. Blood. 2018;132(23):2506-2519.
    1. Fujiwara H, Docampo MD, Riwes M, et al. . Microbial metabolite sensor GPR43 controls severity of experimental GVHD. Nat Commun. 2018;9(1):3674.
    1. Kaiko GE, Ryu SH, Koues OI, et al. . The Colonic Crypt Protects Stem Cells from Microbiota-Derived Metabolites. Cell. 2016;165(7):1708-1720.
    1. Hanash AM, Dudakov JA, Hua G, et al. . Interleukin-22 protects intestinal stem cells from immune-mediated tissue damage and regulates sensitivity to graft versus host disease. Immunity. 2012;37(2):339-350.
    1. Couturier M, Lamarthee B, Arbez J, et al. . IL- 22 deficiency in donor T cells attenuates murine acute graft-versus-host disease mortality while sparing the graft-versusleukemia effect. Leukemia. 2013;27(7):1527-1537.
    1. Joo E, Yamane S, Hamasaki A, et al. . Enteral supplement enriched with glutamine, fiber, and oligosaccharide attenuates experimental colitis in mice. Nutrition. 2013;29(3):549-555.
    1. Burrello C, Garavaglia F, Cribiu FM, et al. . Therapeutic faecal microbiota transplantation controls intestinal inflammation through IL10 secretion by immune cells. Nat Commun. 2018;9(1):5184.
    1. Atarashi K, Tanoue T, Oshima K, et al. . Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature. 2013;500(7461):232-236.
    1. Campbell C, McKenney PT, Konstantinovsky D, et al. . Bacterial metabolism of bile acids promotes generation of peripheral regulatory T cells. Nature. 2020;581(7809):475-479.
    1. Hang S, Paik D, Yao L, et al. . Bile acid metabolites control TH17 and Treg cell differentiation. Nature. 2019;576(7785):143-148.
    1. Reikvam H, Gronningsaeter IS, Mosevoll KA, Lindas R, Hatfield K, Bruserud O. Patients with treatment-requiring chronic graft versus host disease after allogeneic stem cell transplantation have altered metabolic profiles due to the disease and immunosuppressive therapy: potential implication for biomarkers. Front Immunol. 2017;8:1979.
    1. Michonneau D, Latis E, Curis E, et al. . Metabolomics analysis of human acute graft-versus-host disease reveals changes in host and microbiota-derived metabolites. Nat Commun. 2019;10(1):5695.
    1. Joshi NM, Hassan S, Jasani P, et al. . Bile acid malabsorption in patients with graft-versushost disease of the gastrointestinal tract. Br J Haematol. 2012;157(3):403-407.
    1. Ruutu T, Juvonen E, Remberger M, et al. . Improved survival with ursodeoxycholic acid prophylaxis in allogeneic stem cell transplantation: long-term follow-up of a randomized study. Biol Blood Marrow Transplant. 2014;20(1):135-138.
    1. Webb BJ, Brunner A, Lewis J, Ford CD, Lopansri BK. Repurposing an old drug for a new epidemic: ursodeoxycholic acid to prevent recurrent Clostridioides difficile infection. Clin Infect Dis. 2019;68(3):498-500.
    1. Weber D, Oefner PJ, Dettmer K, et al. . Rifaximin preserves intestinal microbiota balance in patients undergoing allogeneic stem cell transplantation. Bone Marrow Transplant. 2016;51(8):1087-1092.
    1. Rearigh L, Stohs E, Freifeld A, Zimmer A. De-escalation of empiric broad spectrum antibiotics in hematopoietic stem cell transplant recipients with febrile neutropenia. Ann Hematol. 2020;99(8):1917-1924.
    1. Kaleko M, Bristol JA, Hubert S, 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. 2016;41:58-67.
    1. de Gunzburg J, Ghozlane A, Ducher A, et al. . Protection of the human gut microbiome from antibiotics. J Infect Dis. 2018;217(4): 628-636.
    1. Yoshifuji K, Inamoto K, Kiridoshi Y, et al. . Prebiotics protect against acute graft-versushost disease and preserve the gut microbiota in stem cell transplantation. Blood Adv. 2020;4(19):4607-4617.
    1. Iyama S, Sato T, Tatsumi H, et al. . Efficacy of enteral supplementation enriched with glutamine, fiber, and oligosaccharide on mucosal injury following hematopoietic stem cell transplantation. Case Rep Oncol. 2014;7(3): 692-699.
    1. Ladas EJ, Bhatia M, Chen L, et al. . The safety and feasibility of probiotics in children and adolescents undergoing hematopoietic cell transplantation. Bone Marrow Transplant. 2016;51(2):262-266.
    1. Sadanand A, Newland JG, Bednarski JJ. Safety of probiotics among high-risk pediatric hematopoietic stem cell transplant recipients. Infect Dis Ther. 2019;8(2):301-306.
    1. Gerbitz A, Schultz M, Wilke A, et al. . Probiotic effects on experimental graft-versus- host disease: let them eat yogurt. Blood. 2004;103(11):4365-4367.
    1. Le Bastard Q, Ward T, Sidiropoulos D, et al. . Fecal microbiota transplantation reverses antibiotic and chemotherapy-induced gut dysbiosis in mice. Sci Rep. 2018;8(1):6219.
    1. Battipaglia G, Malard F, Rubio MT, et al. . Fecal microbiota transplantation before or after allogeneic hematopoietic transplantation in patients with hematologic malignancies carrying multidrug-resistance bacteria. Haematologica. 2019;104(8):1682-1688.
    1. Innes AJ, Mullish BH, Fernando F, et al. . Faecal microbiota transplant: a novel biological approach to extensively drug-resistant organism- related non-relapse mortality. Bone Marrow Transplant. 2017;52(10):1452-1454.
    1. Kolodziejczyk AA, Zheng D, Elinav E. Dietmicrobiota interactions and personalized nutrition. Nat Rev Microbiol. 2019;17(12): 742-753.
    1. Li X, Lin Y, Li X, et al. . Tyrosine supplement ameliorates murine aGVHD by modulation of gut microbiome and metabolome. EBioMedicine. 2020;61:103048.
    1. D'Amico F, Biagi E, Rampelli S, et al. . Enteral nutrition in pediatric patients undergoing hematopoietic SCT promotes the recovery of gut microbiome homeostasis. Nutrients. 2019;11(12):2958.
    1. 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.
    1. Gonzales F, Bruno B, Alarcon Fuentes M, et al. . Better early outcome with enteral rather than parenteral nutrition in children undergoing MAC allo-SCT. Clin Nutr. 2018;37(6 Pt A):2113-2121.
    1. Beckerson J, Szydlo RM, Hickson M, et al. . Impact of route and adequacy of nutritional intake on outcomes of allogeneic haematopoietic cell transplantation for haematologic malignancies. Clin Nutr. 2019;38(2):738-744.
    1. Segal L, Opie RS. A nutrition strategy to reduce the burden of diet related disease: access to dietician services must complement population health approaches. Front Pharmacol. 2015;6:160.
    1. Johnson AJ, Vangay P, Al-Ghalith GA, et al. . Daily sampling reveals personalized dietmicrobiome associations in humans. Cell Host Microbe. 2019;25(6):789-802.
    1. McFarland LV. Use of probiotics to correct dysbiosis of normal microbiota following disease or disruptive events: a systematic review. BMJ Open. 2014;4(8):e005047.
    1. Suez J, Zmora N, Zilberman-Schapira G, et al. . Post-antibiotic gut mucosal microbiome reconstitution Is impaired by probiotics and improved by autologous FMT. Cell. 2018;174(6):1406-1423.
    1. Cohen SA, Woodfield MC, Boyle N, Stednick Z, Boeckh M, Pergam SA. Incidence and outcomes of bloodstream infections among hematopoietic cell transplant recipients from species commonly reported to be in over-the-counter probiotic formulations. Transpl Infect Dis. 2016;18(5):699-705.
    1. Ambesh P, Stroud S, Franzova E, et al. . Recurrent Lactobacillus bacteremia in a patient with leukemia. J Investig Med High Impact Case Rep. 2017;5(4): 2324709617744233.
    1. 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. 2013;48(3):461-462.
    1. Salminen MK, Rautelin H, Tynkkynen S, et al. . Lactobacillus bacteremia, clinical significance, and patient outcome, with special focus on probiotic L. rhamnosus GG. Clin Infect Dis. 2004;38(1):62-69.
    1. Vahabnezhad E, Mochon AB, Wozniak LJ, Ziring DA. Lactobacillus bacteremia associated with probiotic use in a pediatric patient with ulcerative colitis. J Clin Gastroenterol. 2013;47(5):437-439.
    1. Robin F, Paillard C, Marchandin H, Demeocq F, Bonnet R, Hennequin C. Lactobacillus rhamnosus meningitis following recurrent episodes of bacteremia in a child undergoing allogeneic hematopoietic stem cell transplantation. J Clin Microbiol. 2010;48(11):4317-4319.
    1. Gorshein E, Wei C, Ambrosy S, et al. . Lactobacillus rhamnosus GG probiotic enteric regimen does not appreciably alter the gut microbiome or provide protection against GVHD after allogeneic hematopoietic stem cell transplantation. Clin Transplant. 2017;31(5).
    1. DeFilipp Z, Peled JU, Li S, et al. . Third-party fecal microbiota transplantation following allo-HCT reconstitutes microbiome diversity. Blood Adv. 2018;2(7):745-753.
    1. Bilinski J, Grzesiowski P, Sorensen N, et al. . Fecal microbiota transplantation in patients with blood disorders inhibits gut colonization with antibiotic-resistant bacteria: results of a prospective, single-center study. Clin Infect Dis. 2017;65(3):364-370.
    1. Neemann K, Eichele DD, Smith PW, Bociek R, Akhtari M, Freifeld A. Fecal microbiota transplantation for fulminant Clostridium difficile infection in an allogeneic stem cell transplant patient. Transpl Infect Dis. 2012;14(6):E161-165.
    1. de Castro CG, Ganc AJ, Ganc RL, Petrolli MS, Hamerschlack N. Fecal microbiota transplant after hematopoietic SCT: report of a successful case. Bone Marrow Transplant. 2015;50(1):145.
    1. Mittal C, Miller N, Meighani A, Hart BR, John A, Ramesh M. Fecal microbiota transplant for recurrent Clostridium difficile infection after peripheral autologous stem cell transplant for diffuse large B-cell lymphoma. Bone Marrow Transplant. 2015;50(7):1010.
    1. Webb BJ, Brunner A, Ford CD, Gazdik MA, Petersen FB, Hoda D. Fecal microbiota transplantation for recurrent Clostridium difficile infection in hematopoietic stem cell transplant recipients. Transpl Infect Dis. 2016;18(4):628-633.
    1. Bluestone H, Kronman MP, Suskind DL. Fecal microbiota transplantation for recurrent Clostridium difficile infections in pediatric hematopoietic stem cell transplant recipients. J Pediatric Infect Dis Soc. 2018;7(1):e6-e8.
    1. Moss EL, Falconer SB, Tkachenko E, et al. . Long-term taxonomic and functional divergence from donor bacterial strains following fecal microbiota transplantation in immunocompromised patients. PLoS One. 2017;12(8):e0182585.
    1. Kakihana K, Fujioka Y, Suda W, et al. . Fecal microbiota transplantation for patients with steroid-resistant acute graft-versus-host disease of the gut. Blood. 2016;128(16):2083-2088.
    1. Spindelboeck W, Schulz E, Uhl B, et al. . Repeated fecal microbiota transplantations attenuate diarrhea and lead to sustained changes in the fecal microbiota in acute, refractory gastrointestinal graft-versus-hostdisease. Haematologica. 2017;102(5):e210-e213.
    1. Qi X, Li X, Zhao Y, et al. . Treating steroid refractory intestinal acute graft-vs.-host disease with fecal microbiota transplantation: a pilot study. Front Immunol. 2018;9:2195.
    1. Kaito S, Toya T, Yoshifuji K, et al. . Fecal microbiota transplantation with frozen capsules for a patient with refractory acute gut graft-versus-host disease. Blood Adv. 2018;2(22):3097-3101.
    1. van Lier YF, Davids M, Haverkate NJE, et al. . Donor fecal microbiota transplantation ameliorates intestinal graft-versus-host disease in allogeneic hematopoietic cell transplant recipients. Sci Transl Med. 2020;12(556): eaaz8926.
    1. DeFilipp Z, Bloom PP, Torres Soto M, et al. . Drug-Resistant E. coli bacteremia transmitted by fecal microbiota transplant. N Engl J Med. 2019;381(21):2043-2050.
    1. Bilinski J, Lis K, Tomaszewska A, et al. . Eosinophilic gastroenteritis and graft-versushost disease induced by transmission of Norovirus with fecal microbiota transplant. Transpl Infect Dis. 2021;23(1):e13386.
    1. Cammarota G, Ianiro G, Tilg H, et al. . European consensus conference on faecal microbiota transplantation in clinical practice. Gut. 2017;66(4):569-580.
    1. Golob JL, DeMeules MM, Loeffelholz T, et al. . Butyrogenic bacteria after acute graft-versus- host disease (GVHD) are associated with the development of steroid-refractory GVHD. Blood Adv. 2019;3(19):2866-2869.
    1. Zmora N, Zilberman-Schapira G, Suez J, et al. . Personalized gut mucosal colonization resistance to empiric probiotics is associated with unique host and microbiome features. Cell. 2018;174(6):1388-1405.e21.
    1. Ott SJ, Waetzig GH, Rehman A, et al. . Efficacy of sterile fecal filtrate transfer for treating patients with Clostridium difficile infection. Gastroenterology. 2017;152(4): 799-811.
    1. Han L, Zhang H, Chen S, et al. . Intestinal microbiota can predict acute graft-versushost disease following allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2019;25(10): 1944-1955.
    1. 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.

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