1,195
Views
2
CrossRef citations to date
0
Altmetric
Review

Fecal microbiota transplantation in hematopoietic cell transplant and cellular therapy recipients: lessons learned and the path forward

&
Article: 2229567 | Received 22 Apr 2023, Accepted 21 Jun 2023, Published online: 29 Jun 2023

References

  • Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI. The human microbiome project. Nature. 2007;449(7164):804–18. doi: 10.1038/nature06244.
  • Backhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI. Host-bacterial mutualism in the human intestine. Science. 2005;307(5717):1915–1920. doi: 10.1126/science.1104816.
  • Kim S, Covington A, Pamer EG. The intestinal microbiota: antibiotics, colonization resistance, and enteric pathogens. Immunol Rev. 2017;279(1):90–105. doi: 10.1111/imr.12563.
  • Crawford PA, Gordon JI. Microbial regulation of intestinal radiosensitivity. Proc Natl Acad Sci USA. 2005;102(37):13254–13259. doi: 10.1073/pnas.0504830102.
  • Guo H, Chou W-C, Lai Y, Liang K, Tam JW, Brickey WJ, Chen L, Montgomery ND, Li X, Bohannon LM, et al. Multi-omics analyses of radiation survivors identify radioprotective microbes and metabolites. Science. 2020;370(6516):eaay9097. doi: 10.1126/science.aay9097.
  • Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T, Karaoz U, Wei D, Goldfarb KC, Santee CA, Lynch SV, et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell. 2009;139(3):485–498. doi: 10.1016/j.cell.2009.09.033.
  • Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, Bohlooly-Y M, Glickman JN, Garrett WS. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013;341(6145):569–573. doi: 10.1126/science.1241165.
  • Diener C, Dai CL, Wilmanski T, Baloni P, Smith B, Rappaport N, Hood L, Magis AT, Gibbons SM. Genome–microbiome interplay provides insight into the determinants of the human blood metabolome. Nat Metab. 2022;4(11):1560–1572. doi: 10.1038/s42255-022-00670-1.
  • Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444(7122):1027–1031. doi: 10.1038/nature05414.
  • Radjabzadeh D, Bosch JA, Uitterlinden AG, Zwinderman AH, Ikram MA, van Meurs JBJ, Luik AI, Nieuwdorp M, Lok A, van Duijn CM, et al. Gut microbiome-wide association study of depressive symptoms. Nat Commun. 2022;13(1):7128. doi: 10.1038/s41467-022-34502-3.
  • Qin J, Li Y, Cai Z, Li S, Zhu J, Zhang F, Liang S, Zhang W, Guan Y, Shen D, et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature. 2012;490(7418):55–60. doi: 10.1038/nature11450.
  • Morais LH, Schreiber HL, Mazmanian SK. The gut microbiota–brain axis in behaviour and brain disorders. Nat Rev Microbiol. 2020;19(4):241–255. doi: 10.1038/s41579-020-00460-0.
  • Dang AT, Marsland BJ. Microbes, metabolites, and the gut–lung axis. Mucosal Immunol. 2019;12(4):843–850. doi: 10.1038/s41385-019-0160-6.
  • Yang T, Richards EM, Pepine CJ, Raizada MK. The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease. Nat Rev Nephrol. 2018;14(7):442–456. doi: 10.1038/s41581-018-0018-2.
  • Fu Y-Y, Egorova A, Sobieski C, Kuttiyara J, Calafiore M, Takashima S, Clevers H, Hanash AM. T cell recruitment to the intestinal stem cell compartment drives immune-mediated intestinal damage after allogeneic transplantation. Immunity. 2019;51(1):90–103.e3. doi: 10.1016/j.immuni.2019.06.003.
  • Zeiser R, Blazar BR, Longo DL. Acute graft-versus-host disease — biologic process, prevention, and therapy. N Engl J Med. 2017;377(22):2167–2179. doi: 10.1056/NEJMra1609337.
  • Socié G, Kean LS, Zeiser R, Blazar BR. Insights from integrating clinical and preclinical studies advance understanding of graft-versus-host disease. J Clin Invest. 2021;131(12):e149296. doi: 10.1172/JCI149296.
  • Schwab L, Goroncy L, Palaniyandi S, Gautam S, Triantafyllopoulou A, Mocsai A, Reichardt W, Karlsson FJ, Radhakrishnan SV, Hanke K, et al. Neutrophil granulocytes recruited upon translocation of intestinal bacteria enhance graft-versus-host disease via tissue damage. Nat Med. 2014;20(6):648–654. doi: 10.1038/nm.3517.
  • Hülsdünker J, Ottmüller KJ, Neeff HP, Koyama M, Gao Z, Thomas OS, Follo M, Al-Ahmad A, Prinz G, Duquesne S, et al. Neutrophils provide cellular communication between ileum and mesenteric lymph nodes at graft-versus-host disease onset. Blood. 2018;131(16):1858–1869. doi: 10.1182/blood-2017-10-812891.
  • Koyama M, Mukhopadhyay P, Schuster IS, Henden AS, Hülsdünker J, Varelias A, Vetizou M, Kuns RD, Robb RJ, Zhang P, 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):885–98.e7. doi: 10.1016/j.immuni.2019.08.011.
  • June CH, Sadelain M. Chimeric antigen receptor therapy. N Engl J Med. 2018;379(1):64–73. doi: 10.1056/NEJMra1706169.
  • Walters KE, Martiny JBH, Nabout JC. Alpha-, beta-, and gamma-diversity of bacteria varies across habitats. PLoS One. 2020;15(9):e0233872. doi: 10.1371/journal.pone.0233872.
  • Peled JU, Gomes ALC, Devlin SM, Littmann ER, Taur Y, Sung AD, Weber D, Hashimoto D, Slingerland AE, Slingerland JB, et al. Microbiota as predictor of mortality in allogeneic hematopoietic-cell transplantation. N Engl J Med. 2020;382(9):822–834. doi: 10.1056/NEJMoa1900623.
  • Rashidi A, Maeser D, Kaiser T, Ebadi M, Rehman TU, Holtan SG, Weisdorf DJ, Khoruts A, Staley C. Microbiome swings with repeated insults. Br J Haematol. 2020;189(3):e94–6. doi: 10.1111/bjh.16509.
  • Rashidi A, Kaiser T, Holtan SG, Weisdorf DJ, Khoruts A, Staley C. Pre-transplant recovery of microbiome diversity without recovery of the original microbiome. Bone Marrow Transplant. 2019;54(7):1115–1117. doi: 10.1038/s41409-018-0414-z.
  • Rashidi A, Kaiser T, Graiziger C, Holtan SG, Rehman TU, Weisdorf DJ, Dunny GM, Khoruts A, Staley C. Gut dysbiosis during antileukemia chemotherapy versus allogeneic hematopoietic cell transplantation. Cancer. 2020;126(7):1434–1447. doi: 10.1002/cncr.32641.
  • Ingham AC, Kielsen K, Mordhorst H, Ifversen M, Aarestrup FM, Müller KG, Pamp SJ. Microbiota long-term dynamics and prediction of acute graft-versus-host disease in pediatric allogeneic stem cell transplantation. Microbiome. 2021;9(1):148. doi: 10.1186/s40168-021-01100-2.
  • Ilett EE, Jørgensen M, Noguera-Julian M, Nørgaard JC, Daugaard G, Helleberg M, Paredes R, Murray DD, Lundgren J, MacPherson C, et al. Associations of the gut microbiome and clinical factors with acute GVHD in allogeneic HSCT recipients. Blood Adv. 2020;4(22):5797–5809. doi: 10.1182/bloodadvances.2020002677.
  • Weber D, Hiergeist A, Weber M, Dettmer K, Wolff D, Hahn J, Herr W, Gessner A, Holler E. Detrimental effect of broad-spectrum antibiotics on intestinal microbiome diversity in patients after allogeneic stem cell transplantation: lack of commensal sparing antibiotics. Clin Infect Dis. 2019;68(8):1303–1310. doi: 10.1093/cid/ciy711.
  • Weber D, Oefner PJ, Hiergeist A, Koestler J, Gessner A, Weber M, Hahn J, Wolff D, Stämmler F, Spang R, 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. doi: 10.1182/blood-2015-04-638858.
  • Holler E, Butzhammer P, Schmid K, Hundsrucker C, Koestler J, Peter K, Zhu W, Sporrer D, Hehlgans T, Kreutz M, et al. Metagenomic analysis of the stool microbiome in patients receiving allogeneic stem cell transplantation: loss of diversity is associated with use of systemic antibiotics and more pronounced in gastrointestinal graft-versus-host disease. Biol Blood Marrow Transplant. 2014;20(5):640–645. doi: 10.1016/j.bbmt.2014.01.030.
  • Stein-Thoeringer CK, Nichols KB, Lazrak A, Docampo MD, Slingerland AE, Slingerland JB, Clurman AG, Armijo G, Gomes ALC, Shono Y, et al. Lactose drives Enterococcus expansion to promote graft-versus-host disease. Science. 2019;366(6469):1143–1149. doi: 10.1126/science.aax3760.
  • Taur Y, Xavier JB, Lipuma L, Ubeda C, Goldberg J, Gobourne A, Lee YJ, Dubin KA, Socci ND, Viale A, 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. doi: 10.1093/cid/cis580.
  • van den Brink MRM, Taur Y, Pamer EG. Diversification and evolution of vancomycin-resistant Enterococcus faecium during intestinal domination. Infection. 2019;87(7):e00102–19. doi: 10.1128/IAI.00102-19.
  • Biagi E, Zama D, Nastasi C, Consolandi C, Fiori J, Rampelli S, Turroni S, Centanni M, Severgnini M, Peano C, et al. Gut microbiota trajectory in pediatric patients undergoing hematopoietic SCT. Bone Marrow Transplant. 2015;50(7):992–998. doi: 10.1038/bmt.2015.16.
  • Hino A, Fukushima K, Kusakabe S, Ueda T, Sudo T, Fujita J, Motooka D, Takeda AK, Shinozaki NO, Watanabe S, et al. Prolonged gut microbial alterations in post-transplant survivors of allogeneic haematopoietic stem cell transplantation. Br J Haematol. 2023;201(4):725–737. doi: 10.1111/bjh.18574.
  • Hayase E, Hayase T, Jamal MA, Miyama T, Chang C-C, Ortega MR, Ahmed SS, Karmouch JL, Sanchez CA, Brown AN, et al. Mucus-degrading Bacteroides link carbapenems to aggravated graft-versus-host disease. Cell. 2022;185(20):3705–19.e14. doi: 10.1016/j.cell.2022.09.007.
  • Shono Y, Docampo MD, Peled JU, Perobelli SM, Velardi E, Tsai JJ, Slingerland AE, Smith OM, Young LF, Gupta J, 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):339ra71. doi: 10.1126/scitranslmed.aaf2311.
  • Elgarten CW, Li Y, Getz KD, Hemmer M, Huang Y-S, Hall M, Wang T, Kitko CL, Jagasia MH, Nishihori T, et al. Broad-spectrum antibiotics and risk of graft-versus-host disease in pediatric patients undergoing transplantation for acute leukemia: association of carbapenem use with the risk of acute graft-versus-host disease. Transplant Cell Ther. 2021;27(2):.e177.1–.e177.8. doi: 10.1016/j.jtct.2020.10.012.
  • Lee S-E, Lim J-Y, Ryu D-B, Kim TW, Park SS, Jeon Y-W, Yoon J-H, Cho B-S, Eom K-S, Kim Y-J, 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. doi: 10.1016/j.bbmt.2019.06.001.
  • Tanaka JS, Young RR, Heston SM, Jenkins K, Spees LP, Sung AD, Corbet K, Thompson JC, Bohannon L, Martin PL, et al. Anaerobic antibiotics and the risk of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2020;26(11):2053–2060. doi: 10.1016/j.bbmt.2020.07.011.
  • Hidaka D, Hayase E, Shiratori S, Hasegawa Y, Ishio T, Tateno T, Okada K, Goto H, Sugita J, Onozawa M, et al. The association between the incidence of intestinal graft-vs-host disease and antibiotic use after allogeneic hematopoietic stem cell transplantation. Clin Transplant. 2018;32(9):e13361. doi: 10.1111/ctr.13361.
  • Hanks CR, Slain D, Kanate AS, Wen S, Cumpston A. Impact of anti-anaerobic antibiotic activity on graft-versus-host disease in allogeneic hematopoietic stem cell transplant (HSCT) recipients at an institution that utilizes antibiotic cycling. Transpl Infect Dis. 2021;23(4):e13676. doi: 10.1111/tid.13676.
  • Shouval R, Waters NR, Gomes ALC, Zuanelli Brambilla C, Fei T, Devlin SM, Nguyen CL, Markey KA, Dai A, Slingerland JB, et al. Conditioning regimens are associated with distinct patterns of microbiota injury in allogeneic hematopoietic cell transplantation. Clin Cancer Res. 2023;29(1):165–173. doi: 10.1158/1078-0432.CCR-22-1254.
  • Andersen S, Staudacher H, Weber N, Kennedy G, Varelias A, Banks M, Bauer J. 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. doi: 10.1111/bjh.16218.
  • Schwabkey ZI, Wiesnoski DH, Chang C-C, Tsai W-B, Pham D, Ahmed SS, Hayase T, Ortega Turrubiates MR, El-Himri RK, Sanchez CA, et al. Diet-derived metabolites and mucus link the gut microbiome to fever after cytotoxic cancer treatment. Sci Transl Med. 2022;14(671):eabo3445. doi: 10.1126/scitranslmed.abo3445.
  • D’Amico F, Biagi E, Rampelli S, Fiori J, Zama D, Soverini M, Barone M, Leardini D, Muratore E, Prete A, et al. Enteral nutrition in pediatric patients undergoing hematopoietic sct promotes the recovery of gut microbiome homeostasis. Nutrients. 2019;11(12):11. doi: 10.3390/nu11122958.
  • Zama D, Gori D, Muratore E, Leardini D, Rallo F, Turroni S, Prete A, Brigidi P, Pession A, Masetti R. Enteral versus parenteral nutrition as nutritional support after allogeneic hematopoietic stem cell transplantation: a systematic review and meta-analysis. Transplant Cell Ther. 2021;27(2):e180.1–e180.8. doi: 10.1016/j.jtct.2020.11.006.
  • Nguyen CL, Markey KA, Miltiadous O, Dai A, Waters N, Sadeghi K, Fei T, Shouval R, Taylor BP, Liao C, et al. High-resolution analyses of associations between medications, microbiome, and mortality in cancer patients. Cell. 2023;186(12):2705–18.e17. doi: 10.1016/j.cell.2023.05.007.
  • Zhernakova A, Kurilshikov A, Bonder MJ, Tigchelaar EF, Schirmer M, Vatanen T, Mujagic Z, Vila AV, Falony G, Vieira-Silva S, et al. Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity. Science. 2016;352(6285):565–569. doi: 10.1126/science.aad3369.
  • Falony G, Joossens M, Vieira-Silva S, Wang J, Darzi Y, Faust K, Kurilshikov A, Bonder MJ, Valles-Colomer M, Vandeputte D, et al. Population-level analysis of gut microbiome variation. Science. 2016;352(6285):560–564. doi: 10.1126/science.aad3503.
  • Maier L, Pruteanu M, Kuhn M, Zeller G, Telzerow A, Anderson EE, Brochado AR, Fernandez KC, Dose H, Mori H, et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature. 2018;555(7698):623–628. doi: 10.1038/nature25979.
  • Vich Vila A, Collij V, Sanna S, Sinha T, Imhann F, Bourgonje AR, Mujagic Z, DMAE J, Masclee AAM, Fu J, et al. Impact of commonly used drugs on the composition and metabolic function of the gut microbiota. Nat Commun. 2020;11(1):362. doi: 10.1038/s41467-019-14177-z.
  • Meedt E, Hiergeist A, Gessner A, Dettmer K, Liebisch G, Ghimire S, Poeck H, Edinger M, Wolff D, Herr W, et al. Prolonged suppression of butyrate-producing bacteria is associated with acute gastrointestinal graft-vs-host disease and transplantation-related mortality after allogeneic stem cell transplantation. Clin Infect Dis. 2022;74(4):614–621. doi: 10.1093/cid/ciab500.
  • Golob JL, Pergam SA, Srinivasan S, Fiedler TL, Liu C, Garcia K, Mielcarek M, Ko D, Aker S, Marquis 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. doi: 10.1093/cid/cix699.
  • Legoff J, Resche-Rigon M, Bouquet J, Robin M, Naccache SN, Mercier-Delarue S, Federman S, Samayoa E, Rousseau C, Piron P, et al. The eukaryotic gut virome in hematopoietic stem cell transplantation: new clues in enteric graft-versus-host disease. Nat Med. 2017;23(9):1080–1085. doi: 10.1038/nm.4380.
  • Jenq RR, Ubeda C, Taur Y, Menezes CC, Khanin R, Dudakov JA, Liu C, West ML, Singer NV, Equinda MJ, et al. Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation. J Exp Med. 2012;209(5):903–911. doi: 10.1084/jem.20112408.
  • Burgos da Silva M, Ponce DM, Dai A, Devlin SM, Gomes AL, Moore GF, Slingerland J, Shouval R, Armijo GK, DeWolf S, et al. Preservation of the fecal microbiome is associated with reduced severity of graft-versus-host disease. Blood. 2022;140(22):2385–2397. doi: 10.1182/blood.2021015352.
  • Jenq RR, Taur Y, Devlin SM, Ponce DM, Goldberg JD, Ahr KF, Littmann ER, Ling L, Gobourne AC, Miller LC, et al. Intestinal blautia is associated with reduced death from graft-versus-host disease. Biol Blood Marrow Transplant. 2015;21(8):1373–1383. doi: 10.1016/j.bbmt.2015.04.016.
  • Michonneau D, Latis E, Curis E, Dubouchet L, Ramamoorthy S, Ingram B, de Latour RP, Robin M, de Fontbrune FS, Chevret S, 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. doi: 10.1038/s41467-019-13498-3.
  • Rashidi A, Gao F, Fredricks DN, Pergam SA, Mielcarek M, Milano F, Sandmaier BM, Lee SJ. Analysis of antibiotic exposure and development of acute graft-vs-host disease following allogeneic hematopoietic cell transplantation. JAMA Netw Open. 2023;6:e2317188. doi: 10.1001/jamanetworkopen.2023.17188.
  • Beelen DW, Elmaagacli A, Müller K-D, Hirche H, Schaefer UW. 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 J Am Society Hematol. 1999;93:3267–3275.
  • Chhabra S, Szabo A, Clurman A, McShane K, Waters N, Eastwood D, Samanas L, Fei T, Armijo G, Abedin S, et al. Mitigation of gastrointestinal graft versus host disease with tocilizumab prophylaxis is accompanied by preservation of microbial diversity and attenuation of enterococcal domination. Haemaologica. 2023;108(1):250–256. doi: 10.3324/haematol.2022.281309.
  • Ponce DM, Alousi AM, Nakamura R, Slingerland J, Calafiore M, Sandhu KS, Barker JN, Devlin S, Shia J, Giralt S, et al. A phase 2 study of interleukin-22 and systemic corticosteroids as initial treatment for acute GVHD of the lower GI tract. Blood. 2023;141(12):1389–1401. doi: 10.1182/blood.2021015111.
  • Taur Y, Jenq RR, Perales M-A, Littmann ER, Morjaria S, Ling L, No D, Gobourne A, Viale A, Dahi PB, et al. The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation. Blood. 2014;124(7):1174–1182. doi: 10.1182/blood-2014-02-554725.
  • Ubeda C, Taur Y, Jenq RR, Equinda MJ, Son T, Samstein M, Viale A, Socci ND, van den Brink MRM, Kamboj M, 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. doi: 10.1172/JCI43918.
  • Stoma I, Littmann ER, Peled JU, Giralt S, van den Brink MRM, Pamer EG, Taur Y. Compositional flux within the intestinal microbiota and risk for bloodstream infection with gram-negative bacteria. Clin Infect Dis. 2021;73(11):e4627–35. doi: 10.1093/cid/ciaa068.
  • Schluter J, Peled JU, Taylor BP, Markey KA, Smith M, Taur Y, Niehus R, Staffas A, Dai A, Fontana E, et al. The gut microbiota is associated with immune cell dynamics in humans. Nature. 2020;588(7837):303–307. doi: 10.1038/s41586-020-2971-8.
  • Miltiadous O, Waters NR, Andrlová H, Dai A, Nguyen CL, Burgos da Silva M, Lindner S, Slingerland J, Giardina P, Clurman A, et al. Early intestinal microbial features are associated with CD4 T-cell recovery after allogeneic hematopoietic transplant. Blood J Am Society Hematol. 2022;139(18):2758–2769. doi: 10.1182/blood.2021014255.
  • Haak BW, Littmann ER, Chaubard J-L, Pickard AJ, Fontana E, Adhi F, Gyaltshen Y, Ling L, Morjaria SM, Peled JU, et al. Impact of gut colonization with butyrate-producing microbiota on respiratory viral infection following allo-HCT. Blood. 2018;131:2978–2986. doi: 10.1182/blood-2018-01-828996.
  • Harris B, Morjaria SM, Littmann ER, Geyer AI, Stover DE, Barker JN, Giralt SA, Taur Y, Pamer EG. Gut microbiota predict pulmonary infiltrates after allogeneic hematopoietic cell transplantation. Am J Respir Crit Care Med. 2016;194(4):450–463. doi: 10.1164/rccm.201507-1491OC.
  • Lee YJ, Arguello ES, Jenq RR, Littmann E, Kim GJ, Miller LC, Ling L, Figueroa C, Robilotti E, Perales M-A, et al. Protective factors in the intestinal microbiome against clostridium difficile infection in recipients of allogeneic hematopoietic stem cell transplantation. J Infect Dis. 2017;215(7):1117–1123. doi: 10.1093/infdis/jix011.
  • Markey KA, Schluter J, Gomes ALC, Littmann ER, Pickard AJ, Taylor BP, Giardina PA, Weber D, Dai A, Docampo MD, 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. doi: 10.1182/blood.2019003369.
  • Peled JU, Devlin SM, Staffas A, Lumish M, Khanin R, Littmann ER, Ling L, Kosuri S, Maloy M, Slingerland JB, et al. Intestinal microbiota and relapse after hematopoietic-cell transplantation. J Clin Oncol. 2017;35(15):1650–1659. doi: 10.1200/JCO.2016.70.3348.
  • Smith M, Dai A, Ghilardi G, Amelsberg KV, Devlin SM, Pajarillo R, Slingerland JB, Beghi S, Herrera PS, Giardina P, et al. Gut microbiome correlates of response and toxicity following anti-CD19 CAR T cell therapy. Nat Med. 2022;28(4):713–723. doi: 10.1038/s41591-022-01702-9.
  • Stein-Thoeringer CK, Saini NY, Zamir E, Blumenberg V, Schubert M-L, Mor U, Fante MA, Schmidt S, Hayase E, Hayase T, et al. A non-antibiotic-disrupted gut microbiome is associated with clinical responses to CD19-CAR-T cell cancer immunotherapy. Nat Med. 2023;29(4):906–916. doi: 10.1038/s41591-023-02234-6.
  • Hill GR, Ferrara JLM. 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 J Am Society Hematol. 2000;95(9):2754–2759. doi: 10.1182/blood.V95.9.2754.009k25_2754_2759.
  • Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, deRoos P, Liu H, Cross JR, Pfeffer K, Coffer PJ, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 2013;504(7480):451–455. doi: 10.1038/nature12726.
  • Swimm A, Giver CR, DeFilipp Z, Rangaraju S, Sharma A, Ulezko Antonova A, Sonowal R, Capaldo C, Powell D, Qayed M, 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. doi: 10.1182/blood-2018-03-838193.
  • Wlodarska M, Luo C, Kolde R, d’Hennezel E, Annand JW, Heim CE, Krastel P, Schmitt EK, Omar AS, Creasey EA, et al. Indoleacrylic acid produced by commensal peptostreptococcus species suppresses inflammation. Cell Host & Microbe. 2017;22(1):25–37.e6. doi: 10.1016/j.chom.2017.06.007.
  • Sakata T, von Engelhardt W. Stimulatory effect of short chain fatty acids on the epithelial cell proliferation in rat large intestine. Comp Biochem Physiol A Comp Physiol. 1983;74(2):459–462. doi: 10.1016/0300-9629(83)90631-X.
  • Roediger WE. Utilization of nutrients by isolated epithelial cells of the rat colon. Gastroenterology. 1982;83(2):424–429. doi: 10.1016/S0016-5085(82)80339-9.
  • Bansal T, Alaniz RC, Wood TK, Jayaraman A. The bacterial signal indole increases epithelial-cell tight-junction resistance and attenuates indicators of inflammation. Proc Natl Acad Sci USA. 2010;107(1):228–233. doi: 10.1073/pnas.0906112107.
  • Alexeev EE, Lanis JM, Kao DJ, Campbell EL, Kelly CJ, Battista KD, Gerich ME, Jenkins BR, Walk ST, Kominsky DJ, et al. Microbiota-derived indole metabolites promote human and murine intestinal homeostasis through regulation of interleukin-10 receptor. Am J Pathol. 2018;188(5):1183–1194. doi: 10.1016/j.ajpath.2018.01.011.
  • Saqr A, Carlson B, Staley C, Rashidi A, Al-Kofahi M, Kaiser T, Holtan S, MacMillan M, Young J-A, Jurdi NE, et al. Reduced enterohepatic recirculation of mycophenolate and lower blood concentrations are associated with the stool bacterial microbiome after hematopoietic cell transplantation. Transplant Cell Ther. 2022;28(7):.e372.1–.e372.9. doi: 10.1016/j.jtct.2022.04.018.
  • Hülsdünker J, Thomas OS, Haring E, Unger S, Gonzalo Núñez N, Tugues S, Gao Z, Duquesne S, Cywes-Bentley C, Oyardi O, et al. Immunization against poly-N-acetylglucosamine reduces neutrophil activation and GVHD while sparing microbial diversity. Proc Natl Acad Sci USA. 2019;116(41):20700–20706. doi: 10.1073/pnas.1908549116.
  • Seike K, Kiledal A, Fujiwara H, Henig I, Burgos da Silva M, van den Brink MRM, Hein R, Hoostal M, Liu C, Oravecz-Wilson K, et al. Ambient oxygen levels regulate intestinal dysbiosis and GVHD severity after allogeneic stem cell transplantation. Immunity. 2023;56(2):353–368. doi: 10.1016/j.immuni.2023.01.007.
  • Rashidi A, Ebadi M, Rehman TU, Elhusseini H, Nalluri H, Kaiser T, Ramamoorthy S, Holtan SG, Khoruts A, Weisdorf DJ, et al. Altered microbiota-host metabolic cross talk preceding neutropenic fever in patients with acute leukemia. Blood Adv. 2021;5(20):3937–3950. doi: 10.1182/bloodadvances.2021004973.
  • Rashidi A, Kaiser T, Graiziger C, Holtan SG, Rehman TU, Weisdorf DJ, Khoruts A, Staley C. Specific gut microbiota changes heralding bloodstream infection and neutropenic fever during intensive chemotherapy. Leukemia. 2020;34(1):312–316. doi: 10.1038/s41375-019-0547-0.
  • Desai MS, Seekatz AM, Koropatkin NM, Kamada N, Hickey CA, Wolter M, Pudlo NA, Kitamoto S, Terrapon N, Muller A, et al. A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell. 2016;167(5):1339–53.e21. doi: 10.1016/j.cell.2016.10.043.
  • Ubeda C, Taur Y, Jenq RR, Equinda MJ, Son T, Samstein M, Viale A, Socci ND, van den Brink MRM, Kamboj M, 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. doi: 10.1172/JCI43918.
  • Uribe-Herranz M, Beghi S, Ruella M, Parvathaneni K, Salaris S, Kostopoulos N, George SS, Pierini S, Krimitza E, Costabile F, et al. Modulation of the gut microbiota engages antigen cross-presentation to enhance antitumor effects of CAR T cell immunotherapy. Mol Ther. 2023;31(3):686–700. doi: 10.1016/j.ymthe.2023.01.012.
  • Shono Y, van den Brink MRM. Gut microbiota injury in allogeneic haematopoietic stem cell transplantation. Nat Rev Cancer. 2018;18:283–295. doi: 10.1038/nrc.2018.10.
  • Staffas A, Burgos da Silva M, Slingerland AE, Lazrak A, Bare CJ, Holman CD, Docampo MD, Shono Y, Durham B, Pickard AJ, et al. Nutritional support from the intestinal microbiota improves hematopoietic reconstitution after bone marrow transplantation in mice. Cell Host & Microbe. 2018;23(4):447–57.e4. doi: 10.1016/j.chom.2018.03.002.
  • Andrlová H, Miltiadous O, Kousa AI, Dai A, DeWolf S, Violante S, Park H-Y, Janaki-Raman S, Gardner R, Daker SE, et al. MAIT and Vδ2 unconventional T cells are supported by a diverse intestinal microbiome and correlate with favorable patient outcome after allogeneic HCT. Sci Transl Med. 2022;14(646):eabj2829. doi: 10.1126/scitranslmed.abj2829.
  • Rashidi A, Weisdorf DJ. Microbiota-based approaches to mitigate infectious complications of intensive chemotherapy in patients with acute leukemia. Transl Res. 2020;220:167–181. doi: 10.1016/j.trsl.2020.03.011.
  • Kelly CR, Khoruts A, Staley C, Sadowsky MJ, Abd M, Alani M, Bakow B, Curran P, McKenney J, Tisch A, et al. Effect of fecal microbiota transplantation on recurrence in multiply recurrent clostridium difficile infection: a randomized trial. Ann Intern Med. 2016;165(9):609–616. doi: 10.7326/M16-0271.
  • 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):E161–5. doi: 10.1111/tid.12017.
  • 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;50:145. doi: 10.1038/bmt.2014.212.
  • 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. doi: 10.1111/tid.12550.
  • 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):e6–8. doi: 10.1093/jpids/pix076.
  • Spindelboeck W, Halwachs B, Bayer N, Huber-Krassnitzer B, Schulz E, Uhl B, Gaksch L, Hatzl S, Bachmayr V, Kleissl L, et al. Antibiotic use and ileocolonic immune cells in patients receiving fecal microbiota transplantation for refractory intestinal GvHD: a prospective cohort study. Ther Adv Hematol. 2021;12:20406207211058333. doi: 10.1177/20406207211058333.
  • Goeser F, Sifft B, Stein-Thoeringer C, Farowski F, Strassburg CP, Brossart P, Higgins PG, Scheid C, Wolf D, Holderried TAW, et al. Fecal microbiota transfer for refractory intestinal graft-versus-host disease — Experience from two German tertiary centers. Eur J Haematol. 2021;107(2):229–245. doi: 10.1111/ejh.13642.
  • Battipaglia G, Malard F, Rubio MT, Ruggeri A, Mamez AC, Brissot E, Giannotti F, Dulery R, Joly AC, Baylatry 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. doi: 10.3324/haematol.2018.198549.
  • van Lier YF, Davids M, Haverkate NJE, de Groot PF, Donker ML, Meijer E, Heubel-Moenen FCJI, Nur E, Zeerleder SS, Nieuwdorp M, 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. doi: 10.1126/scitranslmed.aaz8926.
  • DeFilipp Z, Peled JU, Li S, Mahabamunuge J, Dagher Z, Slingerland AE, Del Rio C, Valles B, Kempner ME, Smith M, et al. Third-party fecal microbiota transplantation following allo-HCT reconstitutes microbiome diversity. Blood Adv. 2018;2(7):745–753. doi: 10.1182/bloodadvances.2018017731.
  • Zhao Y, Li X, Zhou Y, Gao J, Jiao Y, Zhu B, Wu D, Qi X. Safety and efficacy of fecal microbiota transplantation for grade iv steroid refractory gi-gvhd patients: interim results from FMT2017002 trial. Front Immunol. 2021;12:678476. doi: 10.3389/fimmu.2021.678476.
  • Rashidi A, Ebadi M, Rehman TU, Elhusseini H, Kazadi D, Halaweish H, Khan MH, Hoeschen A, Cao Q, Luo X, et al. Randomized double-blind phase II trial of fecal microbiota transplantation versus placebo in allogeneic hematopoietic cell transplantation and AML. J Clin Oncol. 2023:JCO2202366. doi: 10.1200/JCO.22.02366
  • Ghani R, Mullish BH, McDonald JAK, Ghazy A, Williams HRT, Brannigan ET, Mookerjee S, Satta G, Gilchrist M, Duncan N, et al. Disease prevention not decolonization: a model for fecal microbiota transplantation in patients colonized with multidrug-resistant organisms. Clin Infect Dis. 2021;72(8):1444–1447. doi: 10.1093/cid/ciaa948.
  • Innes AJ, Mullish BH, Ghani R, Szydlo RM, Apperley JF, Olavarria E, Palanicawandar R, Kanfer EJ, Milojkovic D, McDonald JAK, et al. Fecal microbiota transplant mitigates adverse outcomes seen in patients colonized with multidrug-resistant organisms undergoing allogeneic hematopoietic cell transplantation. Front Cell Infect Microbiol. 2021;11:684659. doi: 10.3389/fcimb.2021.684659.
  • Taur Y, Coyte K, Schluter J, Robilotti E, Figueroa C, Gjonbalaj M, Littmann ER, Ling L, Miller L, Gyaltshen Y, et al. Reconstitution of the gut microbiota of antibiotic-treated patients by autologous fecal microbiota transplant. Sci Transl Med. 2018;10(460):eaap9489. doi: 10.1126/scitranslmed.aap9489.
  • Kakihana K, Fujioka Y, Suda W, Najima Y, Kuwata G, Sasajima S, Mimura I, Morita H, Sugiyama D, Nishikawa H, et al. Fecal microbiota transplantation for patients with steroid-resistant acute graft-versus-host disease of the gut. Blood. 2016;128(16):2083–2088. doi: 10.1182/blood-2016-05-717652.
  • Kaito S, Toya T, Yoshifuji K, Kurosawa S, Inamoto K, Takeshita K, Suda W, Kakihana K, Honda K, Hattori M, 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. doi: 10.1182/bloodadvances.2018024968.
  • Wu S-R, Reddy P. Tissue tolerance: a distinct concept to control acute GVHD severity. Blood. 2017;129(13):1747–1752. doi: 10.1182/blood-2016-09-740431.
  • Köhler N, Zeiser R. Intestinal microbiota influence immune tolerance post allogeneic hematopoietic cell transplantation and intestinal GVHD. Front Immunol. 2018;9:3179. doi: 10.3389/fimmu.2018.03179.
  • Soares MP, Teixeira L, Moita LF. Disease tolerance and immunity in host protection against infection. Nat Rev Immunol. 2017;17(2):83–96. doi: 10.1038/nri.2016.136.
  • DeFilipp Z, Bloom PP, Torres Soto M, Mansour MK, Sater MRA, Huntley MH, Turbett S, Chung RT, Chen Y-B, Hohmann EL. Drug-resistant E. coli bacteremia transmitted by fecal microbiota transplant. N Engl J Med. 2019;381:2043–2050. doi: 10.1056/NEJMoa1910437.
  • Bilinski J, Lis K, Tomaszewska A, Pechcinska A, Grzesiowski P, Dzieciatkowski T, Walesiak A, Gierej B, Ziarkiewicz-Wróblewska B, Tyszka M, et al. Eosinophilic gastroenteritis and graft-versus-host disease induced by transmission of Norovirus with fecal microbiota transplant. Transpl Infect Dis. 2021;23(1):e13386. doi: 10.1111/tid.13386.
  • Eshel A, Sharon I, Nagler A, Bomze D, Danylesko I, Fein JA, Geva M, Henig I, Shimoni A, Zuckerman T, et al. Origins of bloodstream infections following fecal microbiota transplantation: a strain-level analysis. Blood Adv. 2022;6(2):568–573. doi: 10.1182/bloodadvances.2021005110.
  • Rasmussen TS, Koefoed AK, Jakobsen RR, Deng L, Castro-Mejía JL, Brunse A, Neve H, Vogensen FK, Nielsen DS. Bacteriophage-mediated manipulation of the gut microbiome – promises and presents limitations. FEMS Microbiol Rev. 2020;44(4):507–521. doi: 10.1093/femsre/fuaa020.
  • Ott SJ, Waetzig GH, Rehman A, Moltzau-Anderson J, Bharti R, Grasis JA, Cassidy L, Tholey A, Fickenscher H, Seegert D, et al. Efficacy of sterile fecal filtrate transfer for treating patients with clostridium difficile infection. Gastroenterology. 2017;152(4):799–811.e7. doi: 10.1053/j.gastro.2016.11.010.
  • Zhang F, Zuo T, Yeoh YK, Cheng FWT, Liu Q, Tang W, Cheung KCY, Yang K, Cheung CP, Mo CC, et al. Longitudinal dynamics of gut bacteriome, mycobiome and virome after fecal microbiota transplantation in graft-versus-host disease. Nat Commun. 2021;12(1):65. doi: 10.1038/s41467-020-20240-x.
  • Malard F, Vekhoff A, Lapusan S, Isnard F, D’incan-Corda E, Rey J, Saillard C, Thomas X, Ducastelle-Lepretre S, Paubelle E, et al. Gut microbiota diversity after autologous fecal microbiota transfer in acute myeloid leukemia patients. Nat Commun. 2021;12(1):3084. doi: 10.1038/s41467-021-23376-6.
  • Bilinski J, Grzesiowski P, Sorensen N, Madry K, Muszynski J, Robak K, Wroblewska M, Dzieciatkowski T, Dulny G, Dwilewicz-Trojaczek J, 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. doi: 10.1093/cid/cix252.
  • Merli P, Putignani L, Ruggeri A, Del Chierico F, Gargiullo L, Galaverna F, Gaspari S, Pagliara D, Russo A, Pane S, et al. Decolonization of multi-drug resistant bacteria by fecal microbiota transplantation in five pediatric patients before allogeneic hematopoietic stem cell transplantation: gut microbiota profiling, infectious and clinical outcomes. Haematologica. 2020;105(11):2686–2690. doi: 10.3324/haematol.2019.244210.
  • Olesen SW, Leier MM, Alm EJ, Kahn SA. Searching for superstool: maximizing the therapeutic potential of FMT. Nat Rev Gastroenterol Hepatol. 2018;15(7):387–388. doi: 10.1038/s41575-018-0019-4.