Altered intestinal microbiome and epithelial damage aggravate intestinal graft-versus-host disease

References

• Ferrara JL, Levine JE, Reddy P, Holler E. Graft-versus-host disease. Lancet. 2009;373(9674):1550–16. doi:10.1016/S0140-6736(09)60237-3.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Martinez-Cibrian N, Zeiser R, Perez-Simon JA. Graft-versus-host disease prophylaxis: pathophysiology-based review on current approaches and future directions. Blood Rev. 2021;48:100792. doi:10.1016/j.blre.2020.100792.
   PubMed Web of Science ®Google Scholar
• Allaire JM, Crowley SM, Law HT, Chang SY, Ko HJ, Vallance BA. The intestinal epithelium: central coordinator of mucosal immunity. Trends Immunol. 2018;39(9):677–696. doi:10.1016/j.it.2018.04.002.
   PubMed Web of Science ®Google Scholar
• Kayama H, Okumura R, Takeda K. Interaction between the microbiota, epithelia, and immune cells in the intestine. Annu Rev Immunol. 2020;38(1):23–48. doi:10.1146/annurev-immunol-070119-115104.
   PubMed Web of Science ®Google Scholar
• Nalle SC, Turner JR. Intestinal barrier loss as a critical pathogenic link between inflammatory bowel disease and graft-versus-host disease. Mucosal Immunol. 2015;8(4):720–730. doi:10.1038/mi.2015.40.
   PubMed Web of Science ®Google Scholar
• Staffas A, Burgos da Silva M, van den Brink MR. The intestinal microbiota in allogeneic hematopoietic cell transplant and graft-versus-host disease. Blood. 2017;129(8):927–933. doi:10.1182/blood-2016-09-691394.
   PubMed Web of Science ®Google Scholar
• Van Lier YF, Van den Brink MRM, Hazenberg MD, Markey KA. The post-hematopoietic cell transplantation microbiome: relationships with transplant outcome and potential therapeutic targets. Haematologica. 2021;106(8):2042–2053. doi:10.3324/haematol.2020.270835.
   PubMed Web of Science ®Google Scholar
• Toubai T, Magenau J. Immunopathology and biology-based treatment of steroid-refractory graft-versus-host disease. Blood. 2020;136(4):429–440. doi:10.1182/blood.2019000953.
   PubMed Web of Science ®Google Scholar
• Zeiser R, von Bubnoff N, Butler J, Mohty M, Niederwieser D, Or R, Szer J, Wagner EM, Zuckerman T, Mahuzier B, et al. Ruxolitinib for glucocorticoid-refractory acute graft-versus-host disease. N Engl J Med. 2020;382(19):1800–1810. doi:10.1056/NEJMoa1917635.
   PubMed Web of Science ®Google Scholar
• Chakraverty R, Teshima T. Graft-versus-host disease: a disorder of tissue regeneration and repair. Blood. 2021;138(18):1657–1665. doi:10.1182/blood.2021011867.
   PubMed Web of Science ®Google Scholar
• Goudarzi M, Mak TD, Jacobs JP, Moon BH, Strawn SJ, Braun J, Brenner DJ, Fornace AJ, Li H-H. An integrated multi-omic approach to assess radiation injury on the host-microbiome axis. Radiat Res. 2016;186(3):219–234. doi:10.1667/RR14306.1.
   PubMed Web of Science ®Google Scholar
• Gerassy-Vainberg S, Blatt A, Danin-Poleg Y, Gershovich K, Sabo E, Nevelsky A, Daniel S, Dahan A, Ziv O, Dheer R, et al. Radiation induces proinflammatory dysbiosis: transmission of inflammatory susceptibility by host cytokine induction. Gut. 2018;67(1):97–107. doi:10.1136/gutjnl-2017-313789.
   PubMed Web of Science ®Google Scholar
• Li Y, Yan H, Zhang Y, Li Q, Yu L, Li Q, Liu C, Xie Y, Chen K, Ye F, et al. Alterations of the gut microbiome composition and lipid metabolic profile in radiation enteritis. Front Cell Infect Microbiol. 2020;10:541178. doi:10.3389/fcimb.2020.541178.
   PubMed Web of Science ®Google Scholar
• Zhao TS, Xie LW, Cai S, Xu JY, Zhou H, Tang LF, Yang C, Fang S, Li M, Tian Y, et al. Dysbiosis of gut microbiota is associated with the progression of radiation-induced intestinal injury and is alleviated by oral compound probiotics in mouse model. Front Cell Infect Microbiol. 2021;11:717636. doi:10.3389/fcimb.2021.717636.
   PubMed Web of Science ®Google Scholar
• Zhou B, Xia X, Wang P, Chen S, Yu C, Huang R, Zhang R, Wang Y, Lu L, Yuan F, et al. Induction and amelioration of methotrexate-induced gastrointestinal toxicity are related to immune response and gut microbiota. EBioMedicine. 2018;33:122–133. doi:10.1016/j.ebiom.2018.06.029.
   PubMed Web of Science ®Google Scholar
• Huang X, Fang Q, Rao T, Zhou L, Zeng X, Tan Z. Leucovorin ameliorated methotrexate induced intestinal toxicity via modulation of the gut microbiota. Toxicol Appl Pharmacol. 2020;391:114900. doi:10.1016/j.taap.2020.114900.
   PubMed Web of Science ®Google Scholar
• Xu X, Zhang X. Effects of cyclophosphamide on immune system and gut microbiota in mice. Microbiol Res. 2015;171:97–106. doi:10.1016/j.micres.2014.11.002.
   PubMed Web of Science ®Google Scholar
• Cui M, Xiao H, Li Y, Zhou L, Zhao S, Luo D, Zheng Q, Dong J, Zhao Y, Zhang X, et al. Faecal microbiota transplantation protects against radiation-induced toxicity. EMBO Mol Med. 2017;9(4):448–461. doi:10.15252/emmm.201606932.
   PubMed Web of Science ®Google Scholar
• Wang W, Hu L, Chang S, Ma L, Li X, Yang Z, Du C, Qu X, Zhang C, Wang S, et al. Total body irradiation-induced colon damage is prevented by nitrate-mediated suppression of oxidative stress and homeostasis of the gut microbiome. Nitric Oxide. 2020;102:1–11. doi:10.1016/j.niox.2020.05.002.
   PubMed Web of Science ®Google Scholar
• Li M, Gu MM, Lang Y, Shi J, Chen BPC, Guan H. The vanillin derivative VND3207 protects intestine against radiation injury by modulating p53/NOXA signaling pathway and restoring the balance of gut microbiota. Free Radic Biol Med. 2019;145:223–236. doi:10.1016/j.freeradbiomed.2019.09.035.
   PubMed Web of Science ®Google Scholar
• Lu L, Jiang M, Zhu C, He J, Fan S. Amelioration of whole abdominal irradiation-induced intestinal injury in mice with 3,3’-Diindolylmethane (DIM). Free Radic Biol Med. 2019;130:244–255. doi:10.1016/j.freeradbiomed.2018.10.410.
   PubMed Web of Science ®Google Scholar
• Ying M, Yu Q, Zheng B, Wang H, Wang J, Chen S. Cultured Cordyceps sinensis polysaccharides modulate intestinal mucosal immunity and gut microbiota in cyclophosphamide-treated mice. Carbohydr Polym. 2020;235:115957. doi:10.1016/j.carbpol.2020.115957.
   PubMed Web of Science ®Google Scholar
• Hueso T, Ekpe K, Mayeur C, Gatse A, Joncquel-Chevallier Curt M, Gricourt G, Rodriguez C, Burdet C, Ulmann G, Neut C, et al. Impact and consequences of intensive chemotherapy on intestinal barrier and microbiota in acute myeloid leukemia: the role of mucosal strengthening. Gut Microbes. 2020;12(1):1800897. doi:10.1080/19490976.2020.1800897.
   PubMed Web of Science ®Google Scholar
• Rajagopala SV, Yooseph S, Harkins DM, Moncera KJ, Zabokrtsky KB, Torralba MG, Tovchigrechko A, Highlander SK, Pieper R, Sender L, et al. Gastrointestinal microbial populations can distinguish pediatric and adolescent Acute Lymphoblastic Leukemia (ALL) at the time of disease diagnosis. Bmc Genomics. 2016;17(1):635. doi:10.1186/s12864-016-2965-y.
   PubMedGoogle Scholar
• Rajagopala SV, Singh H, Yu Y, Zabokrtsky KB, Torralba MG, Moncera KJ, Frank B, Pieper R, Sender L, Nelson KE, et al. Persistent gut microbial dysbiosis in children with Acute Lymphoblastic Leukemia (ALL) During Chemotherapy. Microb Ecol. 2020;79(4):1034–1043. doi:10.1007/s00248-019-01448-x.
   PubMed Web of Science ®Google Scholar
• Chua LL, Rajasuriar R, Lim YAL, Woo YL, Loke P, Ariffin H. Temporal changes in gut microbiota profile in children with acute lymphoblastic leukemia prior to commencement-, during-, and post-cessation of chemotherapy. Bmc Cancer. 2020;20(1):151. doi:10.1186/s12885-020-6654-5.
   PubMed Web of Science ®Google Scholar
• De Pietri S, Ingham AC, Frandsen TL, Rathe M, Krych L, Castro-Mejia JL, Nielsen DS, Nersting J, Wehner PS, Schmiegelow K, et al. Gastrointestinal toxicity during induction treatment for childhood acute lymphoblastic leukemia: the impact of the gut microbiota. Int J Cancer. 2020;147(7):1953–1962. doi:10.1002/ijc.32942.
   PubMed Web of Science ®Google Scholar
• Hakim H, Dallas R, Wolf J, Tang L, Schultz-Cherry S, Darling V, Johnson C, Karlsson EA, Chang T-C, Jeha S, et al. Gut microbiome composition predicts infection risk during chemotherapy in children with Acute Lymphoblastic Leukemia. Clin Infect Dis. 2018;67(4):541–548. doi:10.1093/cid/ciy153.
   PubMed Web of Science ®Google Scholar
• Zwielehner J, Lassl C, Hippe B, Pointner A, Switzeny OJ, Remely M, Kitzweger E, Ruckser R, Haslberger AG. Changes in human fecal microbiota due to chemotherapy analyzed by TaqMan-PCR, 454 sequencing and PCR-DGGE fingerprinting. PLos One. 2011;6(12):e28654. doi:10.1371/journal.pone.0028654.
   PubMed Web of Science ®Google Scholar
• Montassier E, Batard E, Massart S, Gastinne T, Carton T, Caillon J, Le Fresne S, Caroff N, Hardouin JB, Moreau P, et al. 16S rRNA gene pyrosequencing reveals shift in patient faecal microbiota during high-dose chemotherapy as conditioning regimen for bone marrow transplantation. Microb Ecol. 2014;67(3):690–699. doi:10.1007/s00248-013-0355-4.
   PubMed Web of Science ®Google Scholar
• Montassier E, Gastinne T, Vangay P, Al-Ghalith GA, Bruley des Varannes S, Massart S, Moreau P, Potel G, de La Cochetière MF, Batard E, et al. Chemotherapy-driven dysbiosis in the intestinal microbiome. Aliment Pharmacol Ther. 2015;42(5):515–528. doi:10.1111/apt.13302.
   PubMed Web of Science ®Google Scholar
• van Vliet MJ, Tissing WJ, Dun CA, Meessen NE, Kamps WA, de Bont ES, van Vliet M, de Bont E, Harmsen H. 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. doi:10.1086/599346.
   PubMed Web of Science ®Google Scholar
• Rashidi A, Kaiser T, Shields-Cutler R, Graiziger C, Holtan SG, Rehman TU, Wasko J, Weisdorf DJ, Dunny G, Khoruts A, et al. Dysbiosis patterns during re-induction/salvage versus induction chemotherapy for acute leukemia. Sci Rep. 2019;9(1):6083. doi:10.1038/s41598-019-42652-6.
   PubMedGoogle Scholar
• Guarner F, Malagelada JR. Gut flora in health and disease. Lancet. 2003;361(9356):512–519. doi:10.1016/S0140-6736(03)12489-0.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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). doi:10.1126/scitranslmed.aaf2311.
   PubMed Web of Science ®Google Scholar
• Hayase E, Hayase T, Jamal MA, Miyama T, Chang CC, 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):3705–3719.e14. doi:10.1016/j.cell.2022.09.007.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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 Tr. 2015;21(8):1373–1383. doi:10.1016/j.bbmt.2015.04.016.
   PubMed Web of Science ®Google Scholar
• Lee SE, Lim JY, Ryu DB, Kim TW, Park SS, Jeon YW, 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 Tr. 2019;25(10):1933–1943. doi:10.1016/j.bbmt.2019.06.001.
   PubMed Web of Science ®Google Scholar
• Weber D, Jenq RR, Peled JU, Taur Y, Hiergeist A, Koestler J, Dettmer K, Weber M, Wolff D, Hahn J, 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 Tr. 2017;23(5):845–852. doi:10.1016/j.bbmt.2017.02.006.
   PubMed Web of Science ®Google Scholar
• 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 Tr. 2020;26(11):2053–2060. doi:10.1016/j.bbmt.2020.07.011.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Routy B, Letendre C, Enot D, Chenard-Poirier M, Mehraj V, Seguin NC, Guenda K, Gagnon K, Woerther P-L, Ghez D, et al. The influence of gut-decontamination prophylactic antibiotics on acute graft-versus-host disease and survival following allogeneic hematopoietic stem cell transplantation. Oncoimmunology. 2017;6(1):6. doi:10.1080/2162402X.2016.1258506.
   Web of Science ®Google Scholar
• Simms-Waldrip TR, Sunkersett G, Coughlin LA, Savani MR, Arana C, Kim J, Kim M, Zhan X, Greenberg DE, Xie Y, 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 Tr. 2017;23(5):820–829. doi:10.1016/j.bbmt.2017.02.004.
   PubMed Web of Science ®Google Scholar
• 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):32. doi:10.1111/ctr.13361.
   Web of Science ®Google Scholar
• Nishi K, Kanda J, Hishizawa M, Kitano T, Kondo T, Yamashita K, Takaori-Kondo A. Impact of the use and type of antibiotics on acute graft-versus-host disease. Biol Blood Marrow Tr. 2018;24(11):2178–2183. doi:10.1016/j.bbmt.2018.06.031.
   PubMed Web of Science ®Google Scholar
• Elgarten CW, Li YM, Getz KD, Hemmer M, Huang YSV, 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. Transpl Cell Ther. 2021;27(2):.e177.1–.e177.8. doi:10.1016/j.jtct.2020.10.012.
   Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Kolodziejczyk AA, Zheng D, Elinav E. Diet–microbiota interactions and personalized nutrition. Nat Rev Microbiol. 2019;17(12):742–753. doi:10.1038/s41579-019-0256-8.
   PubMed Web of Science ®Google Scholar
• Zeng X, Xing X, Gupta M, Keber FC, Lopez JG, Lee YJ, Roichman A, Wang L, Neinast MD, Donia MS, et al. Gut bacterial nutrient preferences quantified in vivo. Cell. 2022;185(18):3441–3456.e19. doi:10.1016/j.cell.2022.07.020.
   PubMed Web of Science ®Google Scholar
• Seguy D, Berthon C, Micol JB, Darre S, Dalle JH, Neuville S, Bauters F, Jouet J-P, Yakoub-Agha I. Enteral feeding and early outcomes of patients undergoing allogeneic stem cell transplantation following myeloablative conditioning. Transplantation. 2006;82(6):835–839. doi:10.1097/01.tp.0000229419.73428.ff.
   PubMed Web of Science ®Google Scholar
• Seguy D, Duhamel A, Rejeb MB, Gomez E, Buhl ND, Bruno B, Cortot A, Yakoub-Agha I. Better outcome of patients undergoing enteral tube feeding after myeloablative conditioning for allogeneic stem cell transplantation. Transplantation. 2012;94(3):287–294. doi:10.1097/TP.0b013e3182558f60.
   PubMed Web of Science ®Google Scholar
• Gonzales F, Bruno B, Fuentes MA, De Berranger E, Guimber D, Behal H, Gandemer V, Spiegel A, Sirvent A, Yakoub-Agha I, et al. Better early outcome with enteral rather than parenteral nutrition in children undergoing MAC allo-SCT. Clin Nutr. 2018;37(6):2113–2121. doi:10.1016/j.clnu.2017.10.005.
   PubMed Web of Science ®Google Scholar
• Beckerson J, Szydlo RM, Hickson M, Mactier CE, Innes AJ, Gabriel IH, Palanicawandar R, Kanfer EJ, Macdonald DH, Milojkovic D, 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. doi:10.1016/j.clnu.2018.03.008.
   PubMed Web of Science ®Google Scholar
• Guieze R, Lemal R, Cabrespine A, Hermet E, Tournilhac O, Combal C, Bay J-O, Bouteloup C. Enteral versus parenteral nutritional support in allogeneic haematopoietic stem-cell transplantation. Clin Nutr. 2014;33(3):533–538. doi:10.1016/j.clnu.2013.07.012.
   PubMed Web of Science ®Google Scholar
• 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.
   Web of Science ®Google Scholar
• Yang B, Zhang X, Gong H, Huang Y, Wang C, Liu H, Dong C, Ma S, Wu X, Wu D, et al. High stearic acid diet modulates gut microbiota and aggravates acute graft-versus-host disease. Signal Transduct Target Ther. 2021;6(1):277. doi:10.1038/s41392-021-00600-9.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Khuat LT, Le CT, Pai CS, Shields-Cutler RR, Holtan SG, Rashidi A, Parker SL, Knights D, Luna JI, Dunai C, et al. Obesity induces gut microbiota alterations and augments acute graft-versus-host disease after allogeneic stem cell transplantation. Sci Transl Med. 2020;12(571):12. doi:10.1126/scitranslmed.aay7713.
   Web of Science ®Google Scholar
• Li X, Lin Y, Li X, Xu X, Zhao Y, Xu L, Gao Y, Li Y, Tan Y, Qian P, et al. Tyrosine supplement ameliorates murine aGVHD by modulation of gut microbiome and metabolome. EBioMedicine. 2020;61:103048. doi:10.1016/j.ebiom.2020.103048.
   PubMed Web of Science ®Google Scholar
• Guo H, Chou WC, 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):370. doi:10.1126/science.aay9097.
   Web of Science ®Google Scholar
• Ijiri K, Potten CS. Response of intestinal cells of differing topographical and hierarchical status to ten cytotoxic drugs and five sources of radiation. Br J Cancer. 1983;47(2):175–185. doi:10.1038/bjc.1983.25.
   PubMed Web of Science ®Google Scholar
• Ijiri K, Potten CS. Further studies on the response of intestinal crypt cells of different hierarchical status to eighteen different cytotoxic agents. Br J Cancer. 1987;55(2):113–123. doi:10.1038/bjc.1987.25.
   PubMed Web of Science ®Google Scholar
• Keefe DM, Brealey J, Goland GJ, Cummins AG. Chemotherapy for cancer causes apoptosis that precedes hypoplasia in crypts of the small intestine in humans. Gut. 2000;47(5):632–637. doi:10.1136/gut.47.5.632.
   PubMed Web of Science ®Google Scholar
• Blijlevens NM, Donnelly JP, de Pauw BE. Prospective evaluation of gut mucosal barrier injury following various myeloablative regimens for haematopoietic stem cell transplant. Bone Marrow Transplant. 2005;35(7):707–711. doi:10.1038/sj.bmt.1704863.
   PubMed Web of Science ®Google Scholar
• Hill GR, Crawford JM, Cooke KR, Brinson YS, Pan L, Ferrara JL. Total body irradiation and acute graft-versus-host disease: the role of gastrointestinal damage and inflammatory cytokines. Blood. 1997;90(8):3204–3213. doi:10.1182/blood.V90.8.3204.
   PubMed Web of Science ®Google Scholar
• Johansson JE, Brune M, Ekman T. The gut mucosa barrier is preserved during allogeneic, haemopoietic stem cell transplantation with reduced intensity conditioning. Bone Marrow Transplant. 2001;28(8):737–742. doi:10.1038/sj.bmt.1703230.
   PubMed Web of Science ®Google Scholar
• Johansson JE, Ekman T. Gut toxicity during hemopoietic stem cell transplantation may predict acute graft-versus-host disease severity in patients. Dig Dis Sci. 2007;52(9):2340–2345. doi:10.1007/s10620-006-9404-x.
   PubMed Web of Science ®Google Scholar
• Nalle SC, Zuo L, Ong M, Singh G, Worthylake AM, Choi W, Manresa MC, Southworth AP, Edelblum KL, Baker GJ, et al. Graft-versus-host disease propagation depends on increased intestinal epithelial tight junction permeability. J Clin Invest. 2019;129(2):902–914. doi:10.1172/JCI98554.
   PubMed Web of Science ®Google Scholar
• Martin-Gallausiaux C, Marinelli L, Blottiere HM, Larraufie P, Lapaque N. SCFA: mechanisms and functional importance in the gut. Proc Nutr Soc. 2021;80(1):37–49. doi:10.1017/S0029665120006916.
   PubMed Web of Science ®Google Scholar
• Romick-Rosendale LE, Haslam DB, Lane A, Denson L, Lake K, Wilkey A, Watanabe M, Bauer S, Litts B, Luebbering N, et al. Antibiotic exposure and reduced short chain fatty acid production after hematopoietic stem cell transplant. Biol Blood Marrow Transplant. 2018;24(12):2418–2424. doi:10.1016/j.bbmt.2018.07.030.
   PubMed Web of Science ®Google Scholar
• Payen M, Nicolis I, Robin M, Michonneau D, Delannoye J, Mayeur C, Kapel N, Berçot B, Butel M-J, Le Goff J, et al. Functional and phylogenetic alterations in gut microbiome are linked to graft-versus-host disease severity. Blood Adv. 2020;4(9):1824–1832. doi:10.1182/bloodadvances.2020001531.
   PubMed Web of Science ®Google Scholar
• Mathewson ND, Jenq R, Mathew AV, Koenigsknecht M, Hanash A, Toubai T, Oravecz-Wilson K, Wu S-R, Sun Y, Rossi C, et al. Gut microbiome–derived metabolites modulate intestinal epithelial cell damage and mitigate graft-versus-host disease. Nat Immunol. 2016;17(5):505–513. doi:10.1038/ni.3400.
   PubMed Web of Science ®Google Scholar
• Jia W, Xie G, Jia W. Bile acid–microbiota crosstalk in gastrointestinal inflammation and carcinogenesis. Nat Rev Gastroenterol Hepatol. 2018;15(2):111–128. doi:10.1038/nrgastro.2017.119.
   PubMed Web of Science ®Google Scholar
• Fu T, Coulter S, Yoshihara E, Oh TG, Fang S, Cayabyab F, Zhu Q, Zhang T, Leblanc M, Liu S, et al. FXR regulates intestinal cancer stem cell proliferation. Cell. 2019;176(5):1098–1112.e18. doi:10.1016/j.cell.2019.01.036.
   PubMed Web of Science ®Google Scholar
• Xu M, Shen Y, Cen M, Zhu Y, Cheng F, Tang L, Zheng X, Kim JJ, Dai N, Hu W, et al. Modulation of the gut microbiota-farnesoid X receptor axis improves deoxycholic acid-induced intestinal inflammation in mice. J Crohns Colitis. 2021;15(7):1197–1210. doi:10.1093/ecco-jcc/jjab003.
   PubMed Web of Science ®Google Scholar
• Sorrentino G, Perino A, Yildiz E, El Alam G, Bou Sleiman M, Gioiello A, Pellicciari R, Schoonjans K. Bile acids signal via TGR5 to activate intestinal stem cells and epithelial regeneration. Gastroenterology. 2020;159(3):956–968.e8. doi:10.1053/j.gastro.2020.05.067.
   PubMed Web of Science ®Google Scholar
• Duboc H, Rajca S, Rainteau D, Benarous D, Maubert MA, Quervain E, Thomas G, Barbu V, Humbert L, Despras G, et al. Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases. Gut. 2013;62(4):531–539. doi:10.1136/gutjnl-2012-302578.
   PubMed Web of Science ®Google Scholar
• Sinha SR, Haileselassie Y, Nguyen LP, Tropini C, Wang M, Becker LS, Sim D, Jarr K, Spear ET, Singh G, et al. Dysbiosis-induced secondary bile acid deficiency promotes intestinal inflammation. Cell Host & Microbe. 2020;27(4):659–670.e5. doi:10.1016/j.chom.2020.01.021.
   PubMed Web of Science ®Google Scholar
• Haring E, FM U, Andrieux G, Proietti M, Bulashevska A, Sauer B, Braun M, de Vega Gomez L, Esser E,R, Martin P,F, et al. Bile acids regulate intestinal antigen presentation and reduce graft-versus-host disease without impairing the graft-versus-leukemia effect. Haematologica. 2021;106(8):2131–2146. doi:10.3324/haematol.2019.242990.
   PubMed Web of Science ®Google Scholar
• Ruutu T, Eriksson B, Remes K, Juvonen E, Volin L, Remberger M, Parkkali T, Hägglund H, Ringdén O. Ursodeoxycholic acid for the prevention of hepatic complications in allogeneic stem cell transplantation. Blood. 2002;100(6):1977–1983. doi:10.1182/blood-2001-12-0159.
   PubMed Web of Science ®Google Scholar
• Ruutu T, Juvonen E, Remberger M, Remes K, Volin L, Mattsson J, Nihtinen A, Hägglund H, Ringdén O. 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. doi:10.1016/j.bbmt.2013.10.014.
   PubMedGoogle Scholar
• Agus A, Planchais J, Sokol H. Gut microbiota regulation of tryptophan metabolism in health and disease. Cell Host & Microbe. 2018;23(6):716–724. doi:10.1016/j.chom.2018.05.003.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Scott SA, Fu J, Chang PV. Microbial tryptophan metabolites regulate gut barrier function via the aryl hydrocarbon receptor. Proc Natl Acad Sci USA. 2020;117(32):19376–19387. doi:10.1073/pnas.2000047117.
   PubMed Web of Science ®Google Scholar
• Venkatesh M, Mukherjee S, Wang H, Li H, Sun K, Benechet AP, Qiu Z, Maher L, Redinbo M, Phillips R, et al. Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4. Immunity. 2014;41(2):296–310. doi:10.1016/j.immuni.2014.06.014.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Rooks MG, Garrett WS. Gut microbiota, metabolites and host immunity. Nat Rev Immunol. 2016;16(6):341–352. doi:10.1038/nri.2016.42.
   PubMed Web of Science ®Google Scholar
• Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, deRoos P, deRoos P, Liu H, Cross JR, Pfeffer K, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 2013;504(7480):451–455. doi:10.1038/nature12726.
   PubMed Web of Science ®Google Scholar
• Hang S, Paik D, Yao L, Kim E, Trinath J, Lu J, Ha S, Nelson BN, Kelly SP, Wu L, et al. Bile acid metabolites control TH17 and Treg cell differentiation. Nature. 2019;576(7785):143–148. doi:10.1038/s41586-019-1785-z.
   PubMed Web of Science ®Google Scholar
• Hou Q, Ye L, Liu H, Huang L, Yang Q, Turner JR, Yu Q. Lactobacillus accelerates ISCs regeneration to protect the integrity of intestinal mucosa through activation of STAT3 signaling pathway induced by LPLs secretion of IL-22. Cell Death Differ. 2018;25(9):1657–1670. doi:10.1038/s41418-018-0070-2.
   PubMed Web of Science ®Google Scholar
• Wu K, Yuan Y, Yu H, Dai X, Wang S, Sun Z, Wang F, Fei H, Lin Q, Jiang H, et al. The gut microbial metabolite trimethylamine N-oxide aggravates GVHD by inducing M1 macrophage polarization in mice. Blood. 2020;136(4):501–515. doi:10.1182/blood.2019003990.
   PubMed Web of Science ®Google Scholar
• Aoyama K, Saha A, Tolar J, Riddle MJ, Veenstra RG, Taylor PA, Blomhoff R, Panoskaltsis-Mortari A, Klebanoff CA, Socié G, et al. Inhibiting retinoic acid signaling ameliorates graft-versus-host disease by modifying T-cell differentiation and intestinal migration. Blood. 2013;122(12):2125–2134. doi:10.1182/blood-2012-11-470252.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Hulsdunker J, Ottmuller 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.
   PubMed Web of Science ®Google Scholar
• Koyama M, Mukhopadhyay P, Schuster IS, Henden AS, Hulsdunker 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):885–898.e7. doi:10.1016/j.immuni.2019.08.011.
   PubMed Web of Science ®Google Scholar
• Fu YY, 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.
   PubMed Web of Science ®Google Scholar
• Eriguchi Y, Takashima S, Oka H, Shimoji S, Nakamura K, Uryu H, Shimoda S, Iwasaki H, Shimono N, Ayabe T, et al. Graft-versus-host disease disrupts intestinal microbial ecology by inhibiting Paneth cell production of α-defensins. Blood. 2012;120(1):223–231. doi:10.1182/blood-2011-12-401166.
   PubMed Web of Science ®Google Scholar
• Levine JE, Huber E, Hammer ST, Harris AC, Greenson JK, Braun TM, Ferrara JLM, Holler E. Low Paneth cell numbers at onset of gastrointestinal graft-versus-host disease identify patients at high risk for nonrelapse mortality. Blood. 2013;122(8):1505–1509. doi:10.1182/blood-2013-02-485813.
   PubMed Web of Science ®Google Scholar
• Ara T, Hashimoto D, Hayase E, Noizat C, Kikuchi R, Hasegawa Y, Matsuda K, Ono S, Matsuno Y, Ebata K, et al. Intestinal goblet cells protect against GVHD after allogeneic stem cell transplantation via Lypd8. Sci Transl Med. 2020;12(550):12. doi:10.1126/scitranslmed.aaw0720.
   Web of Science ®Google Scholar
• Hanash AM, Dudakov JA, Hua G, O’Connor MH, Young LF, Singer NV, West M, Jenq R, Holland A, Kappel L, 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. doi:10.1016/j.immuni.2012.05.028.
   PubMed Web of Science ®Google Scholar
• Munneke JM, Bjorklund AT, Mjosberg JM, Garming-Legert K, Bernink JH, Blom B, Huisman C, van Oers MHJ, Spits H, Malmberg K-J, et al. Activated innate lymphoid cells are associated with a reduced susceptibility to graft-versus-host disease. Blood. 2014;124(5):812–821. doi:10.1182/blood-2013-11-536888.
   PubMed Web of Science ®Google Scholar
• Hazenberg MD, Haverkate NJE, van Lier YF, Spits H, Krabbendam L, Bemelman WA, Buskens CJ, Blom B, Shikhagaie MM. Human ectoenzyme-expressing ILC3: immunosuppressive innate cells that are depleted in graft-versus-host disease. Blood Adv. 2019;3(22):3650–3660. doi:10.1182/bloodadvances.2019000176.
   PubMed Web of Science ®Google Scholar
• Biton M, Haber AL, Rogel N, Burgin G, Beyaz S, Schnell A, Ashenberg O, Su C-W, Smillie C, Shekhar K, et al. T helper cell cytokines modulate intestinal stem cell renewal and differentiation. Cell. 2018;175(5):1307–1320.e22. doi:10.1016/j.cell.2018.10.008.
   PubMed Web of Science ®Google Scholar
• Sato T, Ishikawa S, Asano J, Yamamoto H, Fujii M, Sato T, Yamamoto K, Kitagaki K, Akashi T, Okamoto R, et al. Regulated IFN signalling preserves the stemness of intestinal stem cells by restricting differentiation into secretory-cell lineages. Nat Cell Biol. 2020;22(8):919–926. doi:10.1038/s41556-020-0545-5.
   PubMed Web of Science ®Google Scholar
• Takashima S, Martin ML, Jansen SA, Fu Y, Bos J, Chandra D, O’Connor MH, Mertelsmann AM, Vinci P, Kuttiyara J, et al. T cell–derived interferon-γ programs stem cell death in immune-mediated intestinal damage. Sci Immunol. 2019;4(42):4. doi:10.1126/sciimmunol.aay8556.
   Web of Science ®Google Scholar
• Eriguchi Y, Nakamura K, Yokoi Y, Sugimoto R, Takahashi S, Hashimoto D, Teshima T, Ayabe T, Selsted ME, Ouellette AJ, et al. Essential role of IFN-γ in T cell–associated intestinal inflammation. JCI Insight. 2018;3(18):3. doi:10.1172/jci.insight.121886.
   Web of Science ®Google Scholar
• Lee C, An M, Joung JG, Park WY, Chang DK, Kim YH, Hong SN. TNFα Induces LGR5+ Stem Cell Dysfunction in Patients with Crohn’s Disease. Cell Mol Gastroenterol Hepatol. 2022;13(3):789–808. doi:10.1016/j.jcmgh.2021.10.010.
   PubMed Web of Science ®Google Scholar
• Santos AJM, Lo YH, Mah AT, Kuo CJ. The intestinal stem cell niche: homeostasis and adaptations. Trends Cell Biol. 2018;28(12):1062–1078. doi:10.1016/j.tcb.2018.08.001.
   PubMed Web of Science ®Google Scholar
• Funk MC, Zhou J, Boutros M. Ageing, metabolism and the intestine. EMBO Rep. 2020;21(7):e50047. doi:10.15252/embr.202050047.
   PubMed Web of Science ®Google Scholar
• Socie 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):131. doi:10.1172/JCI149296.
   Web of Science ®Google Scholar
• Kim KA, Kakitani M, Zhao J, Oshima T, Tang T, Binnerts M, Liu Y, Boyle B, Park E, Emtage P, et al. Mitogenic influence of human R-spondin1 on the intestinal epithelium. Science. 2005;309(5738):1256–1259. doi:10.1126/science.1112521.
   PubMed Web of Science ®Google Scholar
• Takashima S, Kadowaki M, Aoyama K, Koyama M, Oshima T, Tomizuka K, Akashi K, Teshima T. The Wnt agonist R-spondin1 regulates systemic graft-versus-host disease by protecting intestinal stem cells. J Exp Med. 2011;208(2):285–294. doi:10.1084/jem.20101559.
   PubMed Web of Science ®Google Scholar
• Hayase E, Hashimoto D, Nakamura K, Noizat C, Ogasawara R, Takahashi S, Ohigashi H, Yokoi Y, Sugimoto R, Matsuoka S, et al. R-Spondin1 expands Paneth cells and prevents dysbiosis induced by graft-versus-host disease. J Exp Med. 2017;214(12):3507–3518. doi:10.1084/jem.20170418.
   PubMed Web of Science ®Google Scholar
• Zhao D, Kim YH, Jeong S, Greenson JK, Chaudhry MS, Hoepting M, Anderson ER, van den Brink MRM, Peled JU, Gomes ALC, et al. Survival signal REG3α prevents crypt apoptosis to control acute gastrointestinal graft-versus-host disease. J Clin Invest. 2018;128(11):4970–4979. doi:10.1172/JCI99261.
   PubMed Web of Science ®Google Scholar
• Lindemans CA, Calafiore M, Mertelsmann AM, O’Connor MH, Dudakov JA, Jenq RR, Velardi E, Young LF, Smith OM, Lawrence G, et al. Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration. Nature. 2015;528(7583):560–564. doi:10.1038/nature16460.
   PubMed Web of Science ®Google Scholar
• 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. 2022;141(12):1389–1401. doi:10.1182/blood.2021015111.
   Web of Science ®Google Scholar
• Koyama M, Samson L, Ensbey KS, Takahashi S, Clouston AD, Martin PJ, Hill GR. Lithium attenuates graft-versus-host disease via effects on the intestinal stem cell niche. Blood. 2023;141(3):315–319. doi:10.1182/blood.2022015808.
   PubMed Web of Science ®Google Scholar
• Norona J, Apostolova P, Schmidt D, Ihlemann R, Reischmann N, Taylor G, Köhler N, de Heer J, Heeg S, Andrieux G, et al. Glucagon-like peptide 2 for intestinal stem cell and Paneth cell repair during graft-versus-host disease in mice and humans. Blood. 2020;136(12):1442–1455. doi:10.1182/blood.2020005957.
   PubMed Web of Science ®Google Scholar
• Fischer JC, Bscheider M, Eisenkolb G, Lin CC, Wintges A, Otten V, Lindemans CA, Heidegger S, Rudelius M, Monette S, et al. RIG-I/MAVS and STING signaling promote gut integrity during irradiation- and immune-mediated tissue injury. Sci Transl Med. 2017;9(386). doi:10.1126/scitranslmed.aag2513.
   Web of Science ®Google Scholar
• Henden AS, Koyama M, Robb RJ, Forero A, Kuns RD, Chang K, Ensbey KS, Varelias A, Kazakoff SH, Waddell N, et al. IFN-λ therapy prevents severe gastrointestinal graft-versus-host disease. Blood. 2021;138(8):722–737. doi:10.1182/blood.2020006375.
   PubMed Web of Science ®Google Scholar
• Yoshifuji K, Inamoto K, Kiridoshi Y, Takeshita K, Sasajima S, Shiraishi Y, Yamashita Y, Nisaka Y, Ogura Y, Takeuchi R, et al. Prebiotics protect against acute graft-versus-host disease and preserve the gut microbiota in stem cell transplantation. Blood Adv. 2020;4(19):4607–4617. doi:10.1182/bloodadvances.2020002604.
   PubMed Web of Science ®Google Scholar
• Andermann TM, Fouladi F, Tamburini FB, Sahaf B, Tkachenko E, Greene C, Buckley MT, Brooks EF, Hedlin H, Arai S, 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):.e932.1–.e932.11. doi:10.1016/j.jtct.2021.07.009.
   Google Scholar
• Gerbitz A, Schultz M, Wilke A, Linde HJ, Scholmerich J, Andreesen R, Holler E. Probiotic effects on experimental graft-versus-host disease: let them eat yogurt. Blood. 2004;103(11):4365–4367. doi:10.1182/blood-2003-11-3769.
   PubMed Web of Science ®Google Scholar
• Sofi MH, Wu Y, Ticer T, Schutt S, Bastian D, Choi HJ, Tian L, Mealer C, Liu C, Westwater C, et al. A single strain of Bacteroides fragilis protects gut integrity and reduces GVHD. JCI Insight. 2021;6(3):6. doi:10.1172/jci.insight.136841.
   Web of Science ®Google Scholar
• Gorshein E, Wei C, Ambrosy S, Budney S, Vivas J, Shenkerman A, Manago J, McGrath MK, Tyno A, Lin Y, 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):31. doi:10.1111/ctr.12947.
   Web of Science ®Google Scholar
• Ladas EJ, Bhatia M, Chen L, Sandler E, Petrovic A, Berman DM, Hamblin F, Gates M, Hawks R, Sung 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. doi:10.1038/bmt.2015.275.
   PubMed Web of Science ®Google Scholar
• Qi X, Li X, Zhao Y, Wu X, Chen F, Ma X. Treating Steroid Refractory Intestinal Acute Graft-vs.-Host Disease with Fecal Microbiota Transplantation: a Pilot Study. Front Immunol. 2018;9:2195. doi:10.3389/fimmu.2018.02195.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• van Lier YF, Davids M, Haverkate NJE, de Groot PF, Donker ML, Meijer E, van Lier YF, de Groot PF, Heubel-Moenen FCJI, Nur E, et al. Donor fecal microbiota transplantation ameliorates intestinal graft-versus-host disease in allogeneic hematopoietic cell transplant recipients. Sci Transl Med. 2020;12(556):12. doi:10.1126/scitranslmed.aaz8926.
   Web of Science ®Google Scholar
• Zhao Y, Li X, Zhou Y, Gao J, Jiao Y, Zhu B. 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.
   PubMed Web of Science ®Google Scholar
• 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.
   Web of Science ®Google Scholar
• Bilinski J, Lis K, Tomaszewska A, Grzesiowski P, Dzieciatkowski T, Tyszka M, Karakulska‐Prystupiuk E, Boguradzki P, Tormanowska M, Halaburda K, et al. Fecal microbiota transplantation in patients with acute and chronic graft-versus-host disease—spectrum of responses and safety profile. Results from a prospective, multicenter study. Am J Hematol. 2021;96(3):E88–E91. doi:10.1002/ajh.26077.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Vetizou M, Pitt JM, Daillere R, Lepage P, Waldschmitt N, Flament C, Rusakiewicz S, Routy B, Roberti MP, Duong CPM, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015;350(6264):1079–1084. doi:10.1126/science.aad1329.
   PubMed Web of Science ®Google Scholar
• Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, Benyamin FW, Man Lei Y, Jabri B, Alegre M-L, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy. Science. 2015;350(6264):1084–1089. doi:10.1126/science.aac4255.
   PubMed Web of Science ®Google Scholar
• Spencer CN, McQuade JL, Gopalakrishnan V, McCulloch JA, Vetizou M, Cogdill AP, Khan MAW, Zhang X, White MG, Peterson CB, et al. Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response. Science. 2021;374(6575):1632–1640. doi:10.1126/science.aaz7015.
   PubMed Web of Science ®Google Scholar
• Hu Y, Li J, Ni F, Yang Z, Gui X, Bao Z, Zhao H, Wei G, Wang Y, Zhang M, et al. CAR-T cell therapy-related cytokine release syndrome and therapeutic response is modulated by the gut microbiome in hematologic malignancies. Nat Commun. 2022;13(1):5313. doi:10.1038/s41467-022-32960-3.
   PubMed Web of Science ®Google Scholar
• Stein-Thoeringer CK, Saini NY, Zamir E, Blumenberg V, Schubert ML, 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar