Cited by 384Hematopoietic Stem Cell TransplantationGut microbiota and healthNeutropenia and Cancer Infections

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Lactose drives Enterococcus expansion to promote graft-versus-host disease

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Stein-Thoeringer, C. K., Nichols, K. B., Lazrak, A., Docampo, M. D., Slingerland, A. E., Slingerland, J. B., Clurman, A. G., Armijo, G., Gomes, A. L. C., Shono, Y., Staffas, A., Burgos da Silva, M., Devlin, S. M., Markey, K. A., Bajic, D., Pinedo, R., Tsakmaklis, A., Littmann, E. R., Pastore, A., Taur, Y., Monette, S., Arcila, M. E., Pickard, A. J., Maloy, M., Wright, R. J., Amoretti, L. A., Fontana, E., Pham, D., Jamal, M. A., Weber, D., Sung, A. D., Hashimoto, D., Scheid, C., Xavier, J. B., Messina, J. A., Romero, K., Lew, M., Bush, A., Bohannon, L., Hayasaka, K., Hasegawa, Y., Vehreschild, M. J. G. T., Cross, J. R., Ponce, D. M., Perales, M. A., Giralt, S. A., Jenq, R. R., Teshima, T., Holler, E., Chao, N. J., Pamer, E. G., Peled, J. U., van den Brink, M. R. M.·2019·Science

DOI 10.1126/science.aax3760PMC PMC7003985

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Abstract

Lactose can fuel GVHD: Allogeneic hematopoietic cell transplantation (allo-HCT) is used to treat certain hematopoietic malignancies, but patients have a risk of developing graft-versus-host disease (GVHD). Stein-Thoeringer et al. performed a large-scale analysis of more than 1300 patients treated with allo-HCT across four clinical centers (see the Perspective by Zitvogel and Kroemer). High levels of bacteria from the Enterococcus genus were associated with greater incidence of GVHD and mortality. Lactose appears to provide a substrate for Enterococcus growth, and patients with a lactose-malabsorption genotype had a greater abundance of Enterococcus. A lactose-free diet limited Enterococcus growth, reduced the severity of GVHD, and improved survival in gnotobiotic mouse models. Science , this issue p. 1143 ; see also p. 1077

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Additional file 19 of Linking gastrointestinal microbiota and metabolome dynamics to clinical outcomes in paediatric haematopoietic stem cell transplantation
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Additional file 16 of Linking gastrointestinal microbiota and metabolome dynamics to clinical outcomes in paediatric haematopoietic stem cell transplantation
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Additional file 12 of Linking gastrointestinal microbiota and metabolome dynamics to clinical outcomes in paediatric haematopoietic stem cell transplantation
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Additional file 2 of Microbiota long-term dynamics and prediction of acute graft-versus-host disease in pediatric allogeneic stem cell transplantation
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Additional file 5 of Linking gastrointestinal microbiota and metabolome dynamics to clinical outcomes in paediatric haematopoietic stem cell transplantation
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Additional file 14 of Linking gastrointestinal microbiota and metabolome dynamics to clinical outcomes in paediatric haematopoietic stem cell transplantation
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Additional file 10 of Linking gastrointestinal microbiota and metabolome dynamics to clinical outcomes in paediatric haematopoietic stem cell transplantation
Vaitkute, G., Panić, G., Alber, D., Faizura-Yeop, I., Cloutman-Green, E., Swann, J., Veys, P. A., Standing, J. F., Klein, N. J., & Bajaj‐Elliott, M. (2022) · Figshare · doi:10.6084/m9.figshare.20056032
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Authors: Stein-Thoeringer, C. K., Nichols, K. B., Lazrak, A., Docampo, M. D., Slingerland, A. E., Slingerland, J. B., Clurman, A. G., Armijo, G., Gomes, A. L. C., Shono, Y., Staffas, A., Burgos da Silva, M., Devlin, S. M., Markey, K. A., Bajic, D., Pinedo, R., Tsakmaklis, A., Littmann, E. R., Pastore, A., Taur, Y., Monette, S., Arcila, M. E., Pickard, A. J., Maloy, M., Wright, R. J., Amoretti, L. A., Fontana, E., Pham, D., Jamal, M. A., Weber, D., Sung, A. D., Hashimoto, D., Scheid, C., Xavier, J. B., Messina, J. A., Romero, K., Lew, M., Bush, A., Bohannon, L., Hayasaka, K., Hasegawa, Y., Vehreschild, M. J. G. T., Cross, J. R., Ponce, D. M., Perales, M. A., Giralt, S. A., Jenq, R. R., Teshima, T., Holler, E., Chao, N. J., Pamer, E. G., Peled, J. U., & van den Brink, M. R. M.
Affiliations: Department of Immunology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Memorial Sloan Kettering Cancer Center (US)
Technical University of Munich (DE)
University of Cologne (DE)
The University of Texas MD Anderson Cancer Center (US)
University Hospital Regensburg (DE)
Duke Medical Center (US)
Hokkaido University (JP)
Duke University (US)
Hokkaido University Hospital (JP)
Goethe University Frankfurt (DE)
ORCID: Stein-Thoeringer, C. K.
Nichols, K. B.
Lazrak, A.
Docampo, M. D.
Slingerland, A. E.
Slingerland, J. B.
Clurman, A. G.
Armijo, G.
Gomes, A. L. C.
Shono, Y.
Staffas, A.
Burgos da Silva, M.
Devlin, S. M.
Markey, K. A.
Bajic, D.
Pinedo, R.
Tsakmaklis, A.
Littmann, E. R.
Pastore, A.
Taur, Y.
Monette, S.
Arcila, M. E.
Pickard, A. J.
Maloy, M.
Wright, R. J.
Amoretti, L. A.
Fontana, E.
Pham, D.
Jamal, M. A.
Weber, D.
Sung, A. D.
Hashimoto, D.
Scheid, C.
Xavier, J. B.
Messina, J. A.
Romero, K.
Lew, M.
Bush, A.
Bohannon, L.
Hasegawa, Y.
Vehreschild, M. J. G. T.
Cross, J. R.
Ponce, D. M.
Perales, M. A.
Giralt, S. A.
Jenq, R. R.
Teshima, T.
Holler, E.
Chao, N. J.
Pamer, E. G.
Peled, J. U.
van den Brink, M. R. M.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2019-11-29
Volume: 366
Issue: 6469
Pages: 1143-1149
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.aax3760
PMC: PMC7003985
OpenAlex: W2990824191
Cited by: 384
References: 55
Citations by year: 2026: 46 · 2025: 60 · 2024: 52 · 2023: 59 · 2022: 69 · 2021: 57 · 2020: 39 · 2019: 1
FWCI: 29.38
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
PubMed Central (acceptedVersion)
University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
Funders: National Institutes of Health (1R01HL124112-01A)
National Institute on Aging (P01-AG052359, 2P30AG028716-11)
National Heart, Lung, and Blood Institute (R01-HL125571, R01-HL123340)
National Cancer Institute (R01-CA228358, R01CA203950-01, R01 CA203950-01, P30 CA008748, P01-CA023766, R01-CA228308)
National Institute of Allergy and Infectious Diseases (U01 AI124275, R01 AI032135)
German research Foundation
Topics: Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Health Sciences › Medicine › Oncology › Neutropenia and Cancer Infections
Keywords: lactose, Enterococcus, graft-versus-host disease, allogeneic hematopoietic stem cell transplantation, lactose malabsorption, gut microbiota, lactose-free diet, bacterial growth substrates, post-transplant mortality, gnotobiotic mouse model
MeSH terms: Gastrointestinal Microbiome, Aged, Animals, Feces, Female, Graft vs Host Disease, Humans, Intestines, Lactose, Male, Middle Aged, RNA, Ribosomal, 16S, Transplantation, Homologous, Enterococcus, Sequence Analysis, RNA, Hematopoietic Stem Cell Transplantation, Mice, Microbiota, Dysbiosis

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Lactose drives Enterococcus expansion to promote graft-versus-host disease

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