Lactose drives Enterococcus expansion to promote graft-versus-host disease
Open accessAbstract
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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Animal models indicate that commensal bacteria affect GVHD pathophysiology.
“Preclinical models have shown that commensal bacteria influence the pathophysiology of GVHD.10,17–20”
From Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation (2020) · cites this paper as [20]
Enterococcus has been linked to post-transplant graft-versus-host disease.
“Enterococcus has been associated with the development of post-HCT graft-versus-host disease5.”
From A non-antibiotic-disrupted gut microbiome is associated with clinical responses to CD19-CAR-T cell cancer immunotherapy (2023) · cites this paper as [5]
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Self-citationGut microbiota and sepsis: from pathogenesis to novel treatments
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The role of the microbiota in the management of intensive care patients
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Management of Nutritional Needs in Pediatric Oncology: A Consensus Statement
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Roles of the intestinal microbiota and microbial metabolites in acute GVHD
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Nonclassical manifestations of acute GVHD
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Lytic Bacteriophages Facilitate Antibiotic Sensitization of Enterococcus faecium
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Allogeneic hematopoietic cell transplantation, the microbiome, and graft-versus-host disease
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The Gut Microbiome in Sepsis: From Dysbiosis to Personalized Therapy
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Self-citationMicrobiota-derived metabolites: Key modulators of cancer immunotherapies
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An enterococcal phage-derived enzyme suppresses graft-versus-host disease
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Self-citationGlobal diversity of enterococci and description of 18 previously unknown species
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Targeting the gut microbiome: An emerging trend in hematopoietic stem cell transplantation
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Self-citationEnterococci facilitate polymicrobial infections
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Gut microbiota, microbiota‐derived metabolites, and graft‐versus‐host disease
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Self-citationChildren and adults should avoid consuming animal products to reduce risk for chronic disease: NO
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Self-citationCAR-T Cell Therapy and the Gut Microbiota
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Immune Suppression in Allogeneic Hematopoietic Stem Cell Transplantation
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Bacteroides ovatus alleviates dysbiotic microbiota-induced graft-versus-host disease
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Translating Microbiome Research From and To the Clinic
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The Pathophysiology and Treatment of Graft-Versus-Host Disease: Lessons Learnt From Animal Models
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Tyrosine supplement ameliorates murine aGVHD by modulation of gut microbiome and metabolome
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Emerging roles of the gut microbiota in cancer immunotherapy
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Faecal (or intestinal) microbiota transplant: a tool for repairing the gut microbiome
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Microbiome-Derived Metabolites in Allogeneic Hematopoietic Stem Cell Transplantation
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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
- Published
- 2019-11-29
- Volume
- 366
- Issue
- 6469
- Pages
- 1143-1149
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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