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Science. 2019 Nov 29;366(6469):1143-1149. doi: 10.1126/science.aax3760.

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

Author information

1
Department of Immunology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
2
Weill Cornell Medical College, New York, NY, USA.
3
German Cancer Research Center (DKFZ), Heidelberg, Germany.
4
Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
5
Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
6
Department of Internal Medicine II, Technical University of Munich, Munich, Germany.
7
Gnotobiotic Facility, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
8
Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, Germany.
9
German Center for Infection Research, Partner site Bonn-Cologne, Cologne, Germany.
10
Department of Medicine, Section of Infectious Medicine and Global Health, University of Chicago, Chicago, IL, USA.
11
Infectious Disease Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
12
Laboratory of Comparative Pathology, Memorial Sloan Kettering Cancer Center, The Rockefeller University, Weill Cornell Medicine, New York, NY, USA.
13
Diagnostic Molecular Pathology Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
14
Donald B. and Catherine C. Marron Cancer Metabolism Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
15
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
16
Internal Medicine III, University Clinic Regensburg, Regensburg, Germany.
17
Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
18
Department of Hematology, Hokkaido University, Faculty of Medicine, Sapporo, Japan.
19
Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
20
Division of Infectious Diseases, Department of Medicine, Duke University, Durham, NC, USA.
21
Office of Clinical Research, Duke University School of Medicine, Durham, NC, USA.
22
Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital, Sapporo, Japan.
23
Department of Internal Medicine, Infectious Diseases, Goethe University Frankfurt, University Hospital Frankfurt, Frankfurt am Main, Germany.
24
Department of Immunology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA. peledj@mskcc.org vandenbm@mskcc.org.
#
Contributed equally

Abstract

Disruption of intestinal microbial communities appears to underlie many human illnesses, but the mechanisms that promote this dysbiosis and its adverse consequences are poorly understood. In patients who received allogeneic hematopoietic cell transplantation (allo-HCT), we describe a high incidence of enterococcal expansion, which was associated with graft-versus-host disease (GVHD) and mortality. We found that Enterococcus also expands in the mouse gastrointestinal tract after allo-HCT and exacerbates disease severity in gnotobiotic models. Enterococcus growth is dependent on the disaccharide lactose, and dietary lactose depletion attenuates Enterococcus outgrowth and reduces the severity of GVHD in mice. Allo-HCT patients carrying lactose-nonabsorber genotypes showed compromised clearance of postantibiotic Enterococcus domination. We report lactose as a common nutrient that drives expansion of a commensal bacterium that exacerbates an intestinal and systemic inflammatory disease.

Comment in

PMID:
31780560
PMCID:
PMC7003985
[Available on 2020-05-29]
DOI:
10.1126/science.aax3760
[Indexed for MEDLINE]

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