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


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.; da Silva, M. B.; 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.
Article Title: Lactose drives Enterococcus expansion to promote graft-versus-host disease
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. © 2019 American Association for the Advancement of Science. All rights reserved.
Keywords: adult; controlled study; major clinical study; busulfan; mortality; nonhuman; mouse; mus; disease association; animal experiment; animal model; cohort analysis; genotype; cyclophosphamide; bacteria (microorganisms); disease severity; graft versus host reaction; allogeneic hematopoietic stem cell transplantation; enterococcus; bacterial colonization; intestine flora; gastrointestinal tract; rna 16s; disease exacerbation; sucrose; graft recipient; bacterium; depletion; rna sequence; enterococcus faecium; bacterial growth; colony forming unit; bacterial metabolism; disease prevalence; microbial community; digestive system; bacterial clearance; gnotobiotics; lactose; feces microflora; carbohydrate intake; bacterial overgrowth; disaccharide; bacterial translocation; human; priority journal; article; dysbiosis
Journal Title: Science
Volume: 366
Issue: 6469
ISSN: 0036-8075
Publisher: American Association for the Advancement of Science  
Date Published: 2019-11-29
Start Page: 1143
End Page: 1149
Language: English
DOI: 10.1126/science.aax3760
PUBMED: 31780560
PROVIDER: scopus
PMCID: PMC7003985
DOI/URL:
Notes: Article -- Source: Scopus
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