Lactose drives <i>Enterococcus</i> expansion to promote graft-versus-host disease

Christoph K. Stein‐Thoeringer(Memorial Sloan Kettering Cancer Center), Katherine Nichols(Memorial Sloan Kettering Cancer Center), Amina Lazrak(Memorial Sloan Kettering Cancer Center), Melissa D. Docampo(Memorial Sloan Kettering Cancer Center), Ann E. Slingerland(Memorial Sloan Kettering Cancer Center), John Slingerland(Memorial Sloan Kettering Cancer Center), Annelie Clurman(Memorial Sloan Kettering Cancer Center), Gabriel K. Armijo(Memorial Sloan Kettering Cancer Center), Antonio L. C. Gomes(Memorial Sloan Kettering Cancer Center), Yusuke Shono(Memorial Sloan Kettering Cancer Center), Anna Staffas(Memorial Sloan Kettering Cancer Center), Marina Burgos da Silva(Memorial Sloan Kettering Cancer Center), Sean M. Devlin(Memorial Sloan Kettering Cancer Center), Kate A. Markey(Memorial Sloan Kettering Cancer Center), Danica Bajic(Technical University of Munich), R. Pinedo(Memorial Sloan Kettering Cancer Center), Anastasia Tsakmaklis(University of Cologne), Eric R. Littmann(Memorial Sloan Kettering Cancer Center), Alessandro Pastore(Memorial Sloan Kettering Cancer Center), Ying Taur(Memorial Sloan Kettering Cancer Center), Sébastien Monette(Memorial Sloan Kettering Cancer Center), Maria E. Arcila(Memorial Sloan Kettering Cancer Center), Amanda J. Pickard(Memorial Sloan Kettering Cancer Center), Molly Maloy(Memorial Sloan Kettering Cancer Center), Roberta J. Wright(Memorial Sloan Kettering Cancer Center), Luigi A. Amoretti(Memorial Sloan Kettering Cancer Center), Emily Fontana(Memorial Sloan Kettering Cancer Center), Dung Pham(The University of Texas MD Anderson Cancer Center), Mohamed A. Jamal(The University of Texas MD Anderson Cancer Center), Daniela Weber(University Hospital Regensburg), Anthony D. Sung(Duke Medical Center), Daigo Hashimoto(Hokkaido University), Christof Scheid(University of Cologne), João B. Xavier(Memorial Sloan Kettering Cancer Center), Julia A. Messina(Duke University), Kristi Romero(Duke University), M. Lew(Duke Medical Center), Amy Bush(Duke Medical Center), Lauren Bohannon(Duke Medical Center), Kasumi Hayasaka(Hokkaido University Hospital), Yuta Hasegawa(Hokkaido University), Maria J. G. T. Vehreschild(Goethe University Frankfurt), Justin R. Cross(Memorial Sloan Kettering Cancer Center), Doris M. Ponce(Memorial Sloan Kettering Cancer Center), Miguel‐Angel Perales(Memorial Sloan Kettering Cancer Center), Sergio Giralt(Memorial Sloan Kettering Cancer Center), Robert R. Jenq(The University of Texas MD Anderson Cancer Center), Takanori Teshima(Hokkaido University), Ernst Holler(University Hospital Regensburg), Nelson J. Chao(Duke Medical Center), Eric G. Pamer(Memorial Sloan Kettering Cancer Center), Jonathan U. Peled(Memorial Sloan Kettering Cancer Center), Marcel R.M. van den Brink(Memorial Sloan Kettering Cancer Center)
Science
November 28, 2019
10.1126/science.aax3760
Cited by 366Open Access
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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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