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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Stein-Thoeringer, CK; Nichols, KB; Lazrak, A; Docampo, MD; Slingerland, AE; Slingerland, JB; Clurman, AG; Armijo, G; Gomes, ALC; Shono, Y; Staffas, A; Burgos da Silva, M; Devlin, SM; Markey, KA; Bajic, D; Pinedo, R; Tsakmaklis, A; Littmann, ER; Pastore, A; Taur, Y; Monette, S; Arcila, ME; Pickard, AJ; Maloy, M; Wright, RJ; Amoretti, LA; Fontana, E; Pham, D; Jamal, MA; Weber, D; Sung, AD; Hashimoto, D; Scheid, C; Xavier, JB; Messina, JA; Romero, K; Lew, M; Bush, A; Bohannon, L; Hayasaka, K; Hasegawa, Y; Vehreschild, MJGT; Cross, JR; Ponce, DM; Perales, MA; Giralt, SA; Jenq, RR; Teshima, T; Holler, E; Chao, NJ; Pamer, EG; Peled, JU; van den Brink, MRM

Published Date

  • November 29, 2019

Published In

Volume / Issue

  • 366 / 6469

Start / End Page

  • 1143 - 1149

PubMed ID

  • 31780560

Pubmed Central ID

  • PMC7003985

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.aax3760

Language

  • eng

Conference Location

  • United States