Lactose drives Enterococcus expansion to promote graft-versus-host disease.
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.
Duke Scholars
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Related Subject Headings
- Transplantation, Homologous
- Sequence Analysis, RNA
- RNA, Ribosomal, 16S
- Middle Aged
- Microbiota
- Mice
- Male
- Lactose
- Intestines
- Humans
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transplantation, Homologous
- Sequence Analysis, RNA
- RNA, Ribosomal, 16S
- Middle Aged
- Microbiota
- Mice
- Male
- Lactose
- Intestines
- Humans