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.

Distinct steps in the adsorption of pulmonary surfactant to an air-liquid interface.

To investigate the mechanisms by which vesicles of pulmonary surfactant adsorb to an air-liquid interface, we measured the effect of different phospholipids and of their concentration both in the subphase and at the interface on this process. Adsorbing vesicles contained the hydrophobic surfactant proteins mixed with the following four sets of surfactant phospholipids that varied the content of anionic headgroups and mixed acyl chains independently: the complete set of purified phospholipids (PPL) from calf surfactant; modified PPL (mPPL) from which the anionic phospholipids were removed; a mixture of dipalmitoyl phosphatidylcholine (DPPC) and dipalmitoyl phosphatidylglycerol (DPPG) (9:1, mol:mol); and DPPC alone. The initial reduction in surface tension depended strongly on the anionic phospholipids and the subphase concentration. The acyl groups had no effect. Adsorption beyond the initial stage depended more on the mixed acyl groups, became increasingly independent of subphase concentration, and was determined instead by the interfacial concentration of the surface film. The different constituents produced the same effects in vesicles adsorbing to a clean interface or in a preexisting film to which vesicles of SP:DPPC adsorbed. Adsorption for vesicles of SP:PPL adsorbing to DPPC or of SP:DPPC to PPL above a certain threshold surface concentration followed exactly the same isotherm. Our results fit best with a two-step model for adsorption. The anionic phospholipids first promote the initial juxtaposition of vesicles to the interface. Compounds with mixed acyl constituents at the point of contact between vesicle and interface then facilitate fusion with the surface.