https://www.nature.com/articles/s41586-024-07667-8
A research team from Osaka Municipal University and the University of Tokyo has discovered an intestinal bacterium involved in the development of graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation, a highly toxic strain of Enterococcus faecalis, a common resident bacterium.Patients with an increased level of this strain had a higher incidence of GVHD.
The research team examined the intestinal bacteria of 46 allogeneic hematopoietic stem cell transplant patients hospitalized at Osaka Municipal University Hospital, and found an increase in Enterococcus genus bacteria in 30 of the cases. When the Enterococcus bacteria were isolated, they found that some patients had highly virulent strains of E. faecalis that produced the enzyme cytolysin which has a cytolytic effect and damages the patient’s cells. Patients with such highly virulent E. faecalis had a significantly higher incidence of GVHD than other groups, and highly virulent E. faecalis was found in 7 out of 10 patients who developed GVHD. As this strain was antibiotic-resistant, the research team could isolate a bacteriophage encoding the lytic enzyme endolysin which had a lytic effect on E. faecalis.
Administering phage-derived endolysin to mice in which highly virulent E. faecalis had taken hold and developed GVHD suppressed the worsening of GVHD and significantly increased the survival rate. In addition, when human intestinal bacteria, including highly virulent E. faecalis, were transplanted into germ-free mice to induce GVHD, and endolysin was administered to the mice, the survival rate increased.
Endolysin is resistant to gastric acid and can be administered orally.