A short-chain fatty acid made by bacteria in the gut could play an important role in graft-versus-host disease (GVHD) after allogeneic bone marrow transplant in mice. In human patients who receive bone marrow transplants, GVHD can cause severe gut damage from donor cells attacking host cells.1
This study, published in Nature Immunology, first examined chemicals made by gut bacteria after the mice received allogeneic bone marrow transplants. Results showed a reduction in the bacterial chemical butyrate in the cells lining the intestine. This butyrate reduction resulted in decreased histone acetylation.
Administering additional butyrate restored histone acetylation. It also improved junction integrity in the spaces between intestine cells, decreased intestinal cell death, and improved GVHD.
Next, researchers administered 17 strains of high butyrate-producing Clostridia, a type of bacteria, to change the butyrate production of bacteria in the guts of these mice. This also resulted in decreased GVHD. These results suggest that decreased butyrate levels could increase GVHD, while restoring butyrate levels could ameliorate the adverse effect.
“Our findings suggest we can prevent graft-versus-host disease by bolstering the amount of the microbiome-derived metabolite butyrate,” explained study lead author Pavan Reddy, MD, the Moshe Talpaz Professor of Translational Pathology and interim division chief of hematology/oncology at the University of Michigan, Ann Arbor.
“If the GI gut lining can remain healthy and strong, it can resist the attack by the donor immune system and hopefully prevent graft vs. host disease.”
Bone marrow transplants can be important components for treating some types of leukemia and lymphoma.
“This is a whole new approach. The idea is to make the host cells stronger, to be able to withstand the assault of the donor immune cells while reducing the risk of infection or leukemia relapse,” said Reddy.
1. Mathewson ND, Jenq R, Mathew AV, et al. Gut microbiome-derived metabolites modulate intestinal epithelial cell damage and mitigate graft-versus-host disease [published online ahead of print March 21, 2016]. Nat Immunol. doi:10.1038/ni.3400.