Certain combinations of gut bacteria protect stem cell transplant patients from immune reactions, study finds

After a stem cell transplant, the donated immune cells sometimes attack patients’ bodies. This is called graft-versus-host disease or GvHD. Researchers from the Technical University of Munich (TUM) and the Universitätsklinikum Regensburg (UKR) have shown that GvHD is much less common when certain microbes are present in the intestine. In the future, it may be possible to deliberately create this microbiome-protective composition.

Stem cell transplantation can save the lives of patients suffering from cancers such as leukemia. However, graft-versus-host disease occurs after about half of these procedures. In a sense, they are the opposite of the rejection reaction seen after organ donation, in which the body attacks the donated organ. Here the donated cells attack the patient’s body, for example in the digestive tract.

It has been known for some time that microbes in the gut play a role in determining whether GvHD develops. A team working with Dr. Erik Thiele Orberg, who leads a research group at the Internal Medicine Clinic and Polyclinic III of the Klinikum rechts der Isar of TUM, Ernst Holler, Senior Professor of Allogeneic Stem Cell Transplantation at UKR, and Professor Hendrik Poeck, Executive Chief Physician at the UKR Internal Medicine Clinic and Polyclinic, described in the journal Natural cancer how the gut microbiome should be composed to provide protection.

The researchers studied stool samples from 78 patients from the two university clinics and followed them for two years after stem cell transplantation. They used the results to develop a risk index indicating the likelihood of a rejection response. “Instead of counting bacteria, we measured the amounts of certain metabolites produced by microbes,” says Orberg.

These immunomodulatory microbial metabolites (IMMs) influence the immune system and the body’s regenerative capacity. “It is remarkable that a positive prognosis does not depend solely on IMMs from bacteria,” says Dr. Elisabeth Meedt, a doctor at UKR and co-first author of the article. “We have demonstrated that certain viruses in the gut, bacteriophages, also play a role. This alone offers an impressive insight into the complex world of our gut microbiome.”

“Patients with a low IMM risk index had a greater chance of survival, had less graft-versus-host disease, and experienced fewer relapses,” says Poeck. Metabolites are formed mainly by bacteria from the Lachnospiraceae and Oscillospiraceae families in combination with bacteriophages.

In the next step, researchers at TUM and UKR want to actively predict and improve patients’ chances of recovery. “By precisely controlling the composition of fecal microbiota transplants, the intestine could be colonized by specific consortia of bacteria and bacteriophages,” explains Poeck. “In the coming years, we want to find out if we can use this approach to prevent graft-versus-host disease as well as relapses.”

The first experiments with mice were successful. As a result, the procedure could now be tested in clinical trials on human patients.