Faecal microbiota transplants could help to prevent graft versus host disease (GvHD) after stem cell transplantations, according to a new German study.
Researchers at the Technical University of Munich and the Universitätsklinikum Regensburg (UKR) found the risk of GvHD is significantly reduced when certain microbes are present in the gut.
The team was led by Dr Erik Thiele Orberg, who heads a research group at the Clinic and Polyclinic for Internal Medicine III of TUM’s Klinikum rechts der Isar, Ernst Holler, senior professor of Allogenic Stem Cell Transplantation at UKR, and Professor Hendrik Poeck, executive senior physician at UKR’s Clinic and Polyclinic for Internal Medicine.
Writing in the journal Nature Cancer, they say it may be possible to use faecal transplants to create a protective environment to improve long-term outlook for transplant recipients.
In their study, the team analysed stool samples from 78 patients at the two university clinics and tracked them over two years following stem cell transplantation, measuring the amount of different types of microbes but also the metabolites they produce.
They used the results to develop a risk index indicating the probability of a GvHD reaction by measuring the quantities of immuno-modulatory microbial metabolites (IMMs), which influence the immune system and the body’s regenerative capacity.
Prof Poeck added: “Patients with a low IMM risk index had a higher chance of survival, showed fewer graft vs host reactions, and experienced fewer relapses.”
Co-first author Dr Elisabeth Meedt, a physician at UKR, said: “It is remarkable that a positive prognosis does not depend only on IMMs from bacteria.
“We demonstrated that certain viruses in the gut – the bacteriophages – also play a role. This alone offers an impressive insight into the complex world of our gut microbiome.”
The metabolites are mainly formed by bacteria from the families Lachnospiraceae and Oscillospiraceae, in combination with the bacteriophages. The research team are now hoping to be able to predict and actively improve patients’ chances at a cure.
Prof Poeck said: “By precisely controlling the composition of faecal microbiota transplants, the gut could be colonised with specific consortia of bacteria and bacteriophages.
“In the coming years, we want to find out whether we can use this approach to prevent graft vs host reactions as well as relapses.”
After initial successful experiments with mice, the procedure could now be tested in clinical trials with human patients.
Thiele Orberg E, Meedt E, Hiergeist A, Xue J, Heinrich P, Ru J, Ghimire S, Miltiadous O, Lindner S, Tiefgraber M, Göldel S, Eismann T, Schwarz A, Göttert S, Jarosch S, Steiger K, Schulz C, Gigl M, Fischer JC, Janssen KP, Quante M, Heidegger S, Herhaus P, Verbeek M, Ruland J, van den Brink MRM, Weber D, Edinger M, Wolff D, Busch DH, Kleigrewe K, Herr W, Bassermann F, Gessner A, Deng L, Holler E, Poeck H. (2023) “Bacteria and Bacteriophage Consortia are Associated with Protective Intestinal Metabolites in Patients Receiving Stem Cell Transplantation.” Nature Cancer, doi: 10.1038/s43018-023-00669-x
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