After stem cell transplantation, the donated immune cells sometimes attack the patients' bodies. This is known as graft versus host disease or GvHD. Researchers at 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 gut. In the future, it may be possible to deliberately bring about this protective composition of the microbiome.
Stem cell transplantation can save the lives of patients suffering from cancers such as leukemia. However, graft versus host reactions occur following around half of these procedures. In a sense, they are the reverse of the rejection response seen after organ donations, in which the body attacks the donated organ. Here, the donated cells attack the patient’s body, for instance, in the digestive tract.
It has been known for some time that microbes in the gut play a role in determining whether GvHD occurs. A team working with 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 Prof. Hendrik Poeck, executive senior physician at UKR’s Clinic and Polyclinic for Internal Medicine, describe in the journal Nature Cancer how the gut microbiome must be composed to provide protection.
78 patients observed
The researchers studied stool samples from 78 patients at the two university clinics and tracked them over two years following stem cell transplantation. They used the results to develop a risk index indicating the probability of a rejection reaction. “Instead of counting bacteria, we measured the quantities of certain metabolites produced by the microbes,” says Erik Thiele Orberg.
These immuno-modulatory microbial metabolites (IMMs) influence the immune system and the body’s regenerative capacity. “It is remarkable that a positive prognosis does not depend only on IMMs from bacteria,” says Dr. Elisabeth Meedt, a physician at UKR and co-first author of the article. “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.”
Better prognosis with low microbiome scores
“Patients with a low IMM risk index had a higher chance of survival, showed fewer graft vs. host reactions, and experienced fewer relapses,” says Hendrik Poeck. The metabolites are formed mainly by bacteria from the families Lachnospiraceae and Oscillospiraceae in combination with the bacteriophages.
Actively improving the probability of recovery
In the next step, the researchers at TUM and UKR want to predict and actively improve patients' chances at a cure. “By precisely controlling the composition of fecal microbiota transplants, the gut could be colonized with specific consortia of bacteria and bacteriophages,” says Hendrik Poeck. “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,” Initial experiments with mice have been successful. As a result, the procedure could now be tested in clinical trials with human patients.
Publication:
E. Thiele Orberg, E. Meedt, A. Hiergeist, J. Xue, P. Heinrich, J. Ru, S. Ghimire, O. Miltiadous, S. Lindner, M. Tiefgraber, S. Göldel, T. Eismann, A. Schwarz, S.a Göttert, S. Jarosch, K. Steiger, C. Schulz, M. Gigl, J.C. Fischer, K.-P. Janssen, M. Quante, S. Heidegger, P. Herhaus, M. Verbeek, J. Ruland, M. RM van den Brink, D. Weber, M. Edinger, D. Wolff, D.H. Busch, K. Kleigrewe, W. Herr, F. Bassermann, A. Gessner, L. Deng, E. Holler, H. Poeck. „Bacteria and Bacteriophage Consortia are Associated with Protective Intestinal Metabolites in Patients Receiving Stem Cell Transplantation.” Nature Cancer (2024). DOI: 10.1038/s43018-023-00669-x
Further information:
Additional Material for Media Outlets:
Subject matter experts:
Dr. Erik Thiele Orberg
Technical University of Munich
Klinikum rechts der Isar
Clinic and Polyclinic for Internal Medicine III
Tel. +49 89 4140 8066
e.orberg@tum.de
https://med3.mri.tum.de/de/forschung/nachwuchsgruppe-dr-erik-t-orberg
Prof. Hendrik Poeck
Universitätsklinikum Regensburg
Clinic and Polyclinic for Internal Medicine III (Hematology and Oncology)
Tel. +49 941 944-5542
https://www.ukr.de/innere-medizin-3/informationen-der-klinik-und-poliklinik/forschung/experimentelle-forschung/arbeitsgruppe-prof-dr-h-poeck
TUM Corporate Communications Center contact:
Paul Hellmich
Media Relations
Tel. +49 89 289 22731
presse@tum.de
www.tum.de
Nature Cancer
Observational study
People
Bacteria and bacteriophage consortia are associated with protective intestinal metabolites in patients receiving stem cell transplantation
3-Jan-2024
E.T.O.: honoraria (BeiGene), travel (BeiGene). M.R.M.v.d.B.: research support and stock options from Seres Therapeutics and stock options from Notch Therapeutics and Pluto Therapeutics; he has received royalties from Wolters Kluwer; he has consulted, received honorarium from or participated in advisory boards for Seres Therapeutics, Vor Biopharma, Rheos Medicines, Frazier Healthcare Partners, Nektar Therapeutics, Notch Therapeutics, Ceramedix, LyGenesis, Pluto Therapeutics, GlaxoSmithKline, Da Volterra, Thymofox, Garuda, Novartis (spouse), Synthekine (spouse), BeiGene (spouse), Kite (spouse); he has IP licensing with Seres Therapeutics and Juno Therapeutics; and he holds a fiduciary role on the foundation board of DKMS (a nonprofit organization). E.H.: scientific advisory board (MaaT Pharma, PharmaBiome (Novartis–Medac)), honoraria and research funding (Neovii, Novartis and Medac). H.P.: honoraria (Novartis, Gilead–Kite, AbbVie, Pfizer, MSD, Bristol Myers Squibb (BMS), Servier, Janssen-Cilag), travel (Janssen-Cilag, Novartis, AbbVie, Novartis, Jazz, Gilead–Kite, AMGEN), research (BMS). C.S.: honoraria (Lilly, Tillotts, Juvisé), research (Luvos). S.H. has been a consultant for BMS, Novartis, Merck, AbbVie and Roche; has received research funding from BMS and Novartis; and is an employee of and holds equity interest in Roche–Genentech. M.V.: honoraria from Novartis, Medac, AbbVie and Jazz Pharmaceuticals as well as travel grants from Medac, Gilead and Jazz Pharmaceuticals. A.S.: honoraria (BeiGene), travel (BeiGene). W.H.: honoraria (Amgen, Novartis), travel (Amgen, Janssen-Cilag). The remaining authors declare no competing interests.