Microbiome as a potential key to better treatment: Clinical study on new therapy for Crohn's disease

A special liquid diet, known as exclusive enteral nutrition, is an essential therapy for Crohn's disease. Patients consume only this formula for six to eight weeks, completely avoiding solid foods. However, the exact reasons why this is helpful were previously unclear. Researchers at the Technical University of Munich (TUM) and the LMU University Hospital Munich have now been able to decipher the mechanism behind this dietary therapy. Based on these results, they are launching a clinical study combining dietary therapy with faecal microbiome transfer to further enhance treatment outcomes.

Vitamins, minerals, proteins, carbohydrates, and fatty acids: the formula for exclusive enteral nutrition (EEN) contains all essential nutrients and is highly effective for managing Crohn's disease, often improving symptoms within a few days and without additional medical treatment. This dietary therapy has been used successfully for decades, particularly in children and adolescents, as it not only reduces inflammation but also supports growth and healing of the intestine. It is also effective in adults. However, while this approach can induce remission, symptoms often return within a year after the therapy ends.

So how can the effect of this dietary therapy be prolonged? Dirk Haller, Professor of Nutrition and Immunology at TUM and Director of the ZIEL Institute for Food and Health, and Tobias Schwerd, Head of Pediatric Gastroenterology and Hepatology at the Dr. von Hauner Children's Hospital, have developed a new therapeutic approach. The researchers demonstrated how the gut microbiome — the complex community of all microbes in the intestine — changes as a result of dietary therapy and contributes to the treatment success.

They found that the medium-chain fatty acids in the diet positively affect certain gut bacteria, which proliferate and reduce inflammation. The study reveals even more: in an artificial intestinal model, researchers treated patients' stool with the formula, thus adapting the microbiome. When this adapted microbiome was transferred to mice, no inflammation developed. However, when the microbiome was not pre-adapted by the formula, the mice developed typical inflammatory symptoms.

Joint study with the Dr. von Hauner Children's Hospital at the LMU University Hospital

The team is now conducting a clinical study to investigate whether this mechanism also works in humans — meaning whether a healthier microbiome can be established following the “microbiome reboot”. The aim is to sustain the inflammation-free state for as long as possible. To achieve this, the researchers are utilizing fecal microbiome transfer, commonly referred to as “fecal transplant”, following dietary therapy.

For the fecal mibrobiome transfer, healthy people who have been extensively screened “donate” their microbiome, which is processed into capsules. The capsules for the clinical trial are manufactured at the University Hospital of Cologne by Maria J.G.T. Vehreschild, Professor for infectious diseases, who is also involved in the clinical study. Patients take the capsules following the dietary therapy. Dirk Haller says: “Fecal microbiome transfer is already being used successfully for other intestinal diseases. We now hope it can also prove to be a new therapeutic approach for Crohn's disease.”

Tobias Schwerd says: “We are focusing on three main questions in the study: How safe is the fecal mibrobiome transfer following the dietary therapy? Is this approach feasible? And, can it stabilize disease-quiescence or at least delay the recurrence of inflammation? If we can successfully establish a healthier microbiome in the patient’s intestine for the long term, we will have made a significant step forward in therapy.”

Publication:
Häcker, D., Siebert, K., Smith, B. J. et al.: Exclusive enteral nutrition initiates individual protective microbiome changes to induce remission in pediatric Crohn’s disease,
Cell Host & Microbe (2024) doi.org/10.1016/j.chom.2024.10.001

Further information:
•    The study was conducted in the Collaborative Research Center “Microbiome Signatures" (SFB 1371).
•    Both the recently published study and the EEN-RICH study are funded by the Leona M. and Harry B. Helmsley Charitable Trust.
•    The EEN-RICH study is looking for additional participants with Crohn’s disease between the ages of 14 and 45 years. Children aged eight years and above can also participate later in the study. Further information on participation: http://www.een-rich.de/.

Subject matter experts:
Prof. Dr. Dirk Haller
Technical University of Munich
Chair of Nutrition and Immunology
Phone: +49 8161-71 2026
dirk.haller@tum.de

PD Dr. Tobias Schwerd
Dr. von Hauner Children's Hospital
Department of Pediatric Gastroenterology and Hepatology
LMU University Hospital Munich
tobias.schwerd@med.uni-muenchen.de

TUM Corporate Communications Center contact:
Anja Lapac
Media Relations Officer
Tel.: +49 8161 71-5403
presse@tum.de
www.tum.de

LMU University Hospital
Philipp Kreßirer
Tel.: +49 89 4400-58071
presse@med.uni-muenchen.de
https://www.lmu-klinikum.de/