New project investigates gut microbiome for personalized bowel disease therapies

The gut microbiome plays an important role in inflammatory bowel disease. In the research project MikrobiomProCheck, researchers are investigating how microbiome data can in future be used for diagnostics, disease monitoring and personalized therapies. Bielefeld University is contributing clinical, bioinformatic and data-driven expertise to this collaborative project spanning North Rhine-Westphalia.

Which microorganisms live in a person's gut? How do they affect the body? And how are they connected to the onset and progression of inflammatory bowel disease (IBD), such as Crohn's disease and ulcerative colitis? The gut microbiome could hold important clues as to how IBD develops and progresses - and which treatment is best suited to individual patients.

The significance of microorganisms for health and disease is also highlighted by World Microbiome Day on 27 June. The collaborative project MikrobiomProCheck, in which researchers from Bielefeld University and University Hospital OWL are also involved, is investigating how this knowledge can be put to medical use. The project is being funded with around 3.4 million Euros by the North Rhine-Westphalian state government and the European Union.

Identifying correlations and patterns

The aim is to make microbiome data usable for research and therapy. Professor Dr Robert Heyer coordinates the collaborative project as head of the Multidimensional Omics Data Analysis research group at the Leibniz Institute for Analytical Sciences - ISAS - e. V. in Dortmund. The professor of bioinformatics and group leader at the Center for Biotechnology (CeBiTec) at Bielefeld University describes the microbiome as a data space in which a great deal of information comes together.

The researchers are searching for patterns: which microorganisms occur in the gut? What functions do they perform? And how does this information relate to disease, treatment success and individual differences between patients? "The correlations are so complex that they can only be systematically analysed using data-driven and AI-based methods," says Heyer. In the long term, such analyses could help to monitor the course of the disease in a gentler way. In some cases, a faecal sample alone might in future be sufficient, rather than having to repeatedly perform colonoscopies. At the same time, they are intended to indicate which medications might be particularly suitable for which patients.

Clinical data, molecular analyses and bioinformatic evaluation interlock

A fecal sample alone does not yet provide a basis for medical decision-making. Only when clinical data, molecular analyses and bioinformatic evaluation come together can patterns be identified that may be relevant for diagnosis, therapy and disease monitoring. In the clinical study, University Hospital OWL and University Hospital Essen are working closely together.

At the University Clinic for Paediatrics and Adolescent Medicine at University Hospital OWL, Professor Dr Eckard Hamelmann and Dr Patricia Maasjosthusmann are studying young IBD patients as well as healthy comparison subjects aged between six and 17. "Looking specifically at children and adolescents can help us to better understand early changes in the gut microbiome," says Heyer. Inflammatory bowel disease often begins at a young age.

University Hospital Essen is responsible for recruiting adult patients and control subjects for the study. Faecal samples and accompanying information - on diet and lifestyle, for example - are collected from all patients at several points in time. Within the project consortium, these data are compiled and analysed to investigate which factors influence the course of the disease.

Selecting cata for AI-supported analyses

Samples become data: Dr Tobias Busche of the Omics Core Facility at CeBiTec contributes Bielefeld University's genome-analysis expertise to this process. Sequencing makes it possible to determine which microbial genetic information is present in the samples and which biological functions might be associated with it. This reveals what the gut microbiome is composed of and what tasks its constituents might perform.

The next step is to identify specific patterns within this data. Professor Dr Alexander Sczyrba of the Faculty of Technology at Bielefeld University is developing bioinformatic methods that allow these large volumes of data to be analysed systematically. This enables the researchers to identify which changes in the microbiome might be linked to disease, and which data are suitable for further AI-supported analyses. The de.NBI Cloud at CeBiTec, which provides flexible computing and storage infrastructure, is also used for this purpose.

Clinical study, genome analysis and bioinformatic evaluation are closely interlinked in MikrobiomProCheck. For Professor Dr Volker Wendisch, spokesperson for the Focus Area "Microbiology in a Data-Driven World - Microbiomes and Sustainable Bioproduction" (MDDW) and Scientific Director of CeBiTec at Bielefeld University, the project exemplifies the focus area's approach: "The project is interdisciplinary, data-driven, and aims to translate microbiological insights into concrete applications." This, he says, is also what MDDW is about: bringing together microbiology, large volumes of data, bioinformatic methods and application-oriented research questions.

Professor Dr Robert Heyer: "What is special about MikrobiomProCheck is the breadth of its approach: we do not look at the gut microbiome in isolation, but combine clinical data, molecular analyses and bioinformatics. This allows us to investigate correlations that would scarcely be visible using any single method alone."

The project

MikrobiomProCheck is a broadly based, interdisciplinary research project spanning North Rhine-Westphalia: the Evangelische Klinikum Bethel - University Hospital OWL of Bielefeld University (Professor Dr Eckard Hamelmann, Dr Patricia Maasjosthusmann) and University Hospital Essen (Professor Dr Claudia Veltkamp) are responsible, for example, for the study involving ten to 20 young and 100 adult IBD patients, as well as an equal number of healthy participants.

Biofidus AG, a spin-off of Bielefeld University, and ISAS (Professor Dr Albert Sickmann) carry out the molecular analyses of the faecal samples. The analysis of the interactions between the microbiome and the immune system is conducted at University Hospital Essen (Professor Dr Astrid Westendorf, Dr Alexandra Mekes-Adamczyk). Lead Discovery Center GmbH is developing a screening method to investigate the interactions between therapeutic agents and the gut microbiome.

ISAS (Professor Dr Robert Heyer), together with the University of Bonn (Professor Dr Martin Hofmann-Apitius, Professor Dr Marie-Christine Simon, Dr Alpha Tom Kodamullil) and Bielefeld University (Professor Dr Alexander Sczyrba, Dr Tobias Busche), is jointly responsible for the AI-based microbiome analyses and for establishing the digital infrastructure.

Source:

Bielefeld University