Strategic Research Area OUH

The strategic research area “Personalized microbiota therapy in clinical medicine” was active 2019-2024 and established a multidisciplinary team at Oslo University Hospital, aiming to plan, coordinate and perform human trials of microbiota therapy. Clinical medicine based on stratification or modification of gut microbial composition requires gastroenterologists, infectious disease specialists, microbiologist and specialists in the individual diseases. Recently funded trials in primary C. difficile colitis, systemic sclerosis, HIV infection and cardiovascular disease highlight the potential and the need for a joint research strategy to enable rapid clinical translation and improved patient care within many fields, including inflammatory and infectious diseases as well as immune therapy for cancer.

The human gut microbiota, the total microbial content of the gastrointestinal tract, has a major impact on human health. The research groups included in the Strategic Reseach Area Project have contributed to seminal studies performing basic characterization of the disease-associated gut microbiota in multiple chronic inflammatory diseases and immunodeficiencies, and several proof-of-concept interventions targeting the microbiota, including the first trial of fecal microbiota transplantation in primary C. difficile colitis. It is demonstrated beyond doubt that disease-associated gut microbiota alterations exist. In experimental models, multiple conditions can be treated by modulating the gut microbiota, while data on how to modify the microbiota to improve disease management in humans are still lacking. One key observation is that inter-individual differences in gut microbiota composition are substantial, meaning that 1) gut microbiota medicine must be personalized, i.e. adapted to the individual, and 2) true personalized medicine must take gut microbiota into account.

Shared expertise, common methodology and analytical strategies are important to facilitate clinical implementation. This could be defined as the basic skills of the strategic area partners (Figure). These basic skills will be applied on the clinical problems, which are the expertise and topics of the groups and departments participating in this application, creating a circle of synergy.

Pillar 1: Microbiota Therapy Trials and Methods

Pillar 2: Microbiota Profiling and Biomarkers

Pillar 3: Personalized Microbiota Interventions

One important basis of this research area are planned and ongoing clinical trials, which are the critical steps before clinical implementation. Microbiota therapy require multi-disciplinary collaboration. The important concept of fecal microbiota transplantation studies is already being tested for primary C. difficile colitis (Michael Bretthauer) and systemic sclerosis (Øyvind Molberg), highlighting the needs for e.g. a) defining the appropriate and safe donor material and b) finding the best administration methods. Antibiotics and probiotics in heart failure suggest that there is a potential for targeting the gut microbiota in acute clinical settings. Drug repurposing studies highlights the potential in pharmacomicrobiomics, while studies of microbiota as prediction tool in immune therapy (Åslaug Helland) may bring this closer to the clinic in oncology.

Expertise in microbiota research and analyses is crucial to all microbiota therapy trials. This includes basic competence in microbiota-related sampling, lab work, sequencing-based profiling and bioinformatic analysis, which are all difficult and expensive to obtain within single projects. Microbiota profiles are important as end points, as donor and recipient selection criteria for treatment and as a response biomarker.

One treatment does not fit all. The second - personalized - phase of microbiota therapy trials will be based on the results of first phase trials and microbiota profiles. Ongoing interventions with obvious potential for early personalized implementation include donor selection for C. difficile colitis, and microbiota profile-based selection of candidates for immune therapy. Complex studies can only be planned and performed by using the accumulated experience across the hospital research groups, i.e. this topic is the ultimate product of the Strategic Research Area.