Strategic Research Area OUH

The strategic research area “Personalized microbiota therapy in clinical medicine” establishes a multidisciplinary team at Oslo University Hospital, which will 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.

Projects

Genomics and Metagenomic Research Group

Project Leader: Johannes Hov
Microbiota Research
Complete microbiota profiling pipeline (lab and bioinformatics).

Department of Gastroenterology

Project Leader: Asle W. Medhus
Endoscopy and FMT experience (clinical C. difficile treatment)
IBD-studies, probiotic interventions IBD research group (Marte Lie Høivik).

Section of Gastroenterology

Project Leaders: Knut Lundin and Kjetil Garborg
Endoscopy and practical FMT expertise
Microbiota profiling in non-responsive celiac disease and FODMAP vs gluten sensitivity

Clinical Effectiveness Research

Project Leaders: Michael Bretthauer and Kjetil Garborg
Experience with clinical trials including FMT studies
Trials of FMT as primary C. difficile treatment

Clinical Microbiology and Microbiota Medicine

Project Leader: Marius Trøseid
Clinical mircrobiota reaserch
Leader of Regional network in Microbiota Science (ReMicS)

Chronic Infections Research Group

Project Leaders: Dag Henrik Reikvam and Anne Ma Dyrhol Riise
Large-volume of clinical C. difficile treatments
Studies focusing on microbial modulation of chronic infection e.g. HIV, hepatitis B and tuberculosis
Infectious risk assessments expertise
Running a small-scale microbiology lab with expertise in preparation of donor feces for FMT

Department of Microbiology

Project Leaders: Jørgen Bjørnholt, Tone Tønjum, Karianne Gammelsrud and Fredrik Müller
Know-how and routine microbiology diagnostics in OUS on fecal samples
National reference function on C. difficile
Hosts the research network “Turning the Tide of Antimicrobial resistance” (TTA), aims include metagenomic analysis and treatment of antibiotic resistance, and establishment of biobank of specimens for fecal microbiota transplantation (autologous)
Microbiological control of germfree mice in the Gnotobiotic Lab at OUS

Oncology

Project Leader: Åslaug Helland
Immune therapy in lung cancer
Planned study including microbiota profiling in immune therapy, potential for FMT from responders

Rheumatology

Project Leader: Øyvind Molberg
FMT studies in systemic sclerosis

Cardiology

Project Leaders: Lars Gullestad and Ingebjørg Seljeflot
Extensive cardiology research experience
Ongoing clinical intervention in heart failure and planned in acute coronary syndromes