Precision microbiome profiling in diagnosis and disease prediction in inflammatory bowel disease

This industrial-Ph.D. is a joint research collaboration between the University of Oslo, Oslo University Hospital and Bio-Me, for studying the gut microbiome in the context of inflammatory bowel disease (IBD). IBD is a term used to describe mainly two conditions, ulcerative colitis, and Crohn?s disease, which involve a chronic inflammation of the intestinal tract. About 2.5-3 million Europeans are affected by IBD, and the number diagnosed each year is continuously increasing. The health care services must prepare for an increasing incidence. The disease course of IBD is unpredictable and differs greatly between patients. Some experience indolent disease and rare relapses, while others develop severe intestinal inflammation and might need long-term medication and/or repeated surgery. To provide the best patient care, the optimal treatment should be tailored by the predicted disease course. However, clinicians are missing the tools needed for such disease stratification. Mounting evidence is pointing at the microbiome as a key player in IBD disease. The gut microbiome is home to trillions of microorganisms, mostly bacteria, and together they exhibit functions that are crucial for our health. Under some circumstances, such as with IBD, this symbiotic relationship is broken. Bio-Me has developed Precision Microbiome Profiling (PMP), a new platform for analyzing the gut microbiome with high resolution and a short turnaround time, which makes it perfectly suited for clinical practice. IBSEN III is an ongoing, population-based observational longitudinal cohort-study, designed to answer essential questions with regards to incidence, treatment, and follow-up of patients with IBD in Norway. 2160 treatment naïve IBD patients and symptomatic controls were included throughout 2017-2019. We will analyze samples from participants in the IBSEN III study with the aim of identifying a microbial signature with diagnostic and prognostic capacity for better treatment of IBD patients.

In this project, we will combine the cutting-edge technology of Precision Microbiome Profiling (PMP) with comprehensive clinical data from a large population-based prospective IBD cohort (the IBSEN III study) to develop PMP-based microbiome profiles with diagnostic and prognostic capacity for IBD to improve patient stratification and hence patient care. The objectives will be achieved through the main work packages with the main activities: WP1: Comparison of analysis methods to analyze and evaluate our PMP technology. Shotgun metagenomic and 16S sequenced gut microbiome profiles from 84 fecal samples from IBD patients will be compared to PMP results, to understand PMP™’s position within microbiome profiling methods. The samples are already collected, handled, and sequenced, but not yet analysed by PMP. WP2: Development of PMP-IBD assays. The candidate will conduct a literature review to identify bacteria species holding a taxonomic or functional association to IBD, both diagnosis and disease progression, and use Bio-Me’s in-house software for in silico design of PMP assays for the identified species. The assays will be printed on an OpenArray panel, and the candidate will test the printed assays in vitro. These assays will be combined in an IBD-PMP panel. WP3: Analysis of IBSEN III samples on PMP. IBSEN II holds 1780 newly diagnosed and treatment naïve IBD patients and 260 symptomatic controls, and fecal samples are collected from approximately 70% of the subjects and these will be analyzed on the IBD tailored PMP-panel developed in WP2. WP4: Link microbiome to IBD diagnosis. As we are aiming to identify PMP-based microbiome profiles with diagnostic capacity for IBD in a Norwegian population the microbiome data from WP3 will be linked to diagnosis. WP5: Link microbiome to disease progression. Aiming to identify PMP-based microbiome profiles with prognostic capacity for IBD in a Norwegian population we will link results from WP3 to one-year disease outcome.