GUT-BLOOD-LIVER AXIS: CIRCULATING MICROBIOME AS NON-INVASIVE BIOMARKER FOR INFLAMMATORY BOWEL DISEASE (IBD) AND PRIMARY SCLEROSING CHOLANGITIS (PSC) [BLOOD-BIOME]

Project facts

Project promoter:
Lithuanian University of Health Sciences(LT)
Project Number:
LT-RESEARCH-0004
Status:
Completed
Final project cost:
€983,485
Donor Project Partners:
Oslo University Hospital(NO)
Other Project Partners
Latvian Biomedical Research and Study Centre(LV)
University of Tartu(EE)
Programme:

Description

Gut microbiome has been shown to play a crucial role in ulcerative colitis (UC) and is impaired in a related extraintestinal autoimmune condition - primary sclerosing cholangitis (PSC). One of the consequences that are associated with chronic inflammation of the intestinal mucosa is increased intestinal permeability, the so-called “leaky gut phenomenon”, which might provoke bacterial translocation to the blood through the gut-blood-liver axis. Recently, it has been reported that a considerable amount and highly divergent bacterial traces can be found in human blood samples; however, circulating blood microbiome and its diagnostic potential has not been previously investigated in UC and PSC. Therefore, in this project, a multidisciplinary research team composed of clinicians, molecular biologists and biostatisticians from Norway and Baltic countries will aim to determine circulating blood microbiome signatures in UC and related autoimmune liver disease - PSC. This aim will be achieved through the use of very well-defined large patient cohorts, advanced metagenomic sequencing techniques, and bioinformatical analysis. In addition, with the use of a germ-free UC mice model, mechanistic insights of bacterial transfer to the blood circulation will be evaluated. The project will generate clinically relevant data on the diagnostic and prognostic value of the specific circulating blood microbiota profiles, that could benefit to the generation of new non-invasive tools in the personalized management of UC and PSC. The study team will merge existing know-how, equipment and biobank resources across four different countries in order to enable the transfer of knowledge across different institutions and promote the training of young scientists and future collaborations.

Summary of project results

 The stated aim of the project was to determine circulating blood microbiome signatures in inflammatory bowel and related autoimmune liver diseases by implementing advanced collaborative multi-disciplinary research project between Norwegian and Baltic States research institutions. 

In order to ensure the reproducibility of research results, an assessment of type and starting volume of biological sample, sample preparation methodologies, DNA extraction methodologies from blood plasma was conducted. In the subsequent stage, the study focused on analyzing circulating blood and stool microbiomes in patients. A study investigating the translocation of microorganisms from the intestine into the bloodstream was conducted. 

The collected data will be used for disease risk assessment and monitoring and may generate new non-invasive tools in the personalized clinical decision-making process, which addresses the challenge of the call “Preventive and personalized medicine”. Partners from Norway and the Baltic countries collaborated to merge their existing expertise, equipment, and biobank resources across four different countries. This collaboration aimed to develop new non-invasive tools for the personalized management of UC and PSC. During the project''s implementation, conditions were created for the exchange of knowledge between institutions and the training of young scientists was encouraged.

Summary of bilateral results

Cooperation between partners was mainly carried out through cooperation and exchange of knowledge regarding the experiment and sequencing planning, determination of validation group, improvements of sample extraction methods, metagenome sequencing method establishment and the joint bioinformatic pipeline for low biomass sample analysis development. All partners closely cooperated in all project’s related activities and the draft of the first publication was prepared, reviewed, and submitted. Moreover, participating groups engaged in knowledge exchange.

Information on the projects funded by the EEA and Norway Grants is provided by the Programme and Fund Operators in the Beneficiary States, who are responsible for the completeness and accuracy of this information.