Small country with a great potential for microbiome studies

Estonian Microbiome Project, using electronic health data from 2500+ donors finds long-term antibiotic usage, independent from recent administration, has an impact on the microbiome, partly explaining the shared associations between diseases.

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The microbiome can have a major impact on public health, including identification of the microbiome–drug interactions that are responsible for the adverse drug reactions and subject-specific treatment effectiveness, management of chronic diseases, and maintenance of one’s health. Currently, there are only a few extensive population-based metagenomic cohorts available for studying the role of the microbiome and its effects on the health and progression of diseases. 

We established the Estonian Microbiome project cohort (EstMB) as part of the Estonian Biobank (EstBB). EstBB is one of the leading volunteer-based biobanks in Europe, covering almost 20% of the country’s adult population (>200,000 participants ≥18 years old). As a major strength for scientific research, comprehensive phenotype data are available from the nationwide electronic health records (EHRs), enabling monitoring of the health status across a lifespan. The EHRs are recorded by medical specialists, thus providing reliable information for disease diagnosis and prescribed medications in order to study for both prevalent and incident diseases and drug reactions. 

The timeline for Estonian Biobank (EstBB) and Estonian Microbiome project (EstMB)

In the study first introducing our project and cohort characteristics, we analyzed the gut microbiome composition in more than 2,500 adults from the EstBB. The project was established in order to study the role of the microbiome in health and disease as well as to evaluate its potential as a means to advance and implement personalized medicine, an ambitious plan for the Estonian healthcare system. EstMB includes stool, oral, and plasma samples and is supplemented with multi-omic measurements, questionnaires covering participants’ dietary preferences, lifestyle choices, and regular linkages to national electronic health records (EHRs). These possibilities allow us to study diseases and medications used in great detail, for example enabling the identification of disease subtypes, disease trajectories, and polypharmacy, which in turn can lead to novel hypotheses. 

Access to EHRs also provided us with a unique opportunity to study the effect of long-term medication usage on the fecal microbiome. In the article, we demonstrated that the long-term use of antibiotics has a remarkable effect on microbiome diversity and might partly explain shared dysbiosis between diseases. We observed significant changes in the composition of the microbiome after the participants had taken only 3–4 courses of antibiotics over the last 10 years. The fact that a shift in the microbial composition is evident with only a few courses of treatment is intriguing, as half of the participants take even more than four courses and Estonians are among the lowest consumers of antibiotics in Europe, suggesting an even stronger effect in other populations. A similar observation, although not so distinct, was also visible with antidepressant usage. After correcting for the number of antibiotic treatments taken over the last 10 years, we identified a clear decline in the number of previously detected microbiome-disease associations, underlining the value of longitudinal health data records in interpreting the results and identifying disease-specific signals. 

Although Estonian biobank has a big support system for conducting high-quality international scientific research, the core team of the Estonian microbiome project is small which means all team members are personally very invested in the success of the project. The paper was finalized in the middle of the North Estonian forest during a writing retreat where the group intensively worked days and nights to finalize the paper. This experience has strengthened our team and we are all thrilled to see what other goals we can achieve together. 

Our core team (Elin Org and Oliver Aasmets in the front and Kreete Lüll and Kertu Liis Krigul in the back)

Kertu Liis Krigul

PhD student, University of Tartu, Institute of Genomics