Research group of microbiome

In 2017, we started collecting oral and stool microbiome samples from Estonian population in order to investigate the role of the host microbiome in health and disease. The study participants were selected from Estonian Biobank. For each study participant, we have lifestyle and health related data from self-reported questionnaires, as well as health data from national health registers. Rich data resources allow us to characterize the Estonian population microbiome profile and identify microbiome-associated factors.

Sample types: 2509 Oral, stool, plasma samples

Data for analysis: Stool metagenomics data (avg. 4-5Gb/person), host genotypes, linking to electronic health records (EHRs), self-reported questionnaires (health, environmental/life-style data) 

Contact: Elin Org, elin.org@ut.ee 

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In collaboration with University of Tartu Hospital we investigate the role of gut microbiome in development of colorectal cancer (CRC). We currently collect oral, fecal, plasma and biopsy samples from individuals who participate in the national CRC screening program in Estonia. The overall aim of the project is to find new microbiome-based biomarkers that would allow earlier and more accurate detection of colon cancer and contribute to the development of new diagnostic methods for CRC.

Collaborators: The Internal Medicine Clinic of Tartu University Hospital, The Gastroenterology department; The Haematology and Oncology Clinic of Tartu University Hospital  

Sample types: Oral, different stool samples (FIT tubes, stabilization buffer, Fresh-frozen), blood, biopsy samples (polyp tissue, healthy epithelial tissue, tumor tissue)

Data for analysis: 16S rRNA gene (V3-V4) sequencing, DNA, RNA, immune cells, histology data, questionnaire

Related publications: 

• A desirable aim would be the possibility to analyze microbiome from the fecal samples collected during CRC screening programs into FIT tubes for fecal occult blood testing. Our study shows that FIT tubes can be used for profiling the gut microbiota in colorectal cancer screening programs as the community is similar to fresh frozen samples and stable at least for 7 days. Sample material from FIT tubes could be used in addition to fecal immunochemical tests for future investigations into the role of gut microbiota in colorectal cancer screening programs circumventing the need to collect additional samples and possibly improving the sensitivity of FIT.
• Kertu Liis Krigul, Oliver Aasmets, Kreete Lüll, Tõnis Org, Elin Org Using fecal immunochemical tubes for the analysis of the gut microbiome has the potential to improve colorectal cancer screening  

Contact: Kertu Liis Krigul (kertu.krigul@ut.ee)

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The effect of the microbiome to the etiology and treatment of inflammatory bowel diseases

Gut microbiome alterations have been clearly linked with inflammatory human diseases. Multiple reports have shown that patients with Ulcerative colitis have impaired intestinal barrier (so called “leaky gut”) and bacteria may translocate into circulation via gut-blood-liver axis. Moreover, recent studies have shown that blood has unique circulating microbial signatures in certain diseases. The idea of our project is to determine circulating blood, and stool microbiome signatures in Ulcerative colitis, Crohn’s disease and primary sclerosing cholangitis and evaluate diagnostic and prognostic value of these biomarkers. In addition, the effect of the microbiome on the treatment of these diseases will be evaluated. 

Collaborators: The Internal Medicine Clinic of Tartu University Hospital, The Gastroenterology department 

Sample types: Stool (multiple timepoints), blood (multiple timepoints)

Data for analysis: 16S rRNA sequencing (V3-V4)

Contact: Elin Org (elin.org@ut.ee)

The incidence of type 2 diabetes (T2D) has been increasing globally, and a growing body of evidence links type 2 diabetes with altered microbiota composition. Type 2 diabetes is preceded by a long prediabetic state characterized by changes in various metabolic parameters. In this study we tested whether the gut microbiome could have predictive potential for T2D development during the healthy and prediabetic disease stages. We used prospective data of 608 well-phenotyped Finnish men collected from the population-based Metabolic Syndrome in Men (METSIM) study to build machine learning models for predicting continuous glucose and insulin measures in a shorter (1.5 year) and longer (4 year) period. Ongoing studies use the METSIM data for comparing various machine learning methods on microbiome data and the METSIM data will be further used for building and validating microbial risk scores for various metabolic traits. 

Collaborators: prof. Markku Laakso, University of Kuopio, Finland; prof. Aldons J. Lusis, University of California, Los Angeles

Sample types: stool, plasma

Data for analysis: 16S rRNA V3-V4 region sequences, NMR metabolites, plasma measurements, 

Related publications:

• “Relationships between gut microbiota, plasma metabolites, and metabolic syndrome traits in the METSIM cohort” https://lusis.genetics.ucla.edu/sites/default/files/pubpdf/PMC5390365.p…
• “Machine Learning Reveals Time-Varying Microbial Predictors with Complex Effects on Glucose Regulation” https://journals.asm.org/doi/10.1128/mSystems.01191-20 

Contact:  Oliver Aasmets (oliver.aasmets@ut.ee)

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In collaboration with University of Tartu Clinic we set up study where we collect type 2 diabetes patients who will be treated with two new antidiabetic drugs: 1) semaglutide (human glucagon-like peptide -1 (GLP-1) receptor agonist, that increases insulin secretion) and 2) empagliflozin (inhibitor of the sodium glucose co-transporter -2 (SGLT-2), that ameliorates vascular function and thus has advantageous effects on CVD). We collect gut microbiome and blood samples before and after treatment and evaluate the changes of gut microbiome on the effect of both drugs. We are currently enrolling patients in this study.

Collaborators: Dr. Ingrid Reppo; prof. Vallo Volke from Institute of Biomedicine and Translational Medicine, Faculty of Medicine, University of Tartu

Sample types: Stool in RNA later, plasma

Data for analysis: 16S V3-V4 sequencing 

Contact: Elin Org (elin.org@ut.ee)

The aim of this project is to investigate whether the microbial community of endometrial tissue (ET) and endometrial fluid (EF) samples differ from one another in IVF patients. The second aim of the project was to search for possible associations between chronic endometritis and endometrial microbiota. As a result it was seen that the differences in microbial profiles of EF and ET samples are driven by Lactobacillus abundance. We also report that the microbiome of women with and without chronic endometritis in our sample set of IVF patients was similar.

Collaborators: Department of Obstetrics and Gynaecology, Institute of Clinical Medicine, University of Tartu, Estonia; Center of Human Reproduction “Genesis”, St. Petersburg, Russia; Department of Obstetrics and Gynecology, State Pediatric Medical University, St. Petersburg, Russia.

Sample types: endometrial tissue samples, uterine fluid samples

Data for analysis: 16S rRNA sequencing, chromatography

Contact: Kreete Lüll (kreete.lull@ut.ee)

In this study we compare the gut microbiome in late fertile age women with and without PCOS and investigate whether changes in the gut microbiome correlate with PCOS-related metabolic parameters. The study population consists of 102 women with PCOS and 201 healthy BMI- and age-matched controls belonging to the Northern Finland 1966 birth cohort. Clinical and biochemical characteristics of the participants were assessed at ages 31 and 46. Oral glucose tolerance test was performed to evaluate glucose tolerance. Stool samples were collected at the age of 46 and 16S rRNA sequencing using regions V3-V4 was performed. Collaboration continues and in the next steps the focus will be on the metabolites and gut microbiome in PCOS women.   

Aim of the project was to compare the gut microbiome in late fertile age women with and without PCOS and to investigate whether changes in the gut microbiome correlate with PCOS-related metabolic parameters.

Collaborators: prof. Terhi Piltonen, Riikka Arffman, Laure Morin-Papunen and Juha Tapanainen  University of Oulu, Finland; Signe Altmäe, University of Granada, Spain; prof Stephen Franks, Imperial College London, United Kingdom; prof Andres Salumets, Department of Obstetrics and Gynaecology, Institute of Clinical Medicine, University of Tartu, Estonia.

Sample types: stool 

Data for analysis: 16S rRNA sequencing, longitudinal data from questionnaires, metabolites data

Related publications: First article on this matter was published in the Journal of Clinical Endocrinology and Metabolism. https://doi.org/10.1210/clinem/dgaa848

Contact: Kreete Lüll (kreete.lull@ut.ee)

Funding:

• Estonian Research Council grant PUT 1371 
• EMBO Installation grant 3573
• European Regional Development Fund Project No. 15-0012 GENTRANSMED
• Estonian Center of Genomics/Roadmap II project No 16-0125