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LATVIAN

BIOMEDICAL

RESEARCH AND STUDY CENTRE


RESEARCH AND EDUCATION IN BIOMEDICINE FROM GENES TO HUMAN

Project Title: „Role of miRNAs in the host-gut microbiome communication during metformin treatment in the context of metabolic disorders”

Funding: European Regional Development Fund (ERDF), Measure 1.1.1.1 “Support for applied research”

Project No.: 1.1.1.1/18/A/092

Period: 1 April 2019 – 31 March 2022

Project costs: 648 648 EUR

Principle Investigator: Dr. biol. Jānis Kloviņš

Cooperation partner: SIA “GenEra”

Project summary:

Changes in core gut microbiome are associated with a wide variety of diseases, however, the mechanisms of interaction in the ability of the host to regulate these deviations are still unclear and under-investigated. Recently host miRNAs were shown to be involved in the communication between the host and its gut microbiome. There are still many caveats in the understanding of the possible mechanisms and the actual impact of observed association and further research is needed. Equally important is to understand the communication in relation to gut microbiome-related diseases such as type 2 diabetes (T2D) not only to understand the mechanisms of these phenomena in disease, but also to open opportunity for creation of completely novel therapeutic strategies.

The overall aim of the project is to investigate the contribution of the host miRNAs in metformin-mediated changes in gut microbiome composition and functions in the context of type 2 diabetes and to identify miRNAs which could be directed to potential clinical studies.

We will use notable sample resources collected in the framework of a previously performed mice experiment. In addition we will use samples from patients with different metabolic backgrounds obtained during colonoscopy procedure.

We will obtain gut metagenome and miRNA composition data by NGS and estimate the correlation between miRNA and gut microbiome profiles in high-fat diet-fed mice model and patients.

This project will result in a novel understanding of host miRNA-microbiome interaction in T2D and deliver new knowledge for development of personalized approaches in T2D treatment or improvement of the existing strategies.

Information published 01.04.2019.

Progress of the project:

1 April 2019 – 30 June 2019

In this period of the project processing of the gut microbiome samples obtained during an animal experiment has been started. We have selected microbiome samples representing gut lumen and mucosa from our sample collection. We have performed the isolation of bacterial DNA from various segments of gut and have started to prepare them for massive parallel sequencing. In addition, we have summarized the inclusion criteria for human volunteers. Methodology and protocols necessary for the analysis of human microbiome samples have been developed.

Information published 28.06.2019.

Progress of the project:

1 July 2019 – 30 September 2019

In this period quality control of microbial DNA samples and their preparation for massive parallel sequencing has continued. We have started to sequence bacterial DNA samples obtained from different intestinal segments by 16S rRNA gene sequencing method. Initial analysis of the obtained data is ongoing. We have started the selection of samples for RNA isolation and we are developing methodology and protocols necessary for further analysis of these samples. In addition, we have developed methodology and protocols necessary for the analysis of human microbiome samples.

Information published 30.09.2019.

Progress of the project:

1 October 2019 – 31 December 2019

In this period quality control of microbial DNA samples and their preparation for massive parallel sequencing has continued. Sequencing of bacterial DNA samples obtained from different intestinal segments by 16S rRNA gene sequencing method continues. Initial analysis of the obtained data is ongoing. Selection of samples for RNA isolation is in process and we have chosen methodology and prepared protocols necessary for further analysis of these samples. Collection of human gut microbiome samples has been initiated.

Information published 30.12.2019.

Progress of the project:

1 January 2020 – 31 March 2020

In this period sequencing of microbial DNA samples obtained from different intestinal segments by 16S rRNA gene sequencing method has been finished. Isolation of RNA, its quality control and sample preparation for further analysis is ongoing. Analysis of the obtained data is ongoing. Work on collection of human gut microbiome samples continues.

Information published 31.03.2020.

Progress of the project:

1 April 2020 – 30 June 2020

Analysis of sequencing data representing microbial DNA samples obtained from different intestinal segments by 16S rRNA gene sequencing method is ongoing. Isolation of nucleic acids, their quality control and sample preparation for further analysis continues, planning of optimal sequencing strategy is ongoing. Work on collection of human gut microbiome samples continues.

Information published 30.06.2020.

Progress of the project:

1 July 2020 – 30 September 2020

Analysis of sequencing data representing microbial DNA samples and compilation of results is ongoing. MiRNA sequencing has been performed, data analysis is in progress. Human gut microbiome samples have been collected. Sample processing and preparation for sequencing is ongoing. Assembling of the information on the participants involved in the study has been started.

Information published 30.09.2020.

Progress of the project:

1 October 2020 – 31 December 2020

Analysis of miRNA sequencing data and compilation of the obtained results have continued. Identification of correlations with bacterial DNA sequencing data which is necessary for further stages of the project is in progress. Preparation of research article is ongoing. Processing of human gut microbiome samples and preparation for sequencing have continued as well as metagenomic sequencing of the samples has initiated.

Information published 30.12.2020.

Progress of the project:

1 January 2021 – 31 March 2021

Analysis of miRNA sequencing data, compilation of the obtained results as well as the identification of correlations with bacterial DNA sequencing data have continued. A manuscript describing the differentially abundant miRNA in various experimental groups and their relation with the composition of gut microbiome has been prepared. Processing of human gut microbiome samples and metagenomic sequencing of the samples continues.

Information published 31.03.2021.

Progress of the project:

1 April 2021 – 30 June 2021

A manuscript describing the differentially abundant miRNAs in the samples of gut mucosa and feces and their relation with the composition of the gut microbiome has been submitted. Processing of human gut microbiome samples and metagenomic sequencing of the samples continues. Analysis of the obtained metagenomic data is ongoing. The investigation of differentially abundant miRNAs in the biological samples of study participants has initiated.

Information published 30.06.2021.

Progress of the project:

1 July 2021 – 30 September 2021

Analysis of metagenome data obtained by sequencing different biological material samples has continued. The investigation of differentially abundant miRNAs in the biological samples of study participants, as well as analysis of these data, is ongoing. Preparation of manuscript describing the miRNAs represented in human gut microbiome samples and their relation with the microbiome has been initiated. Designing of an animal experiment for functional validation of the results obtained is in process.

Information published 30.09.2021.

Progress of the project:

1 October 2021 – 31 December 2021

Investigation of differentially abundant miRNAs in the biological samples of study participants, and analysis of these data, are in progress. Preparation of manuscript describing the miRNAs represented in human gut microbiome samples and their relation with the microbiome continues. An animal experiment has been designed to validate the obtained results functionally. Project describing the planned animal study has been prepared and reviewed by Ethical Committee on Animal Experimentation of Food and Veterinary Service. Preparation for the animal study is in process.

Information published 30.12.2021.

Progress of the project:

1 January 2022 – 31 March 2022

Analysis of differentially abundant miRNAs obtained by sequencing biological material samples of study participants has continued. Preparation of manuscript describing the miRNAs represented in the gut microbiome samples and their relation with the microbiome is in process. An animal experiment is ongoing in which the effect of candidate miRNAs on the gut microbiome and disease manifestations are tested. Samples collected during the experiment are processed and sequenced. A manuscript describing the results obtained in this experiment is being prepared.

Information published 31.03.2022.