Ar metformīna lietošanu asociētas izmaiņas cilvēka zarnu mikrobioma sastāvā un DNS metilēšanas profilos
Date
2017
Authors
Elbere, Ilze
Journal Title
Journal ISSN
Volume Title
Publisher
Latvijas Universitāte
Abstract
Metformīns ir pirmās izvēles medikaments 2. tipa cukura diabēta ārstēšanā. Tam raksturīga variabilitāte terapijas efektivitātē un biežas blaknes. Medikamenta iedarbību var ietekmēt tādi faktori kā mijiedarbība ar zarnu mikrobiomu un gēnu ekspresijas regulācija DNS metilēšanas līmenī. Maģistra darba mērķis bija noskaidrot, kādas izmaiņas metformīns ierosina cilvēka zarnu mikrobioma kompozīcijā un leikocītu metilēšanas profilā. Darbā tika veikta 16S rRNS amplikonu analīze 18 metformīna lietotāju fēču paraugos un DNS metilēšanas novērtēšana 12 indivīdiem. Metformīna ierosinātas izmaiņas gan zarnu mikrobiomā, gan metilēšanas profilā tika novērotas jau pirmo 24 stundu laikā, daļēji skaidrojot iespējamos blakņu cēloņus un pozitīvo efektu pamatā esošos mehānismus. Darbs izstrādāts 06.2015. – 05.2017. Latvijas Biomedicīnas pētījumu un studiju centrā.
Metformin is a first line agent for treatment of type 2 diabetes. It has high efficacy variability and side effects are common. The effect of medicament can be influenced by such factors as interaction with gut microbiome and regulation of gene expression via DNA methylation. The aim of this work was to investigate the impact of metformin on composition of gut microbiome and methylation profile of leucocytes. Fecal samples from 18 participants were used in 16S rRNA analysis and DNA methylation was evaluated in 12 individuals. Metformin induced changes in gut microbiome and methylation profiles were observed within the first 24 hours, thus partly explaining the possible causes for side effects and mechanisms of positive effects. The work was carried out in the Latvian Biomedical Research and Study Centre during the period 06.2015 – 05.2017.
Metformin is a first line agent for treatment of type 2 diabetes. It has high efficacy variability and side effects are common. The effect of medicament can be influenced by such factors as interaction with gut microbiome and regulation of gene expression via DNA methylation. The aim of this work was to investigate the impact of metformin on composition of gut microbiome and methylation profile of leucocytes. Fecal samples from 18 participants were used in 16S rRNA analysis and DNA methylation was evaluated in 12 individuals. Metformin induced changes in gut microbiome and methylation profiles were observed within the first 24 hours, thus partly explaining the possible causes for side effects and mechanisms of positive effects. The work was carried out in the Latvian Biomedical Research and Study Centre during the period 06.2015 – 05.2017.
Description
Keywords
Bioloģija , metformīns , zarnu mikrobioms , 16S rRNS , DNS metilēšana , cukura diabēts