0000000000442396
AUTHOR
Ilze Elbere
METFORMIN EFFECTS ON GUT MICROBIOME AND EPIGENETICS IN TYPE 2 DIABETES PATIENTS AND HEALTHY INDIVIDUALS
Metformīna farmakodinamika ir plaši pētīta, tomēr detaļas joprojām ir neskaidras. Šī pētījuma mērķis bija identificēt taksonomiskos un funkcionālos zarnu mikrobioma biomarķierus, kā arī saimniekorganisma epiģenētiskās iezīmes metformīna farmakodinamikai, terapijas efektivitātei un tolerancei. Izmantojot zarnu mikrobioma lielapjoma paralēlo sekvenēšanu, mēs novērojām metformīna terapijas izraisītu būtisku un tūlītēju iekšējās daudzveidības samazināšanos, kā arī taksonomiskā profila izmaiņas jaundiagnosticētiem T2D pacientiem un veseliem indivīdiem. Mēs prezentējām pirmsterapijas mikrobioma taksonomisko sastāvu kā rīku terapijas efektivitātes un tolerances prognozēšanai. Dati par globālajām D…
Epigenetic markers associated with metformin response and intolerance in drug-naïve patients with type 2 diabetes
Metformin is the first-line pharmacotherapy for managing type 2 diabetes (T2D). However, many patients with T2D do not respond to or tolerate metformin well. Currently, there are no phenotypes that successfully predict glycemic response to, or tolerance of, metformin. We explored whether blood-based epigenetic markers could discriminate metformin response and tolerance by analyzing genome-wide DNA methylation in drug-naïve patients with T2D at the time of their diagnosis. DNA methylation of 11 and 4 sites differed between glycemic responders/nonresponders and metformin-tolerant/intolerant patients, respectively, in discovery and replication cohorts. Greater methylation at these sites associ…
A widely used sampling device in colorectal cancer screening programmes allows for large-scale microbiome studies.
We read with interest the article by Passamonti et al ,1 reporting the performance of two different faecal immunochemical tests (FITs) highlighting the importance of standardisation and validation of screening methodologies. Conventionally, laboratory-based FIT is the preferred approach in testing for occult blood in faeces, which includes colorectal cancer screening programmes.2–4 The potential of preserving stable faecal samples in a widely used FIT buffer for microbiome research would enable prospective microbiome studies in generally healthy subjects undergoing colorectal cancer screening. For this purpose, we evaluated faecal sample stability in the commonly used OC-Sensor (Eiken Chemi…
Additional file 1: Table S1. of Next-generation-sequencing-based identification of familial hypercholesterolemia-related mutations in subjects with increased LDLâ C levels in a latvian population
All variants found in study group. (DOC 611Â kb)
Next-generation-sequencing-based identification of familial hypercholesterolemia-related mutations in subjects with increased LDL–C levels in a latvian population
Background Familial hypercholesterolemia (FH) is one of the commonest monogenic disorders, predominantly inherited as an autosomal dominant trait. When untreated, it results in early coronary heart disease. The vast majority of FH remains undiagnosed in Latvia. The identification and early treatment of affected individuals remain a challenge worldwide. Most cases of FH are caused by mutations in one of four genes, APOB, LDLR, PCSK9, or LDLRAP1. The spectrum of disease-causing variants is very diverse and the variation detection panels usually used in its diagnosis cover only a minority of the disease-causing gene variants. However, DNA-based tests may provide an FH diagnosis for FH patients…
Association of metformin administration with gut microbiome dysbiosis in healthy volunteers
Background Metformin is a widely used first-line drug for treatment of type 2 diabetes. Despite its advantages, metformin has variable therapeutic effects, contraindications, and side effects. Here, for the very first time, we investigate the short-term effect of metformin on the composition of healthy human gut microbiota. Methods We used an exploratory longitudinal study design in which the first sample from an individual was the control for further samples. Eighteen healthy individuals were treated with metformin (2 × 850 mg) for 7 days. Stool samples were collected at three time points: prior to administration, 24 hours and 7 days after metformin administration. Taxonomic composition of…
Antidiabētiskā medikamenta metformīna lietošanas ietekme uz cilvēka zarnu mikrobiomu
Metformīns ir plaši lietots medikaments 2. tipa cukura diabēta ārstēšanā. Pastāv hipotēze, ka metformīna ietekme uz organismu daļēji varētu tikt skaidrota ar tā mijiedarbību ar zarnu mikrobiomu. Bakalaura darba mērķis bija noskaidrot, kā metformīns ietekmē zarnu mikrobioma kompozīciju. Darba ietvaros tika izdalīta mikrobiālā DNS no astoņu cilvēku fēču paraugiem, kas bija ievākti dažādos laika posmos no metformīna lietošanas uzsākšanas, un, izmantojot lielapjoma paralēlo sekvenēšanu, veikta 16S rRNS V3 reģiona analīze, lai salīdzinātu mikrobioma kompozīciju. Pēc nedēļu ilgas metformīna lietošanas tika novērotas būtiskas izmaiņas vairāku taksonomisko vienību īpatsvarā un mikrobioma iekšējās d…
Whole-blood transcriptome profiling reveals signatures of metformin and its therapeutic response
Metformin, a biguanide agent, is the first-line treatment for type 2 diabetes mellitus due to its glucose-lowering effect. Despite its wide application in the treatment of multiple health conditions, the glycemic response to metformin is highly variable, emphasizing the need for reliable biomarkers. We chose the RNA-Seq-based comparative transcriptomics approach to evaluate the systemic effect of metformin and highlight potential predictive biomarkers of metformin response in drug-naive volunteers with type 2 diabetes in vivo. The longitudinal blood-derived transcriptome analysis revealed metformin-induced differential expression of novel and previously described genes involved in cholester…
Ar metformīna lietošanu asociētas izmaiņas cilvēka zarnu mikrobioma sastāvā un DNS metilēšanas profilos
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 ie…
Baseline gut microbiome composition predicts metformin therapy short-term efficacy in newly diagnosed type 2 diabetes patients
BackgroundThe study was conducted to investigate the effects of metformin treatment on the human gut microbiome's taxonomic and functional profile in the Latvian population, and to evaluate the correlation of these changes with therapeutic efficacy and tolerance.MethodsIn this longitudinal observational study, stool samples for shotgun metagenomic sequencing-based analysis were collected in two cohorts. The first cohort included 35 healthy nondiabetic individuals (metformin dose 2x850mg/day) at three time-points during metformin administration. The second cohort was composed of 50 newly-diagnosed type 2 diabetes patients (metformin dose-determined by an endocrinologist) at two concordant ti…