Open AccessAssociation of metformin administration with gut microbiome dysbiosis in healthy volunteers
Author(s) -
Ilze Elbere,
Ineta Kalniņa,
Ivars Silamiķelis,
Ilze Konrāde,
Linda Zaharenko,
Kristine Sekace,
Ilze Radoviča-Spalviņa,
Dāvids Fridmanis,
Dita Gudrā,
Valdis Pīrāgs,
Jānis Kloviņš
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0204317
Subject(s) - metformin , gut flora , dysbiosis , microbiome , type 2 diabetes , feces , medicine , biology , bacteroides , physiology , diabetes mellitus , microbiology and biotechnology , immunology , bioinformatics , endocrinology , insulin , genetics , bacteria
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 the gut microbiome was analyzed by massive parallel sequencing of 16S rRNA gene (V3 region). Results There was a significant reduction of inner diversity of gut microbiota observed already 24 hours after metformin administration. We observed an association between the severity of gastrointestinal side effects and the increase in relative abundance of common gut opportunistic pathogen Escherichia-Shigella spp. One week long treatment with metformin was associated with a significant decrease in the families Peptostreptococcaceae and Clostridiaceae _1 and four genera within these families. Conclusions Our results are in line with previous findings on the capability of metformin to influence gut microbiota. However, for the first time we provide evidence that metformin has an immediate effect on the gut microbiome in humans. It is likely that this effect results from the increase in abundance of opportunistic pathogens and further triggers the occurrence of side effects associated with the observed dysbiosis. An additional randomized controlled trial would be required in order to reach definitive conclusions, as this is an exploratory study without a placebo control arm. Our findings may be further used to create approaches that improve the tolerability of metformin.