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Association of metformin administration with gut microbiome dysbiosis in healthy volunteers.

ABSTRACT: 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.

SUBMITTER: Elbere I

PROVIDER: S-EPMC6160085 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Association of metformin administration with gut microbiome dysbiosis in healthy volunteers.

Elbere Ilze I Kalnina Ineta I Silamikelis Ivars I Konrade Ilze I Zaharenko Linda L Sekace Kristine K Radovica-Spalvina Ilze I Fridmanis Davids D Gudra Dita D Pirags Valdis V Klovins Janis J

PloS one 20180927 9

<h4>Background</h4>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.<h4>Methods</h4>We used an exploratory longitudinal study design in which the first sample from an individual was the control for further samples. Eighteen healthy ind ...[more]

PMID: 30261008

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Project description:Object: Primary osteoporosis (PO) is the most common bone disease, which is characterized by decreased bone mass, damage of bone tissue microstructure, increased bone fragility, and is prone to fracture. Gut microbiome may be involved in bone metabolism of PO through gut-brain axis regulation of immune system and endocrine system, however, the specific mechanism is still unclear. The purpose of this study was to characterize the gut microbiome of patients with PO and its possible role in the occurrence and development of the disease. Methods: Fecal samples were collected from 48 PO patients and 48 healthy controls (HC). The composition of gut microbiome community was analyzed by 16s rDNA amplification sequencing, and the difference of gut microbiome composition between PO patients and HC individuals was compared. PICRUSt was also used to predict the biological function of gut microbiome in patients with PO, and to explore its possible role in the occurrence and development of this disease. The classification model is constructed by random forest algorithm so as to screen the key biomarkers. Result: The diversity of gut microorganisms in PO patients was significantly higher than that in HC group (p < 0.05) and there was significant difference in microbial composition in PO group. The abundance of Dialister (0.036 vs. 0.004, p < 0.001) and Faecalibacterium (0.331 vs. 0.132, p < 0.001) were significantly enriched which were the key flora related to PO. Although no significant correlation between bone mineral density and the richness of microbial communities are found, PICRUST results show that there are a wide range of potential pathways between gut microbiome and PO patients, including genetic information processing, metabolism, environmental information processing, cellular processes, human diseases, and organic systems. Notably, the discriminant model based on dominant microflora can effectively distinguish PO from HC (AUC = 93.56). Conclusions: The findings show that PO is related to the change of gut microbiome, especially the enriched Dialister and Faecalibacterium genera, which give new clues to understand the disease and provide markers for the diagnosis and new strategies for intervention treatment of the disease.

Dataset Information

Association of metformin administration with gut microbiome dysbiosis in healthy volunteers.

Publications

Association of metformin administration with gut microbiome dysbiosis in healthy volunteers.

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