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ABSTRACT: The alteration of salivary microbiome in periodontitis with or without type-2 diabetes mellitus and Metformin treatment

PROVIDER: PRJNA601054 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10882700.fastq.gz	Fastqsanger.gz
	SRR10882701.fastq.gz	Fastqsanger.gz
	SRR10882702.fastq.gz	Fastqsanger.gz
	SRR10882703.fastq.gz	Fastqsanger.gz
	SRR10882704.fastq.gz	Fastqsanger.gz

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Project description: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-naïve type 2 diabetes patient volunteers in vivo. Longitudinal blood-derived transcriptome analysis revealed metformin-induced differential expression of novel and previously described genes involved in cholesterol homeostasis (SLC46A1 and LRP1), cancer development (CYP1B1, STAB1, CCR2, TMEM176B) and immune responses (CD14, CD163) after administration of metformin for three months. We demonstrate for the first time transcriptome-based molecular discrimination between metformin responders (delta HbA1c ≥ 1% or 12.6 mmol/mol) and non-responders (delta HbA1c < 1% or 12.6 mmol/mol) determined by expression levels of 56 genes, explaining 13.9% of the variance in the therapeutic efficacy of the drug. Moreover, we found a significant upregulation of IRS2 gene (log2FC 0.89) in responders compared to non-responders before the use of metformin. Finally, we provide evidence for the mitochondrial respiratory complex I as one of the factors related to the high variability of the therapeutic response to metforminin patients with type 2 diabetes mellitus.

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Project description:Salivary exsomal miRNAs may play important role in the pathogenesis of chronic inflammatory disease, such as periodontitis. There are many studies which suggested the connection between periodontitis and systemic disease, however, the role of specific miRNA as a intersection of periontitis and diabetes are not elucidated. We suggested miR-25-3p as possible common mediator in the pathogenesis of periodontitis and diabetes.

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Expression data from mouse liver treated with metformin

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Project description:Background: Metformin, one of the first-line medication for the treatment of type 2 diabetes and gestational diabetes, has recently be suggested for targeting cardiovascular disease, cancer and aging. Therefore, current understanding of the mechanism of this drug is incompletely understood, and the function of multiple tissues, other than liver metabolism alone, may be influenced. Methods: The wildtype healthy mice treated with metformin were compared with controls (treated with double distilled water). The transcriptome changes with/without metformin treatment were probed by using high-throughput RNA-seq techniques Results: A comprehensive mouse transcriptome map with metformin treatment across ten tissues including aorta, eyeball, brain, adipose tissue, heart, kidney, liver, skeletal muscle, stomach and testis, was provided. Function enrichment, network characteristics and disease association of the differentially expressed genes were analyzed. We also compared our expression profiles with related microarray data in order to find conditions that share similar expression profiles with metformin treatment. Conclusions: This dataset could serve as a baseline resource for investigating the potential beneficial or adverse effects of metformin across different tissues.

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