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Search for gut microbiota-associated biomarkers involved in the pathogenesis of T2D

T2D is a highly prevalent metabolic disease worldwide, including in Japan. It has been estimated that ~20 million Japanese, as many as 1 out of 5 individuals, suffer from diabetic or prediabetic (medically defined as glucose intolerance) conditions. Therefore, prevention of T2D is an urgent need both socially and economically. To identify T2D-preventive biomarkers or factors involved in the pathogenesis of T2D, individuals with glucose intolerance should be carefully analyzed, instead of already diagnosed and treated T2D patients. To this end, as an IMS center project, we have been collaborating with the University of Tokyo Hospital and recruited three groups (n=100 each) of volunteers from those undergoing a complete medical checkup: 1) no abnormal examination outcome (control), 2) obesity (BMI ≥ 25), and 3) glucose intolerance (fasting blood glucose ≥ 110 mg/dl and HbA1c ≥ 6.0%) (Fig). In addition to the thorough clinical examination data taken during the medical checkup, the following have been collected in RIKEN: fecal metagenomic and metabolomic data, plasma and urine metabolomic data, CAGE-based RNAseq data of peripheral blood mononuclear cells, and whole genome sequencing data. We are also collecting nutritional and physical activity data using a brief self-administered diet history questionnaire and accelerometry, respectively.

Correlation analysis of clinical data with fecal metabolome and microbiome data has revealed that insulin resistance and metabolic syndrome were significantly associated with particular sugar derivatives, as were certain bacteria belonging to the family Lachnospiraceae among gut microbes.

figure of Correlating clinical and multi-omics data to identify biomarkers involved in the pathogenesis of type 2 diabetes mellitus

Figure: Correlating clinical and multi-omics data to identify biomarkers involved in the pathogenesis of type 2 diabetes mellitus.
The data in the bottom part of the figure are examples of fecal metabolome analyses.

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