Characterization of specific Gut Bacteria and bacterial Metabolites in Human Obesity and Type 2 Diabetes

In the present thesis, we aimed to characterize the gut bacterium Parasutterella in our cross-sectional FoCus cohort (n=1,544), an independent Canadian cohort (n=438) and additionally in a weight loss intervention cohort (n=55). Parasutterella was positively associated with BMI (body mass index), fasting insulin and type 2 diabetes independently of low-grade inflammation. Dietary analysis revealed a positive association between Parasutterella sp. with the dietary intake of carbohydrates but not with fat or protein consumption. MS-metabolomics analysis appointed L-cysteine as strongly reduced in subjects with high Parasutterella abundance. Additionally, metabolic network enrichment analysis identified an association of high Parasutterella abundance with the activation of the human fatty acid biosynthesis pathway suggesting a mechanism for body weight gain. This was supported by a reduction of Parasutterella excrementihominis abundance during a low-carb diet within the weight loss intervention. Together, these data indicate a role of Parasutterella in human obesity and type 2 diabetes. Secondly, the present thesis shows by biostatistical modeling that agmatine, measured by MS-metabolomics, was elevated in FoCus subjects with an increased BMI (n=1,704) coupled with reduced microbial α-diversity. In addition, cell culture models provided insight into the effect of agmatine on decelerating adipogenesis and activating inflammatory processes in human macrophages. These results suggest that agmatine has effects on metabolic processes and these should be validated in future clinical interventions.


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