A metabolic axis in obesity and type 2 diabetes.

Recent rodent microbiome experiments suggest that besides . are important in type 2 diabetes and obesity development. In the present translational human study, we aimed to characterize in our European cross-sectional FoCus cohort (n = 1,544) followed by validation of the major results in an independent Canadian cohort (n = 438). In addition, we examined abundance in response to a weight loss intervention (n = 55). was positively associated with BMI and type 2 diabetes independently of the reduced microbiome α/β diversity and low-grade inflammation commonly found in obesity. Nutritional analysis revealed a positive association with the dietary intake of carbohydrates but not with fat or protein consumption. Out of 126 serum metabolites differentially detectable by untargeted HPLC-based MS-metabolomics, L-cysteine showed the strongest reduction in subjects with high abundance. This is of interest, since is a known high L-cysteine consumer and L-cysteine is known to improve blood glucose levels in rodents. Furthermore, metabolic network enrichment analysis identified an association of high abundance with the activation of the human fatty acid biosynthesis pathway suggesting a mechanism for body weight gain. This is supported by a significant reduction of the abundance during our weight loss intervention. Together, these data indicate a role for in human type 2 diabetes and obesity, whereby the link to L-cysteine might be relevant in type 2 diabetes development and the link to the fatty acid biosynthesis pathway for body weight gain in response to a carbohydrate-rich diet in obesity development.