A <i>dietary carbohydrate – gut Parasutterella – human fatty acid biosynthesis</i> metabolic axis in obesity and type 2 diabetes

Abstract

Recent rodent microbiome experiments suggest that besides <i>Akkermansia, Parasutterella sp</i>. are important in type 2 diabetes and obesity development. In the present translational human study, we aimed to characterize <i>Parasutterella</i> 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 <i>Parasutterella</i> abundance in response to a weight loss intervention (n = 55). <i>Parasutterella</i> 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 <i>Parasutterella</i> abundance. This is of interest, since <i>Parasutterella</i> 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 <i>Parasutterella</i> 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 <i>Parasutterella</i> abundance during our weight loss intervention. Together, these data indicate a role for <i>Parasutterella</i> 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.