Work

Influence of Gut Microbial Communities on Fasting and Postprandial Lipids and Circulating Metabolites: The PREDICT 1 Study

Year: 2020

Type: article

Abstract: The human gut microbiome plays a critical role in host glucose metabolism, but its connections to other key markers of cardiometabolic health in fasting and postprandial conditions is largely unknown. The PREDICT 1 study enrolled n = 1,102 twins and unrelated healthy US/UK adults to explore the genetic, metabolic, microbial, and meal determinants of fasting metabolites and postprandial responses to foods. This multi-centre dietary study assessed fasting and postprandial (0-6h) circulating metabolites over a 13d study period incorporating standardized test meals of varying nutrient composition. Shotgun metagenomics was performed from samples collected at baseline (n = 1,001 UK and 97 US). Metabolomics (NMR) was performed on clinic fasting and postprandial samples, blood glucose was continuously assessed, and blood triglycerides and C-peptide were serially measured. Using machine learning models, we found the fasting metabolites most strongly associated with overall gut community structure were the inflammatory marker GlycA (r = 0.31), and HDL and VLDL particle diameter (HDL-D and VLDL-D; r = 0.3 and 0.28 respectively). Variance explained was slightly greater for postprandial HDL-D and VLDL-D (at 6h; r = 0.32 and 0.31, respectively) than fasting levels, whilst the other metabolites did not differ (e.g., GlycA r = 0.28). Lipid-mediated metabolites were more closely associated with the gut microbiome in both fasting and postprandial states compared with glycemic-mediated measurements. There were distinct microbial clusters that segregated both fasting and postprandial metabolites according to their known association with cardiometabolic disease; ApoA and HDL vs. ApoB, VLDL, IDL LDL, remnant C, GlycA, IL-6, blood pressure, glucose, insulin and HbA1c. We also identified differential abundance among several microbes associated with metabolic health, including Prevotella copri and Faecalibacterium prausnitzii. Results obtained in the UK cohort were validated in the US cohort. An individual's gut microbial composition is predictive of their cardiometabolic markers and personalized responses to food. Our data highlight the potential of the gut microbiome as a target amenable to modulation in personalized nutrition to ameliorate cardiometabolic risk. Zoe Global Ltd., NIHR GSTT BRC, Wellcome Trust.

Source: Current Developments in Nutrition

DOI: 10.1093/cdn/nzaa062_004