Characterisation of fasting and postprandial NMR metabolites: insights from the ZOE PREDICT 1 study

Authors: BERMINGHAM, KATE - King'S College; MAZIDI, MOHSEN - King'S College; FRANKS, PAUL - Lund University; MAHER, TYLER - King'S College; VALDES, ANA - University Of Nottingham; LINENBERG, INBAR - King'S College; WOLF, JONATHAN - Zoe Global Limited; HADJIGEORGIOU, GEORGE - Zoe Global Limited; SPECTOR, TIM - King'S College; MENNI, CRISTINA - King'S College; ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; BERRY, SARAH - King'S College; HALL, WENDY - King'S College

Submitted to: Nutrients
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/18/2023
Publication Date: 6/5/2023
Citation: Bermingham, K.M., Mazidi, M., Franks, P.W., Maher, T., Valdes, A.M., Linenberg, I., Wolf, J., Hadjigeorgiou, G., Spector, T.D., Menni, C., Ordovas, J.M., Berry, S.E., Hall, W.L. 2023. Characterisation of fasting and postprandial NMR metabolites: insights from the ZOE PREDICT 1 study. Nutrients. https://doi.org/10.3390/nu15112638.
DOI: https://doi.org/10.3390/nu15112638

Interpretive Summary: The study focuses on understanding how different individuals' bodies react to food by tracking changes in metabolites, which are substances produced by metabolism, after eating. This research took measurements of 250 metabolites before and after participants consumed a standard meal. The findings showed that the levels of most metabolites changed after eating, with about half increasing and half decreasing. Some of the biggest changes were seen in substances related to fat particles and ketone bodies, compounds produced when the body breaks down fat for energy. Interestingly, these post-meal changes were highly individual, indicating that everyone's body might process food differently. These results are potentially significant for the field of personalized nutrition. They suggest that monitoring individuals' metabolite responses to meals could offer a new way of tailoring dietary advice to the needs of the individual, thereby improving health outcomes. This, in turn, could lead to more effective use of resources in public health and food-related industries.

Technical Abstract: Background: Postprandial metabolomic profiles and their inter-individual variability are not well characterised. Here, we describe postprandial metabolite changes, their correlations with fasting values and their inter- and intra-individual variability, following a standardised meal in the ZOE PREDICT 1 cohort. Methods: In the ZOE PREDICT 1 study (n = 1002 (NCT03479866)), 250 metabolites, mainly lipids, were measured by a Nightingale NMR panel in fasting and postprandial (4 and 6 h after a 3.7 MJ mixed nutrient meal, with a second 2.2 MJ mixed nutrient meal at 4 h) serum samples. For each metabolite, inter- and intra-individual variability over time was evaluated using linear mixed modelling and intraclass correlation coefficients (ICC) were calculated. Results: Postprandially, 85% (of 250 metabolites) significantly changed from fasting at 6 h (47% increased, 53% decreased; Kruskal-Wallis), with 37 measures increasing by >25% and 14 increasing by >50%. The largest changes were observed in very large lipoprotein particles and ketone bodies. Seventy-one percent of circulating metabolites were strongly correlated (Spearman's rho >0.80) between fasting and postprandial timepoints, and 5% were weakly correlated (rho <0.50). The median ICC of the 250 metabolites was 0.91 (range 0.08-0.99). The lowest ICCs (ICC < 0.40, 4% of measures) were found for glucose, pyruvate, ketone bodies (beta-hydroxybutyrate, acetoacetate, acetate) and lactate. Conclusions: In this large-scale postprandial metabolomic study, circulating metabolites were highly variable between individuals following sequential mixed meals. Findings suggest that a meal challenge may yield postprandial responses divergent from fasting measures, specifically for glycolysis, essential amino acid, ketone body and lipoprotein size metabolites.