Meal-induced inflammation: postprandial insights from the Personalised REsponses to DIetary Composition Trial (PREDICT) study in 1000 participants

Authors: MAZIDI, MOHSEN - King'S College; VALDES, ANA - University Of Nottingham; ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; HALL, WENDY - King'S College; PUJOL, JOAN - Zoe Global Limited; WOLF, JONATHAN - Zoe Global Limited; HADJIGEORGIOU, GEORGE - Zoe Global Limited; SEGATA, NICOLA - University Of Trento, Italy; SATTAR, NAVEED - University Of Glasgow; KOIVULA, ROBERT - University Of Oxford; SPECTOR, TIM - King'S College; FRANKS, PAUL - King'S College; BERRY, SARAH - King'S College

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/1/2021
Publication Date: 6/8/2021
Citation: Mazidi, M., Valdes, A.M., Ordovas, J.M., Hall, W.L., Pujol, J.C., Wolf, J., Hadjigeorgiou, G., Segata, N., Sattar, N., Koivula, R., Spector, T.D., Franks, P.W., Berry, S.E. 2021. Meal-induced inflammation: postprandial insights from the Personalised REsponses to DIetary Composition Trial (PREDICT) study in 1000 participants. American Journal of Clinical Nutrition. 114(3):1028-1038. https://doi.org/10.1093/ajcn/nqab132.
DOI: https://doi.org/10.1093/ajcn/nqab132

Interpretive Summary: Eating produces significant metabolic changes, some of them related to an acute inflammatory response. In some individuals, this response is greater than others and depends on the foods ingested. Therefore, acutely elevated post-meal inflammation may contribute to chronic inflammation and associated diseases in some individuals. The purpose of this work, conducted by an international team including investigators at the HNRCA in Boston, was to characterize the variability in postprandial inflammatory responses using traditional and novel biomarkers of inflammation and dissect their biological determinants with a focus on the post-meal elevation of blood glucose and lipid levels. The analyses revealed that individuals showing enhanced post-meal inflammatory responses had higher predicted cardiovascular disease risk using traditional atherosclerotic disease risk scores than those who did not have such elevated responses. Specifically, the data highlighted the importance of modulating blood triglyceride levels in concert with obesity to reduce inflammation and thus prevent chronic diseases.

Technical Abstract: BACKGROUND: Meal-induced metabolic changes trigger an acute inflammatory response, contributing to chronic inflammation and associated diseases. OBJECTIVES: We aimed to characterize variability in postprandial inflammatory responses using traditional (IL-6) and novel [glycoprotein acetylation (GlycA)] biomarkers of inflammation and dissect their biological determinants with a focus on postprandial glycemia and lipemia. METHODS: Postprandial (0-6 h) glucose, triglyceride (TG), IL-6, and GlycA responses were measured at multiple intervals after sequential mixed-nutrient meals (0 h and 4 h) in 1002 healthy adults aged 18-65 y from the PREDICT (Personalised REsponses to DIetary Composition Trial) 1 study, a single-arm dietary intervention study. Measures of habitual diet, blood biochemistry, gut microbiome composition, and visceral fat mass (VFM) were also collected. RESULTS: The postprandial changes in GlycA and IL-6 concentrations were highly variable between individuals. Participants eliciting an increase in GlycA and IL-6 (60% and 94% of the total participants, respectively) had mean 6-h increases of 11% and 190%, respectively. Peak postprandial TG and glucose concentrations were significantly associated with 6-h GlycA (r = 0.83 and r = 0.24, respectively; both P < 0.001) but not with 6-h IL-6 (both P > 0.26). A random forest model revealed the maximum TG concentration was the strongest postprandial TG predictor of postprandial GlycA and structural equation modeling revealed that VFM and fasting TG were most strongly associated with fasting and postprandial GlycA. Network Mendelian randomization demonstrated a causal link between VFM and fasting GlycA, mediated (28%) by fasting TG. Individuals eliciting enhanced GlycA responses had higher predicted cardiovascular disease risk (using the atherosclerotic disease risk score) than the rest of the cohort. CONCLUSIONS: The variable postprandial increases in GlycA and their associations with TG metabolism highlight the importance of modulating TG in concert with obesity to reduce GlycA and associated low-grade inflammation-related diseases.