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EARLY LIFE INFECTION IS ASSOCIATED WITH PROINFLAMMATORY, ATHEROGENIC, AND DIABETOGENIC METABOLOMIC AND LIPIDOMIC PROFILES AT 12 MONTHS OF AGE
Abstract
Background and Aims
Infection is linked to later cardiometabolic disease, but the mechanisms are poorly understood, particularly in early life when most infection occurs. We investigated the relationship of infectious burden (from birth to 12 months) with NMR metabolomic and LC/MS lipidomic profiles at 12 months of age, and whether inflammation mediated these effects.
Methods
Plasma metabolomics and lipidomics were quantified in 12-month plasma from 555 infants in the Barwon Infant Study who had complete data on parent-reported infections in the first year of life. In linear regression models adjusted for confounders, the exposure was total number of infections as a continuous variable, and outcomes were 12-month metabolomic and lipidomic measures. We investigated whether inflammation (glycoprotein acetyls (GlycA) and high-sensitivity C-reactive protein (hsCRP)) mediated effects using structural-equation modeling.
Results
More infections were associated with higher inflammation markers and phenylalanine; and with lower high-density lipoprotein cholesterol, apolipoprotein A1, and docosahexaenoic acid. In lipidomic analysis, more infections were associated with higher phosphatidylethanolamines and lower plasmalogens; and lower ceramide and hexosylceramides species. Higher 12-month GlycA was associated with similar, more pronounced profiles. GlycA mediated a substantial proportion of the associations between infections and metabolomic and lipidomic measures (9.2-39.9%). hsCRP showed little evidence of mediating the relationship between infections and metabolomic or lipidomic measures. differences.
Conclusions
Higher infectious burden in infancy is associated with pro-inflammatory, pro-atherogenic, and diabetogenic metabolomic and lipidomic profiles. Inflammation may partly mediate the metabolic effects of infection. These findings suggest potentially modifiable pathways linking early life infection, inflammation, and cardiometabolic risk.