Enteropathy Markers in Early Life Were Associated with Adipokine, Apolipoprotein, and Cytokine Profiles Consistent with an Adverse Cardiometabolic Disease Risk Profile Later in Childhood in a Peruvian Birth Cohort

Abstract

Metabolic syndrome is a cluster of risk factors for cardiovascular disease afflicting more than 1 billion people worldwide and is increasingly being identified in younger age groups and in socioeconomically disadvantaged settings in the global south. Enteropathogen exposure and environmental enteropathy in infancy may contribute to metabolic syndrome by disrupting the metabolic profile in a way that is detectable in cardiometabolic markers later in childhood. A total of 217 subjects previously enrolled in a birth cohort in Amazonian Peru were monitored annually from ages 2 to 5 years. A total of 197 blood samples collected in later childhood were analyzed for 37 cardiometabolic biomarkers, including adipokines, apolipoproteins, cytokines, which were matched to extant early-life markers of enteropathy ascertained between birth and 2 years. Multivariate and multivariable regression models were fitted to test for associations, adjusting for confounders. Fecal and urinary markers of intestinal permeability and inflammation (myeloperoxidase, lactulose, and mannitol) measured in infancy were associated with later serum concentrations of soluble CD40-ligand, a proinflammatory cytokine correlated with adverse metabolic outcomes. Fecal myeloperoxidase was also associated with later levels of omentin-1. Enteric protozoa exposure showed stronger associations with later cardiometabolic markers than viruses, bacteria, and overall diarrheal episodes. Early-life enteropathy markers were associated with altered adipokine, apolipoprotein, and cytokine profiles later in childhood consistent with an adverse cardiometabolic disease risk profile in this cohort. Markers of intestinal permeability and inflammation measured in urine (lactulose, mannitol) and stool (myeloperoxidase, protozoal infections) during infancy may predict metabolic syndrome in adulthood.

ApoE Mimetic Peptides to Improve the Vicious Cycle of Malnutrition and Enteric Infections by Targeting the Intestinal and Blood-Brain Barriers

“…In addition, this review aims to broaden our understanding of how tropical/environmental enteropathy in children negatively affects their cognitive and physical development as a function of APOE genotypes by disturbing the gut-brain axis. Such insults may cause long-term developmental deficits in growing children when occurring at key times of microbiota and brain development, which could increase the risk for neurodegenerative and metabolic disorders later in life [10][11][12]. The pursuit of novel apoE mimetic peptides that target the intestinal and brain barriers for interrupting this vicious cycle of malnutrition and enteric infections, especially in more genetically predisposed children (thriving under adverse environments), may lead to novel and effective therapies for precision medicine in the field of childhood infectious diseases.…”