Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, Virginia.
Department of Emergency Medicine, Chi-Mei Medical Center, Tainan, Taiwan.
Am J Trop Med Hyg. 2022 Sep 12;107(4):754-765. doi: 10.4269/ajtmh.21-1024. Print 2022 Oct 12.
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.
代谢综合征是一组心血管疾病风险因素，影响着全球超过 10 亿人，并且在全球南方的年轻人群体和社会经济弱势群体中日益增多。婴儿时期的病原体暴露和环境肠病可能通过以一种在儿童后期的心脏代谢标志物中可检测到的方式扰乱代谢谱，从而导致代谢综合征。共有 217 名先前在亚马逊秘鲁出生队列中登记的受试者在 2 至 5 岁时每年进行监测。在儿童后期共采集了 197 份血液样本，用于分析 37 种心脏代谢生物标志物，包括脂肪因子、载脂蛋白、细胞因子，这些标志物与出生至 2 岁期间确定的早期生活肠病的现有标志物相匹配。采用多元和多变量回归模型来检验相关性，同时调整了混杂因素。婴儿期测量的肠道通透性和炎症的粪便和尿液标志物（髓过氧化物酶、乳果糖和甘露醇）与后期血清可溶性 CD40 配体浓度相关，该标志物是与不良代谢结果相关的促炎细胞因子。粪便髓过氧化物酶也与后期的网膜素-1水平相关。肠原生动物暴露与后期心脏代谢标志物的相关性强于病毒、细菌和总体腹泻发作。早期生活肠病标志物与儿童后期的脂肪因子、载脂蛋白和细胞因子谱的改变相关，这与该队列中不良心脏代谢疾病风险特征一致。在婴儿期尿液（乳果糖、甘露醇）和粪便（髓过氧化物酶、原生动物感染）中测量的肠道通透性和炎症标志物可能预测成年期的代谢综合征。
