The rising prevalence of food allergies (FA) in the past decades is in parallel with growing obesity and diabetes epidemics, first in developed countries and now across the world. It raises the question whether maternal metabolic disorders are etiologically related to the rising prevalence of FA in children? Research findings from us and others have lent support that maternal metabolic disorders may increase the risk of child FA. However, the underlying molecular mechanisms are not well studied. Besides, it is well-observed that risk of developing FA varies greatly across individual children, even after controlling for maternal metabolic conditions. This raises another question: To what degree can early life environment and/or genetic factors modify the associations between maternal metabolic conditions and child development of FA? This proposal, highly motivated by our intriguing previous work and promising preliminary data, aims to systematically investigate the longitudinal relationships of maternal and cord blood metabolome (a comprehensive characterization of maternal and fetal circulating metabolites) with child development of FA in the Boston Birth Cohort (BBC). We will leverage the BBC?s extensive clinical and epidemiological databases, FA phenotypes, along with existing maternal and cord metabolomic and genome-wide genotype data from 1,500 mother-infant pairs (including 300 children with FA). We propose to address the following three novel specific aims:
Aim 1. To examine prospective associations of maternal and cord blood metabolome with child development of FA. We hypothesize that unfavorable maternal and cord blood metabolome profiles can independently and jointly increase child FA risk. We will further explore whether the identified FA-associated metabolites can explain or modify the impact of maternal metabolic disorders on child FA risk.
Aim 2. To examine the role of infant feeding pattern in the relationships between maternal and cord metabolome and child development of FA. We hypothesize that infant feeding pattern (including breastfeeding and duration, and the timing and type of solid food introduction) may modify the associations observed in Aim 1.
Aim 3. To explore the role of fetal genome in the associations observed in Aims 1 and 2. Finally, we seek to integrate multi-dimensional data (epidemiological, clinical, metabolomic and genomic data) to better characterize newborns? future risk for development of FA. This would be the first large-scale prospective birth cohort study to integrate cutting-edge metabolomics to address critical questions about early-life metabolic origins of FA under a life course frame. As such, our proposal is well-poised to gaining new insight on early metabolic risk of FA and to identify novel metabolite biomarkers in the pathways from maternal metabolic disorders to child development of FA. Such information will improve our ability to identify newborns at high risk of developing FA and implement more effective personalized intervention to mitigate FA risk at the earliest developmental windows.
Public relevance Food Allergy (FA) has emerged as a major clinical and public health problem worldwide. This project aims to investigate maternal metabolomic profile (to reflect the in-utero metabolic environment) and cord blood metabolomic profile (to reflect the fetal metabolic environment) in relation to FA development in the offspring, as well as the potential modification effects by infant feeding pattern and fetal genetic susceptibility, in a well- established U.S urban low-income minority prospective birth cohort. Findings from this study may help to discover novel biomarkers that can be used to identify newborns at high-risk of future FA development so that effective personalized interventions can be initiated to halt or reverse the risk trajectory during critical developmental periods.
