Description and Comparison of Biological Vulnerability in Small Vulnerable Newborns Versus Healthy Community Controls in Urban Burkina Faso

Overview

The aim of the DenBalo study is to apply integrated multi-omics methods to examine the biological mechanisms underlying this vulnerability in Small Vulnerable Newborns (SVNs) in LMICs, with the ultimate goal of identifying targeted interventions to reduce morbidity and mortality in this high-risk population. The evidence generated from this project will ultimately help promote healthy pregnancies and the birth of healthy babies. To achieve this goal, three research objectives are proposed: 1. To describe and compare gut microbiota, immune system and breastmilk components in SVNs versus healthy community controls in urban Burkina Faso. 2. To describe and compare the development of the gut microbiota, the immune system and breastmilk components during the first six months of life in SVNs versus healthy community controls in urban Burkina Faso. 3. To investigate the relationship between the composition of the gut microbiota, the immune system and breastmilk components during the first six months of life in SVNs versus healthy community controls in urban Burkina Faso.

The first days and weeks of life are characterized by a truly impressive cascade of biological processes that drive neonatal growth and development-all of which are crucial to preparing the newborn for life outside the womb. First, vaginal delivery exposes neonates to an important natural microbial inoculum from the vaginal microbiota in labor and from the maternal intestinal microbiota at birth. Together, these early colonization events lay the foundation for gut microbiota assembly, inform the arrival of subsequent species through microbial interactions, and dictate infant microbiota maturation. A recent study has shown that a handful of bacteria begin colonizing the infant gut within the first days of life, that gut microbes accumulate gradually over time, and that pioneer strains are retained after a month of life. Whether the gut microbial assembly, maturation, and functional potential differs between SVNs versus healthy, community controls, or is coupled to growth and development, remains unresolved. Secondly, the first days and weeks of life represent a time of heightened vulnerability to infectious disease. Neonatal infections account for a tragic 40% of mortality in children under five years of age. This critical time period is increasingly seen as a key determinant in health over the entire lifespan. A recent study using a high-dimensional, unbiased approach to characterize neonatal immune system development reported a dramatic, purposeful trajectory in the first week of life. While much remains to be explored, what is known is that early microbial colonization is vital to optimal host immune development and protection from disease and that, after birth, the most important determinant of infant gut colonization is breastfeeding. The impacts of preterm birth, low birth weight, or small for gestational age on immune development and function remain enigmatic and the mediating effect of the gut microbiome unknown. Thirdly, neonatal nutrition plays a vital role in the two aforementioned processes-because breastfeeding both initiates tropic priming of the newborn gut and transfers numerous immunological factors to the baby. However, few studies have explored the synergy between neonatal microbiome and immunome development, and even fewer through the lens of newborn nutrition. Moreover, virtually zero studies include an integrated characterization of these processes in the SVN. Evidence suggests that, compared to mothers of full-term neonates, the colostrum from mothers of preterm newborns has higher protein and fat content, free amino acids, sodium, and bioactive milk components including HMOs, cytokines, and lactoferrin. But because few studies have evaluated the association between early milk composition and infant growth and development, it is unclear which components are most imperative for a healthy gut microbiota and a robust immune system, particularly in the SVN. Major advances in systems biology approaches allowing for unbiased, integrated analyses of high-dimensional -omic databases have provided the critical bioinformatic toolkit required to address these questions. Indeed, the ground has never been more fertile for a step-change in commitment to high-impact research on neonatal microbiome and immunome development and the synergy with newborn nutrition.