Project Summary/Abstract
Human milk provides significant health benefits for infants. Beyond nutrients, breastmilk contains antibodies for
immunity, growth factors associated with gut epithelial maturation, bacteria for establishment of the gut
microbiome, and metabolites that modulate inflammation. These important elements of human milk support
strong immune system development within the infant gut and better infant health. Unfortunately, many parents
aiming to breastfeed will supplement or wean earlier than planned and frequently report perceived low milk
supply as the reason. Increased mammary epithelium permeability (IMEP), as indicated by elevated milk
sodium, is a physiologic condition that could have significant implications for milk secretion, composition and
infant health. Lactation physiology studies have established that closed paracellular pathways, i.e., low
permeability, are essential for the establishment and maintenance of adequate milk secretion. Human studies
on permeability have focused on the period of secretory activation and persistent mammary epithelium
permeability at day 7 postpartum has been associated with perceived low milk supply. However, little is known
about IMEP during established lactation. We recently reported that IMEP among US women is more common
across lactation than previously recognized. Longitudinal US studies are needed to quantify mammary
epithelium permeability during established lactation and to investigate the extent to which increased
permeability influences lactation insufficiency. Our overall goal is to establish a clinically relevant robust
IMEP threshold, based on our analysis of sodium as a continuous variable, and determine the extent to
which IMEP is associated with suboptimal lactation outcomes and reduced infant health. We propose
that IMEP is associated with low milk supply and earlier than desired weaning. We also posit that IMEP results
in altered milk nutrient content, shifted inflammatory profiles and milk microbiome composition impacting the
infant gut immune profile and microbiome. We will enroll a diverse cohort of 400 mother-infant dyads from New
Mexico and Massachusetts. Participants will provide bilateral milk and infant fecal samples at four timepoints
spanning transitional, early and mature milk. Understanding the extent of IMEP linkage to suboptimal lactation
outcomes and infant intestinal health is of major importance because IMEP can be measured, treated and
prevented. Interventions to limit IMEP could include behavioral and dietary changes, as well as medications or
supplements. This will be the first study to determine the prevalence of IMEP and associated changes in milk
throughout the first five months postpartum, and the only large US cohort study of IMEP. Results from this
study could lead to a major change in clinical practice. Assessment of IMEP in milk could become routine,
especially among women seeking lactation counseling, and this may lead to improved outcomes. We expect
that our geographically and ethnically diverse cohorts will provide novel data on differences in risk factors for
IMEP with implications for lactation outcomes.