Human Milk Proteins: An Interactomics and Updated Functional Overview

Abstract

Milk and milk fractions are characterized by a wide array of proteins, whose concentration spans across several orders of magnitude. By exploiting a combined approach based on functional gene ontology enrichment (FatiGO/Babelomics), hierarchical clustering, and pathway and network analyses, we merged data from literature dealing with protein-oriented studies on human milk. A total of 285 entries defined a nonredundant list upon comparison with the Ingenuity Knowledge Base from the Ingenuity Pathway Analysis software. Results were compared with an inventory of bovine milk proteins gathered from dedicated proteomic studies. A protein core of 106 proteins was found, with most of the entries associated to three main biological functions, namely nutrient transport/lipid metabolism, concretization of the immune system response and cellular proliferation processes. Our analyses confirm and emphasize that the biological role of the human milk proteins is not only limited to the provision of external nutrients and defense molecules against pathogens to the suckling but also to the direct stimulation of the growth of neonate tissues/organs and to the development of a proper independent immune system, both through the induction of a number of molecular cascades associated with cell proliferation/differentiation. The latter aspects were previously investigated by single-molecule dedicated studies, missing the holistic view that results from our analysis.

Comprehensive Proteomic Analysis of Human Milk-derived Extracellular Vesicles Unveils a Novel Functional Proteome Distinct from Other Milk Components

“…Supplemental File S2 contains the raw data from these eight studies and supplemental Table S1 contains an overview of the individual 38 studies. Data sets from Beck et al (22) and D'Alessandro et al (23), which summarized previous published work, were used instead of each individual study reviewed. Data sets were converted to the common gene name format in order to construct one data set that could be compared with our data set.…”

Mount Pinatubo, Inflammatory Cytokines, and the Immunological Ecology of Aeta Hunter-Gatherers

“…Yet maternal influences on development extend beyond birth; breast milk is the primary food source for all mammalian newborns and a medium of chemical messages (Bernt and Walker 1999). For example, milk delivers an array of bioactive molecules that not only confer immunoprotection but also shape the microbiome and physiology of the developing gastrointestinal tract (Rautava and Walker 2009;D'Alessandro et al 2010). Breast milk can also contain high concentrations of nonspecific defense factors that reflect a lifetime of maternal antigenic experiences, and the immunologic protection being conferred to an infant is often specific to local disease conditions (McDade and Worthman 1999).…”

Immune Components in Human Milk Are Associated with Early Infant Immunological Health Outcomes: A Prospective Three-Country Analysis

“…Human milk (HM) contains a large variety of active immune components [4], which are present in differing concentrations [5], yet no comprehensive study has delved into the influences of maternal characteristics on immune composition of HM. We may expect HM to contain all necessary immunological components in the amounts needed for an appropriate infant immune development.…”