Variation among populations in the immune protein composition of mother's milk reflects subsistence pattern

Abstract

Lay summary: Adaptive immune proteins in mothers' milk are more variable than innate immune proteins across populations and subsistence strategies. These results suggest that the immune defenses in milk are shaped by a mother's environment throughout her life.

Background and objectives: Mother's milk contains immune proteins that play critical roles in protecting the infant from infection and priming the infant's developing immune system during early life. The composition of these molecules in milk, particularly the acquired immune proteins, is thought to reflect a mother's immunological exposures throughout her life. In this study, we examine the composition of innate and acquired immune proteins in milk across seven populations with diverse disease and cultural ecologies.

Methodology: Milk samples (n = 164) were collected in Argentina, Bolivia, Nepal, Namibia, Philippines, Poland and the USA. Populations were classified as having one of four subsistence patterns: urban-industrialism, rural-shop, horticulturalist-forager or agro-pastoralism. Milk innate (lactalbumin, lactoferrin and lysozyme) and acquired (Secretory IgA, IgG and IgM) protein concentrations were determined using triple-quadrupole mass spectrometry.

Results: Both innate and acquired immune protein composition in milk varied among populations, though the acquired immune protein composition of milk differed more among populations. Populations living in closer geographic proximity or having similar subsistence strategies (e.g. agro-pastoralists from Nepal and Namibia) had more similar milk immune protein compositions. Agro-pastoralists had different milk innate immune protein composition from horticulturalist-foragers and urban-industrialists. Acquired immune protein composition differed among all subsistence strategies except horticulturist-foragers and rural-shop.

Conclusions and implications: Our results reveal fundamental variation in milk composition that has not been previously explored in human milk research. Further study is needed to understand what specific aspects of the local environment influence milk composition and the effects this variation may have on infant health outcomes.

Keywords: SIgA; human milk; lactoferin; maternal ecology; milk immunofactors.

Figure 1.

Milk immune protein concentrations visualized for all participants. This heatmap shows the relative protein concentrations for all individuals. Each column is an individual and each row is a protein (LA, lactalbumin; LF, lactoferrin; LZ, lysozyme; SIgA, Secretory Immunoglobulin A; IgG, Immunoglobulin G; IgM, Immunoglobulin M). Shading represents individual’s value as a z-score above (more yellow) or below (more purple) the mean for that protein across all individuals in the study

Figure 2.

Between-group principal components analysis plots. The four plots display a visualization of the between-group principal components analysis used to create a composite measure of the composition of innate (top row) or acquired (bottom row) immune proteins for each population (left column) or subsistence group (right column). The shaded area depicts the convex hull for each population or subsistence group