An Anthropological Lens into Human Milk MicroRNAs: Roles in Evolution and the Epigenetic Programming of Infant Health

epigenetic role in regulating infant gene expression. Most anthropological studies of human milk have focused on the evolutionary and biocultural significance of milk macronutrient content for infant development. This review will focus specifically on the value of studying milk miRNAs, a critical bioactive component of milk that may transmit cues to offspring about maternal environments. These cues could epigenetically program infant development and shape health trajectories throughout the life course. miRNAs are short, single-stranded ribonucleic acids that serve as posttranscriptional regulators of gene expression that can be passed to the infant gut in protective extracellular vesicles. Milk miRNAs tend to vary across lactation stages, with maternal obesity, in response to stress, and because of other conditions, though functional consequences for infants are yet unclear. Milk is rich in immune-related miRNAs along with miRNAs relevant to metabolism, neurodevelopment, cancer, and stress response. Some milk miRNAs have been associated with infant conditions such as colic, asthma, and autism. We discuss the evolutionary relevance of milk miRNAs, focusing on conservation across closely related species and their potential contributions to unique features of human evolution, particularly neural development. We further discuss how they may serve as an important mechanism shaping the evolution of humans and their life history strategies. Study of miRNAs may also be integral to the Developmental Origins of Health and Disease, both being programmed by maternal experience and potentially programming infant outcomes, with a mix of harmful and potentially protective effects. Alongside value for anthropological inquiry, milk miRNAs have important translational ramifications for public health and pediatric medicine, as they may be critical for infant health and development but can be altered under certain environments. They are also significantly reduced in pasteurized donor milk and infant formulas. We end by considering ethical considerations within this emerging field, such as avoiding the pathologization of milk, alongside future directions, including specific research questions and study designs that could address questions of anthropological significance.