What breast milk reveals about a child’s future (and mother’s past)

For the first time, we are applying the science of epigenetics to lactation and the results have been truly fascinating. In ancient times, they believed that milk was just “purified menstrual blood” (Galen, 2nd century CE). By 19th century, chemical analysis of human milk began, eventually leading to production of formula milk during the industrial revolution. Today we have reached a new frontier. We can now demonstrate that milk carries epigenetic signatures of maternal life experiences, and these signatures might even shape the child’s  behavior, all through lactation. 

In the current study, we researched 103 mothers and their babies. We analyzed the composition of their milk – focusing on fatty acids and tiny epigenetic regulators called microRNA that modulate gene activity at the post-transcriptional level. We compared women with varying levels of adverse childhood experiences. Our results clearly show that the milk of women who experienced a higher number of adverse or traumatic events in childhood contained higher levels of certain microRNAs. Seeing such a robust correlation between the number of traumatic events and milk miRNAs was exciting and disturbing at the same time. But even more startling was the correlation of milk microRNAs with offspring behavior. These changes correlated with infant temperament traits already at 5 and 12 months of age. Judging by the functions of the microRNAs altered in the milk, one wonders if there could be consequences on the metabolic health of these children too- an aspect we are aiming to study. 

Such findings could only emerge from a study that brought together expertise from very different fields — and, as it turned out, from a collaboration sparked by a single research paper and a timely email. The study was conducted by two research laboratories with varying expertise, which decided to join forces for this novel study. We synergized advanced molecular analysis of human milk samples with psychological assessment of participating nursing mothers and their babies. The collaboration started when a research paper from Anna Ziomkiewicz’s group “Traumatized women’s infants are bigger than children of mothers without traumas”, caught the attention of TREND Lab PI, Ali Jawaid. He reached out to ask whether any milk samples were available for microRNA analyses. Despite the COVID-19 pandemic sweeping across the world, TREND Lab teammates drove across Poland by car to collect this precious material and deposit it safely in their laboratory. 

The biggest technical hurdle of the study was establishing the protocol enabling us to extract microRNAs from the lipid fraction of milk without losing any drop of it. Therefore, we decided to first test our protocols on unpasteurized cow’s milk bought from the farmers’ market. It worked perfectly and we could promptly proceed with extraction from human samples, sequencing and downstream analyses.

Still, working with biological samples  is much easier than working with actual tiny humans! Studying such an extraordinary group as nursing mothers and their babies is very exciting but sometimes also extremely challenging. The first visits by the mothers and their 5 months old babies  went quite smoothly, thanks to the colorful cozy ambience of our milk collection unit in Wroclaw. But as they say “little kids, little problems; big kids, big problems”. When the mothers and babies returned, this time babies about to celebrate their first birthdays, they already had learnt to escape from all measuring scales. We had to improvise by rearranging furniture and keeping them calm and somehow, we managed. 

And it has all been worth it. When our PIs started their PhD journeys, the hypothesis that traumatic stress in the parents could impact the health of the offspring via biological pathways was met with much skepticism.  Fast forward thirteen years,  and now we have a potential non-invasive biomarker that can predict intergenerational transmission of trauma effects. This feels very rewarding. These findings open up new avenues for early-life interventions. If certain microRNAs in milk can signal maternal stress history, one day we might be able to use a simple milk sample to identify children at higher risk of stress-related developmental challenges — and support both mothers and infants earlier. Our work also adds to a growing recognition that mental health is not just important for the mother but have biologically embedded consequences for the next generation.

And what’s next for our research? We certainly have to prove causality for the role of milk miRNAs as direct determinants of offspring health. And we need cross-fostering studies in rodent models for that. In German there is a saying: “Das ist zum Mäusemelken!” – literally, “That’s enough to make you want to milk mice!” – used for things that are impossibly difficult. Well, that’s exactly what we are learning to do now!