study reveals dynamics of breast milk production | MIT News

For the first time, researchers at MIT have performed a large-scale, high-resolution study of breast milk cells, allowing them to track changes in these cells over time in nursing mothers.

By analyzing human breast milk produced between three days and almost two years after delivery, the researchers were able to identify a variety of changes in gene expression in cells of the mammary gland. Some of these changes were related to factors such as hormone levels, illness of the mother or baby, the mother starting birth control and the baby starting daycare.

“We were able to take this very long view of lactation that other studies haven’t really taken, and we’ve shown that milk changes throughout lactation, even after years of milk production,” says Brittany Goods, former MIT. postdoc who is now an assistant professor of engineering at Dartmouth College and a lead author of the study.

The researchers hope their findings will lay the groundwork for more in-depth studies of how breast milk changes over time. Such studies could eventually lead to new ways to increase mothers’ milk supply or improve the composition of infant formula.

Bonnie Berger, Simons Professor of Mathematics at MIT and head of the Computing and Biology Group at the Computer Science and Artificial Intelligence Laboratory (CSAIL), is one of the study’s lead authors, as is Alex Shalek, Professor associate degree in chemistry at MIT. and Fellow of the Institute for Medical Engineering and Science (IMES); the Koch Institute for Integrative Cancer Research; the Ragon Institute of MGH, MIT and Harvard; and the Broad Institute of Harvard and MIT.

MIT graduate student Sarah Nyquist is the lead author of the paper, which appears this week in the Proceedings of the National Academy of Sciences.

Cellular changes

Human mammary glands can produce more than a liter of milk per day, for months or years after childbirth. Studying how mammary gland cells accomplish this feat has been difficult in humans because the tissue itself cannot be biopsied or otherwise accessed during lactation. However, recent studies have shown that breast milk contains many mammary gland cells, providing a non-invasive way to study these cells.

For this study, the MIT team collected breast milk samples from 15 nursing mothers. Each donor provided samples at multiple time points, ranging from three to 632 days postpartum. The researchers also collected information on health and lifestyle changes that occurred throughout the lactation period.

The researchers isolated more than 48,000 cells from 50 samples and analyzed them using single-cell RNA sequencing, a technology that can determine which genes are being expressed in a cell at any given time. This analysis revealed 10 cell types – one population of fibroblast cells, two types of epithelial cells and seven types of immune cells.

More than half of the immune cells they found were macrophages. These cells appear to express genes that help make the mammary gland more tolerant of the milk proteins they produce, so they don’t trigger an immune response. The researchers also found populations of B cells, T cells and other immune cells, but their numbers were too small to perform in-depth studies of their functions.

By far the most abundant cells they found were lactocytes, which are a type of epithelial cell. These cells expressed many genes for proteins found in breast milk, such as lactalbumin, as well as the transporters necessary for the secretion of milk proteins, micronutrients, fats and other components of breast milk.

Among the lactocytes, the researchers identified a group of cells that appears to be the primary milk producer and another that plays more of a structural role in the mammary gland. Each of these cell types could be further divided into further subtypes, which the researchers hypothesized could be specialized for particular roles.

Over time, the researchers found that the proportion of lactocytes involved in milk production decreased, while the proportion involved in structural support increased. At the same time, genes involved in the response to the hormone prolactin became more active in milk-producing lactocytes but fell in structural lactocytes. The researchers hypothesize that these changes could be linked to the changing nutritional needs of infants as they grow.

“This study, along with other studies that exist, paves the way for mapping and better understanding some of the pathways these cells use to accomplish the enormous amount of work they do,” Goods says.

Composition of milk

Researchers have also found links between the composition of cells in breast milk and events such as babies starting daycare, formula feeding, or the mother starting to use a hormonal contraceptive.

“There are clearly changes in the composition of breast milk that are linked to these lifestyle and health changes, such as childhood illnesses or maternal hormonal contraception,” Nyquist says. “These changes in lactation don’t necessarily have a positive or negative impact on anyone’s health, but they do occur and may give us a better understanding of how breast epithelial cells produce milk and the types of components they can produce.”

The researchers now hope to conduct larger studies that could help them find stronger links between environmental factors and milk composition, and also learn more about how milk naturally changes over time. This could eventually help scientists design better infant formulas or create formulas tailored to different stages of infancy. Researchers also hope to find ways to help breastfeeding mothers increase their milk supply or slow it down when weaning babies.

Further follow-up studies may explore how pumping affects milk composition and breast health, or how to prevent conditions such as mastitis.

“By building this very high-resolution understanding of lactational diversity over time, it not only gives us a way to understand lactation, but it also gives us a set of data and tools to be able to design better solutions to improve the quality of life of mothers, especially when breastfeeding,” says Goods.

The research was funded by the Koch Institute Supporting (Core) Grant from the National Cancer Institute, the National Institutes of Health, a National Research Service Award Postdoctoral Fellowship, the Beckman Young Investigator Program, a Sloan Fellowship in Chemistry, the Charles E. Reed Faculty Initiative, a National Science Foundation Graduate Research Fellowship, an MIT-GSK Gertrude B. Elion Postdoctoral Fellowship, the Columbia University Office of the Provost, the Weizmann Institute of Science National Postdoctoral Award Program for Advancing Women in Science, the International Society for Research in Lactation and Breastmilk Trainee Transition Fund, and the Human Frontier Science Program.

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