Breastfeeding Challenges May Have Genetic Roots

The delivery room bustles with palpable excitement. With a final push, the room is filled with the cries of a newborn baby. After a quick medical assessment, the infant settles in for her first ever meal—breast milk. Not only does breast milk contain all the nutrients that babies need in the first six months of their lives, but it also provides essential antibodies that protect the tiny humans from infections and boost their immunity.¹ Studies over the past few decades suggest that breastfed infants have a lower risk of diarrhea, sudden infant death syndrome, asthma, and childhood infections.²

Given these benefits, the World Health Organization recommends exclusive breastfeeding for the first six months of life, continuing up to two years or longer along with other foods. However, as of 2021, only 48 percent of six-month-old infants worldwide were breastfed exclusively. One of the main reasons mothers can’t breastfeed for the recommended time is insufficient milk production. Thirty-five percent of individuals who stop breastfeeding early report this as the cause.³ Often, excessive lactation can also lead to early weaning because of higher chances of breast pain, clogged milk ducts, and tissue inflammation. Yet, studies investigating the molecular mechanisms underlying these conditions are sparse.

Now, researchers from the University of California, San Francisco (UCSF) have analyzed cells in breast milk samples from humans to identify how changes in gene expression could influence milk production.⁴ Their findings, published in Science Advances, could help researchers identify specific genes that promote or suppress milk production and pave the way for better diagnosis and treatment of breastfeeding problems.

To analyze molecular markers associated with varying levels of milk production, Nadav Ahituv, a human geneticist at UCSF and coauthor of the study, and his team collected fresh milk samples from 30 lactating individuals: nine with low production, seven with high production, and 14 with normal production. Breast milk is composed of different types of cells, such as immune cells, epithelial cells, and stem cells, along with milk fat globules. The team evaluated the RNA sequences of these cells and fat globules, and they observed that various genes showed altered expression in the low- and high-production groups, compared to normal. A quantitative PCR-based analysis of a few candidates revealed that some people with low milk supply had higher expression of Perilipin 4 (PLIN4), a gene associated with lipid accumulation in other tissues and with breast cancer, and glucagon-like peptide-1 receptor (GLP1R), the well-known gene associated with glucose homeostasis, compared to those with normal or high production. On the other hand, high milk producers often had elevated levels of Krüppel-like factor 10 (KLF10), a gene implicated in mammary gland development and function.

Individuals who stop breastfeeding earlier than expected often supplement the child’s diet with infant formula. Ahituv and his team wanted to understand how varying levels of breast milk supply and formula affected the infant microbiome diversity. They analyzed 20 stool samples from ten infants of participants with low and normal milk production and 16 samples from their mothers. This group also included infants who were fed formula. The researchers observed higher microbiome diversity in infants who were nursed by low milk producers, compared to normal producers, which they speculated could be due to formula supplementation. Scientists have previously shown that formula feeding stimulates changes in the infant gut microbiota that are associated with an increase in obesity risk.⁵ Considering this, Ahituv and his colleagues emphasized that their findings support the idea that individuals with low milk production should continue partial breastfeeding to encourage the development of a healthy infant gut microbiome.