If a parent contracts an infection while breastfeeding, their body can transmit biological stress signals to the newborn through tiny particles hidden in the breast milk. Recent research has revealed that changing the parental environment to be more engaging and supportive can block these stress signals and protect infants’ developing brains and future behavior. The study was published in the journal Molecular Psychiatry.
Breast milk provides more than just calories and basic nutrition. It contains a wide variety of hormones, immune cells, and microscopic bubbles called extracellular vesicles. These tiny membrane-covered packages act like biological mail carriers. They safely travel through the harsh environment of the infant’s intestines, enter the bloodstream, and drop genetic material into distant tissues.
Inside these vesicles are regulatory molecules known as microRNAs. To understand microRNAs, it helps to examine how cells normally function. DNA acts as a master instruction manual filled with blueprints for keeping your body alive. When cells need to function, they make messenger RNA to convey instructions to cellular factories that build proteins.
MicroRNAs are small pieces of genetic code that act like dimmer switches, binding to messenger RNA and stopping protein construction. Because it pauses the assembly step, this process is known as posttranscriptional regulation. By delivering these microRNAs to the infant, the milk follicles can turn on or off specific cellular functions in the developing body.
Scientists understand that a mother’s illness during pregnancy can affect fetal brain development. Less is known about how infections during postpartum lactation alter the genetic messages passed through breast milk. A team of Julia Martz of the Massachusetts College of Pharmacy and Health Sciences, Bayla Hamer of Touro University, and colleagues set out to investigate this dynamic.
The researchers wanted to see whether a parental immune challenge during breastfeeding would change milk composition enough to change the infant’s brain trajectory. They also wanted to know whether better living conditions could buffer mothers and infants from these biological changes. To test this, the researchers separated lactating rats into two different living environments. Half of the animals lived in standard, simple laboratory cages, and the other half lived in enriched environments with extra space, climbing structures, and toys.
On the 10th day after the puppies were fed, half of the mothers in each breeding group received an injection of a bacterial component known as lipopolysaccharide. This ingredient is derived from Escherichia coli. It does not cause an actual infection, but it tricks the body into thinking it is an intruder, causing temporary irritation and mild discomfort, such as lethargy. Researchers often use this substance. This is because it produces a predictable, uniform immune response without the chaotic fluctuations of a live, replicating pathogen.
The remaining mothers received a harmless saline placebo injection. After two hours, the researchers collected milk from all experimental groups. They used a high-speed centrifuge to isolate extracellular vesicles from milk and sequenced the genetic cargo hidden within them.
The researchers found that the simulated infection significantly altered the composition of the milk. Not only did the fat content of milk decrease, but levels of a stress hormone called corticosterone increased. Beyond basic nutrition, immune challenge also altered the profile of microRNAs packaged in milk follicles.
This effect was primarily seen in mothers kept in standard cages. In these mothers, immune challenge altered dozens of microRNAs compared to healthy controls. A rich environment had a strong protective effect on this outcome. Sick mothers living in complex environments had less significant changes in the genetic cargo of their milk, and the fat content of their milk remained normal.
The researchers then looked at the brains of the nursing puppies, focusing specifically on the hippocampus. The hippocampus is a brain structure located deep in the temporal lobe that largely controls learning, memory, and emotional processing. Similar to the mammary sac, changes in microRNA profiles were observed in the hippocampus of pups nursing from sick mothers in standard housing conditions.
In many cases, the specific microRNAs that changed in the infants’ brains matched those found in breast milk. This overlap suggests that the follicles may reach the brain and deposit instructions, or at least set off a chain reaction that changes the infant’s brain chemistry. Similar to the milk samples, pups suckled by mothers reared in enriched environments largely avoided these widespread genetic changes.
This genetic change had a lasting effect on the animals’ behavior during development. When the puppies grew to adulthood, they underwent behavioral testing. One test involved placing rats in a brightly lit open arena to measure anxiety. Anxious animals tend to hug walls, while more relaxed animals are free to explore their exposed centers.
The second test assessed the extent to which animals preferred interacting with a new, unfamiliar rat rather than an inanimate object. This type of social preference test helps researchers measure sociality and developmental milestones in rodents. Adult pups born to sick standard-reared mothers showed higher levels of anxiety-like behavior in the field and also showed a reduced preference for socializing with other rats.
Abundant living space completely prevented these changes in adult behavior. Mothers in enriched cages experienced exactly the same immune challenge, but their adult offspring behaved exactly like healthy controls. The researchers also noted that maternal stress hormones cannot explain this behavioral relief. Milk corticosterone levels remain high even in well-fed mothers, meaning that protected vesicular cargo is likely a source of behavioral buffers.
The researchers noted that this was a small study, with seven to eight pups per test condition, for a total of about 30 pups. This sample size has some inherent limitations. The composition of milk constantly changes over the natural lactation timeline of any mammal, adapting to the daily needs of a growing infant. In this experiment, we only sampled milk during a narrow period of 2 days in the middle of lactation, so it remains unclear how early or late lactation responds to immune stress.
Another limitation involves the precise physical route of the gene cargo. Although the researchers found matching microRNAs in milk and infant brains, they did not visually track the physical movement of the vesicles. It is quite possible that the milk follicles act indirectly in the body. For example, the vesicles may alter the infant’s gut bacteria, which in turn sends signals that affect the hippocampus.
Future studies will need to use fluorescent markers to precisely track where these maternal vesicles travel within the offspring. Other components of milk, such as structural fats and immune proteins, may also cooperate with microRNAs to shape infant brain development. Separating these microscopic variables requires significant resources and time.
Despite these unanswered questions, the present findings suggest a highly physical link between the caregiver’s environment and the biological quality of care. Supporting caring parents by improving environmental conditions and reducing daily stress may do more than just improve mood. It directly shapes the genetic instructions passed on to the next generation, potentially building more resilient infant brains.
The study, “Investigating milk-derived extracellular vesicles as mediators of maternal stress and environmental interventions,” was authored by Julia Martz, Baila Hammer, Tristen J. Langen, Benjamin N. Berkowitz, Benzion Berkowitz, Jasmyne A. Storm, Jueqin Lu, Deepali Lehri, Sanoji Wijenayake, Jordan Marrocco, and Amanda C. Kentner.
