When infants breastfeed, they receive an immune boost that helps them fight off infectious diseases, according to a recent study by Katherine Wander, associate professor of anthropology at Binghamton University.
She is the senior author of “Tradeoffs in Milk Immunity Affect the Risk of Childhood Infectious Diseases”, published in June in Evolution, medicine and public health. Co-authors include Masako Fujita of the Department of Anthropology at Michigan State University, Siobhan Mattison of the Department of Anthropology at the University of New Mexico and the National Science Foundation; and Frida Mowo, Ireen Kiwelu and Blandina Mmbaga in Tanzania, whose associations include the Kilimanjaro Christian Medical Center and the Kilimanjaro Clinical Research Institute. Graduate students from Binghamton University were also part of the research team, with tasks ranging from data collection in Tanzania to data cleaning and analysis. They include Margaret Duris, Megan Gauck, Tessa Hopt, Katherine Lacy, Angela Foligno, Rebecca Ulloa and Connor Dodge.
For the project, the research team studied nearly 100 mother-child pairs in rural Kilimanjaro. Prolonged breastfeeding is the norm in this population and infectious diseases during early childhood are very common, even compared to other parts of East Africa. This makes Kilimanjaro an ideal setting to begin understanding how milk’s immune protection might affect infectious disease risk, Wander said.
“You most often hear about the milk immune system in terms of the transfer of maternal antibodies to infants via the milk – which is probably very important – but it seems there’s a lot more going on as well. The milk immune system is a complete system, capable of mounting immune responses,” Wander said. “We are only beginning to understand the full extent and role of the milk immune system.”
Milk and immunity
Breast milk contains everything needed to mount immune responses, from antibodies to multiple types of immune cells and more. Although they come from the mother’s immune system, these components of milk appear to be conserved rather than randomly selected from the mother’s blood, although this mechanism remains poorly understood, Wander explained.
To test the immune system’s impact of milk on infant health, researchers combined a few milliliters of milk with a small amount of bacteria, then placed the mixture in an incubator overnight. They then measured the increase in interleukin-6, an immune cell communication molecule that promotes inflammation. This in vitro response gives an indication of how the milk’s immune system is likely to react to bacteria encountered in the infant’s body – the gut, for example.
The research team also followed Tanzanian infants to assess whether those given milk that showed stronger immune responses in in vitro tests had a lower risk of infectious diseases. This appears to be the case: infants whose breast milk showed greater responses to Salmonella had fewer infectious diseases, especially respiratory infections such as pneumonia.
But the milk that elicited larger responses to Salmonella also tended to produce stronger responses to a mild strain of E.coli, which is common in the human intestinal tract, and these responses were not beneficial to infants. Infants who received milk which mounted stronger responses to E.coli were at higher risk for gastrointestinal infections. This may indicate that inappropriate milk immune system responses – for example, to bacteria normally present in the gut – may be disruptive. Gut bacteria play an important role in preventing diarrhea and other infectious diseases, the authors note.
While all immune responses have trade-offs, the downside of milk – both immediate and common – was a surprising finding.
“With so much at stake, we really expected the milk immune system to be very finely tuned to protect infants from infection,” Wander said.
The researchers expected to see, at most, negative effects of inappropriate immune responses somewhere down the line, such as slower growth or less than ideal microbial flora. But telling the difference between microbial friend and foe is tricky business, even for mature adult immune systems, as is eliminating an infection without damaging a person’s own tissues. So, the authors say, perhaps they shouldn’t have been surprised to see these trade-offs occur in infants as well.
In addition to reducing the risk of respiratory infection, immune responses from milk can help “train” the infant’s developing immune system to respond to dangerous bacteria. Further research is needed to determine how immune development adapts to inputs, such as experience with infectious diseases, microbial flora, and the immune system in milk.
“These findings are exciting, but the implications for public health and health care will only become clear with further research,” said co-author Mmbaga of the Kilimanjaro Clinical Research Institute. “We need to understand how milk immune responses are affected by factors around which we can design public health programs, such as HIV infection or malnutrition.”
This research may have applications beyond infancy and breastfeeding. Understanding how the immune system evolved to strike a balance between protection and damage could help shed light on health issues, from childhood diarrhea and pneumonia to autoimmune diseases.
“Too often, we implicitly assume that immune responses to distinct stimuli are entirely distinct – as if the immune system’s ability to respond to a dangerous infectious agent had no implications for its ability to tolerate anything beneficial or benign, where the answer is likely to do more harm than good,” Wander noted. “Clients that this is not the case are mounting, however, including this study.