The immune system helps the gut maintain a healthy balance with microbes, supporting immunity and protecting the body from harmful bacteria. Now, a study in mice shows that antibodies in breast milk “teach” a newborn’s gut immune system to respond appropriately to microbes and maintain intestinal balance without causing unnecessary inflammation.

The findings, published in Science, suggest that antibodies in breast milk are a key regulator of intestinal immune development in early life.

In newborns, breast milk provides antibodies along with nutrients and live bacteria. Studies in mice show that maternal antibodies, more than maternal immune cells, prevent excessive activation of gut immune cells, but the exact ways different types of antibodies work in early life are still unclear.

Meera Shenoy at Fred Hutchinson Cancer Center in Seattle, Washington, and her colleagues investigated how maternal antibodies in breast milk shape early-life gut immunity in mice.

Milk antibodies

Mice pups whose mothers lacked antibodies had higher numbers of certain immune cells in gut lymph nodes after weaning, indicating immune over-activation. 

In newborn mice, breast milk antibodies—especially one type called IgG—play a key role in regulating the gut immune system during the first week of life. Early milk is particularly rich in IgG, and even tiny amounts of IgG during the first week prevented over-activation of gut immune cells after weaning. Other milk components, including IgA antibodies, did not have this effect. 

Exposure to IgG antibodies during the first week of life protected the pups against conditions associated with gut inflammation, such as colitis, and also limited immune overreactions to new food antigens. However, later exposure to these antibodies couldn’t fully prevent immune dysregulation, the researchers found. 

Immune education

Experiments in germ-free mice and mice treated with antibiotics—which lack normal gut microbes—showed that this immune regulation depends on the presence of microbes, but it doesn’t require large changes in overall microbiota composition.

Further tests showed that IgG must bind to gut bacteria to be effective. IgG that bound microbes prevented immune over-activation in mice, while IgG that didn’t bind microbes could not. 

The findings show that maternal IgG in breast milk helps the gut immune system shape the microbiota, strengthen the gut barrier, and restrain inflammation, the researchers say. “Further understanding the maternal-offspring interactions that shape immune education will advance strategies to promote beneficial responses to innocuous microbes and environmental antigens and prevent pathological responses throughout life.”