Mouse study reveals new protective benefit of breast milk

An immune component of breast milk known as the complement system shapes the intestinal environment of infant mice in a way that makes them less susceptible to certain pathogenic bacteria, according to a study led by researchers at the Johns Hopkins Bloomberg School of Public Health .

Researchers found that pups fed from lactating mice whose breast milk lacked a key complement protein had different populations of gut microbes than pups fed standard mouse breast milk, making them very vulnerable to Citrobacter rodentium, a bacteria that infects the intestines of mice. . Citrobacter rodentium is similar to certain types of E. coli bacteria that cause diarrhea and can infect humans but not mice.

The researchers’ experiments suggest that the complementary components of mouse breast milk improve the health of infants by directly eliminating certain types of gut bacteria. This remodeling of the intestinal microbiota makes infants much less susceptible to Citrobacter rodentium infection, thus protecting young people from certain infectious threats. Remodeling activity does not depend on antibodies, unlike how complement components are generally thought to function.

Researchers also confirmed in separate in vitro analyzes that breast milk contains these complement components, which demonstrated similar activity in targeting specific bacteria.

Taken together, these findings shed light on the mechanisms by which breast milk functions to provide protection against certain bacterial infections.

The study was published online January 18 in the journal Cell.

“These results reveal the essential role of breast milk complement proteins in shaping the intestinal microbial compositions of offspring and in protecting against bacterial intestinal infections early in life,” explains the lead author of the study. study, Fengyi Wan, Ph.D., professor in the Bloomberg School Department. of biochemistry and molecular biology. “This represents an important expansion of our understanding of the protective mechanisms of breast milk.”

The first author of the study is Dongqing Xu, Ph.D., an assistant researcher in Wan’s research group.

Breastfeeding has many known and suspected benefits. It provides excellent nutrition to infants and appears to protect against certain illnesses in the short or long term. Breast milk is also known to help protect against common infections by sharing the mother’s antibodies and white blood cells.

Breast milk also contains complementary proteins that can work with or “complement” antibodies to attack bacteria. While the complement proteins that circulate in the blood have been the subject of much research, the complement proteins found in breast milk have been studied much less and, until now, their role is unclear.

In the new study, Wan and his team used genetically modified mice lacking essential complement genes. They found that milk from such female mice made weeks-old pups, even those with normal complement genes, highly susceptible to the often fatal colitis caused by Citrobacter rodentium infections. In contrast, puppies fed normal supplement-containing milk showed only minor, transient signs of intestinal infection.

The team discovered that this protective effect of breast milk complement proteins depends on their ability to shape the infant’s gut microbiota. Complement proteins kill certain intestinal bacterial species, and this elimination of microbes creates an overall intestinal environment in which harmful inflammation is much less likely in the presence of Citrobacter rodentium.

“The gut microbiota is of great importance for health,” explains Wan. “Breast milk complement proteins crucially contribute to the establishment of a ‘protective’ gut microbiota during early stages of development, thereby promoting infant health and defending against pathogens.”

The study also appears to mark a breakthrough in fundamental immunology. Complementary proteins found in the blood, although known to be capable of causing direct damage to bacterial cells, are generally thought to work in partnership with antibodies in a specific immune response. However, Wan and his team showed that this activity of breast milk complement against bacteria does not require antibodies and is a nonspecific immune response.

“This opens the door to much new research, for example elucidating the specific biology of complement in breast milk and comparing it to the biology of complement in blood, and assessing the role of complement beyond the specific immune system dependent on antibodies,” Wan said. said.