Mothers’ exposure to microbes protects their newborn babies against infection

A multi-center study led by researchers at Cincinnati Children’s sheds new light on why some newborns become severely ill from Escherichia coli infection, but others do not. It turns out that most babies are immune because of germ-fighting antibodies they receive from their moms.

The study, published, in Nature, explored why only some babies develop severe infection to common bacteria. E. coli is a common bacterium that lives in the intestines of nearly all people and is a leading cause of severe infection in newborn babies. The research revealed that the babies that became most severely ill from E. coli infections also had markedly lower levels of germ-fighting antibodies transferred from their mothers.

“This helps explain a long-standing question: if most babies are exposed to germs soon after birth, why don’t even more develop severe infection?” says senior author Sing Sing Way, MD, Ph.D., an expert on how the immune system changes in expecting mothers and babies in the Division of Infectious Diseases at Cincinnati Children’s.

“Our findings provide a key missing piece to this puzzle—the antibodies stimulated by the presence of these common bacteria in our intestines protect us against infection. In pregnancy, the natural transfer of these germ-fighting antibodies from mothers to babies in the womb protects the vast majority against infection. In the rare situation when these antibodies are low in mothers or inefficiently transferred, babies are at much higher risk for infection.”

Exploring why most babies avoid infection

Scientists have long known that newborns are naturally more vulnerable to infection, in large part because their immune systems have not had time to fully mature.

Pediatricians also have known that E. coli is among the most common causes of infection that babies face. Interestingly, however, despite almost all babies being exposed to E. coli shortly after birth, severe infection occurs only in about one in every 1,000 live births. This discordance prompted the research team to investigate why numbers of babies with severe illnesses weren’t even higher.

Centers team up to study real-world samples

The research involved a collaboration among investigators at Cincinnati Children’s, the University of Queensland in Australia, University of Texas Southwestern Medical Center, Children’s Mercy Kansas City and the University of Missouri Kansas City School of Medicine.

To conduct the study, researchers retrieved dried blood samples collected for routine newborn screening from 100 babies that eventually developed E. coli infection. They compared the antibody levels found in those samples to hundreds of other infants that did not develop infection.

The analysis revealed that antibodies targeting E. coli were consistently reduced in infected babies. Since E. coli can show a lot of variability, a panel of strains isolated from infected babies were used to evaluate the levels of these germ-fighting antibodies.

Mouse studies suggest how to improve protection

Mice used in research are often purposefully raised without any exposure to potential germs, including E. coli, and therefore lack these germ-fighting antibodies.

Using such mice, the research team found that introducing a probiotic strain of E. coli, called Nissle 1917, to mice before pregnancy stimulates production of protective antibodies that efficiently protect newborn mice against infection. This probiotic is widely available for human use in Europe, Asia and Australia under the trade name Mutaflor.

“Understanding protection takes both types of evidence—what we can evaluate from specimens in human babies that naturally develop infection, and what we can test by experimentally causing infection,” says co-author Mark Schembri, BSc, Ph.D., from the Institute for Molecular Bioscience at The University of Queensland in Australia.

“By strategically combining real-world human newborn screening samples with carefully designed infection models, we can start to pinpoint which antibody targets matter most and how broad protection might be achieved.”

Co-author Susana Chavez-Bueno, MD, of Children’s Mercy Hospital in Kansas City, adds, “Neonatal sepsis can escalate quickly, and clinicians need better ways to identify which infants are at highest risk. These findings suggest a path toward earlier risk recognition and eventually, prevention strategies built around restoring the missing protective maternal antibodies.”

Looking forward, the co-authors say they plan to develop a screening test to identify newborns at highest risk of severe E. coli infection, and eventually a safe-for-mothers probiotic that could strengthen their own immunity as well as immunity transferred to their babies.