CINCINNATI —A multi-center study led by researchers at Cincinnati Children’s sheds surprising new light on why some newborns become severely ill from Escherichia coli infection, but others do not.
Turns out that most babies are immune because of germ-fighting antibodies they receive from their moms.
The study, published March 11, 2026 , in the prestigious journal Nature , dove into new depths to explore why only some babies develop severe infection to common bacteria. E. coli is a common bacteria 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, PhD , 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 protect 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 1 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 reveal 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, PhD , 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.”
Next Steps
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.
About the Study
Cincinnati Children’s co-authors also include Raymond Diep, Ujjwal Adhikari, Kubra Gokce Tezel, MD, Giang Pham PhD, Allison Burrell, BSN, Mary Staat, MD, MPH, David Haslam, MD, and John Erickson, MD, PhD.
The study also was supported by the Division of Comparative Medicine, Cellular Manipulations Laboratory & Cell Processing Facility, and the Michigan Biotrust for Health, which provided newborn blood specimens.
Funding sources included grants from the National Institute of Allergy and Infectious Diseases (R01AI175431, R01AI189741, R01AI184537, and U01AI144673); the Good Ventures Foundation; the Burroughs Wellcome Fund; the March of Dimes Ohio Prematurity Research Collaborative; and the National Health and Medical Research Council (Australia) (1181958, 2001431, and 2037698).
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About Cincinnati Children’s
Cincinnati Children’s is a nonprofit, comprehensive pediatric health system. As the leader in improving child health, Cincinnati Children’s pushes the boundaries of what’s possible in research, clinical care, education and innovation so that every child can live their best possible life. The organization is consistently named one of the top pediatric hospitals in the nation in U.S. News & World Report ’s list of Best Children’s Hospitals Honor Roll, and is the #3 recipient of pediatric research grants from the National Institutes of Health.
About Children’s Mercy
Founded in 1897, Children’s Mercy is a nationally recognized, independent pediatric health system and a world leader in pediatric translational research committed to transforming the lives of children and families. With hospitals and specialty clinics across Missouri and Kansas, Children’s Mercy delivers world-class, family-centered care closer to home. As a nonprofit organization, Children’s Mercy reinvests every dollar donated into advancing pediatric medicine, supporting innovative research and training the next generation of pediatric specialists. With more than 800 pediatric experts, researchers and faculty we are dedicated to improving outcomes and creating a healthier future for all children. Children’s Mercy has earned repeated recognition from U.S. News & World Report as one of “America’s Best Children’s Hospitals” and is the first health system in Missouri or Kansas to receive six consecutive Magnet designations for nursing excellence. Thanks to generous philanthropic support and a strong volunteer community, Children’s Mercy provides hope, comfort and the prospect of brighter tomorrows to every child who comes through its doors. Visit Children’s Mercy and the Children’s Mercy Research Institute to learn more, and follow us on Facebook, LinkedIn, Instagram, Bluesky and YouTube for the latest news and videos.
About the University of Queensland
The University of Queensland, located in Brisbane, is a top-50 global research-intensive institution and a member of Australia’s prestigious Group of Eight. Ranked #42 in the 2026 QS Rankings, it offers extensive programs in science, health, and engineering to over 55,000 students.
Nature
Experimental study
Not applicable
Natural maternal immunity protects neonates from Escherichia coli sepsis
11-Mar-2026
The authors declare no competing interests.