Antibiotics leave lasting mark on baby immune systems

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Antibiotics save babies’ lives but affect their gut, lungs, and ability to fight infection, researchers report.

University of Rochester Medicine scientists found that early antibiotic exposure disrupts babies’ natural gut bacterial balance and that the disruption “travels” to the lungs, fundamentally rewiring how lung immune cells are programmed and influencing lung repair and the ability to fight infections.

Published in Mucosal Immunology, the research found antibiotic-driven changes shifted newborns’ lung immune cells from offense, where they are primed to respond aggressively to foreign threats, to defense, where they are focused on damage control and repair.

The changes lasted over time and may help explain why children who got antibiotics as newborns sometimes have more respiratory issues as they grow older.

“The research in no way suggests doctors should hesitate to use antibiotics in babies when necessary, as they are one of the most important tools in preventing serious illness and even death,” says senior study author Hitesh Deshmukh, chief of neonatology at University of Rochester Medicine Golisano Children’s Hospital and professor of Pediatrics at the School of Medicine & Dentistry.

“But we’re learning more about how disrupting babies’ gut bacteria in early life can change immune cells in ways that persist long after infancy.”

Antibiotics are extremely common in NICUs and newborn nurseries across the country, and doctors balance the need for antibiotics with their risks. They are very helpful in decreasing infections, but because they wipe out harmful bacteria and good bacteria, they can cause gastrointestinal infections like diarrhea and increase susceptibility to asthma and allergies later in life.

“We hope these findings will ultimately guide new approaches, whether that means protecting the microbiome during antibiotic treatment or developing targeted therapies to support babies whose early immune programming may have been altered,” adds postdoctoral researcher and study author Uday Pandey, a member of Deshmukh’s lab.

Scientists mapped lung immune cells in newborn mice and compared them with adult mice. When they gave antibiotics to newborn mice—like many babies get in the NICU—it changed how the immune cells work. When antibiotics wiped out key gut bacteria, some genes that control how the lungs respond to infection were put into overdrive, while others were dialed way down.

For example, signals that prime cells to kill viruses—critical to protecting babies from infection early in life—subsided. Signals that prioritize repairing damaged tissue, usually seen at higher levels in adults, were ramped up. These changes were not seen in mice with a healthy, undisturbed microbiome.

Most striking to the research team was that the changes didn’t fade with time. Mice that received antibiotics early in life still showed significant differences in their lung immune cells in young adulthood, suggesting the shifts set in motion during the critical newborn window continued through development.

“In babies, the gut microbiota is evolving, so any small changes that happen early on are more likely to get propagated and amplified as time passes,” notes Deshmukh.

Using a large biorepository of donated lung tissue at URochester Medicine Golisano Children’s Hospital, known as LungMAP and run by Gloria Pryhuber, a professor of neonatology, the team confirmed that the findings held true in human lung cells.

At birth, there’s only one immune cell type, called a macrophage, in the lungs. Several other types of immune cells travel from the bone marrow to the lungs after birth, and a newborn’s gut microbiome plays a critical role in this process. The microbiome sends chemical signals that help program the lungs’ specialized immune cells, which behave differently in newborns compared to adults.

“Researchers have known antibiotic-exposed newborns deviate from a normal infant gut, but we are the first to link changes in the microbiome with changes in lung immune cell behavior,” says Deshmukh.

The work adds to a growing body of research being conducted at University of Rochester Medicine and other institutions that demonstrates how the gut microbiome influences many aspects of health, including susceptibility to environmental and food allergies; metabolism, weight, and cardiovascular disease; brain health; and much more.

The bulk of the research was conducted at Cincinnati Children’s Hospital Medical Center, where Deshmukh worked before joining University of Rochester Medicine in 2025. Final studies were completed in Rochester.

The research was funded by the National Institutes of Health.

Source: University of Rochester