Families with a baby in the neonatal intensive care unit (NICU) know all too well the importance of tracking their baby’s growth. Gaining weight is a major milestone on the path to going home. But even with carefully managed nutrition, some babies struggle to grow.
In a recent study, Duke University School of Medicine researchers sought to understand why.
A team led by Duke Neonatologist Noelle Younge, MD, MHS, found evidence that the intestinal microbiome — the bacteria that live in the gut — plays a direct role in slow weight gain and poor growth in extremely preterm infants. By transferring gut bacteria from preterm infants into newborn mice, the researchers found that bacteria from infants who struggled to gain weight impaired growth, while introducing bacteria from infants who grew well prevented those growth problems. The findings, published in JCI Insight in August, suggest that modifying the microbiome could one day help improve growth outcomes for vulnerable infants.
The challenge of growth faltering
Infants born extremely premature — before 27 weeks of pregnancy — are at high risk for postnatal growth faltering, a condition characterized by slow weight gain and poor linear growth despite receiving carefully managed nutrition while in the NICU. Younge said growth faltering is a significant concern because it is linked to developmental delays and neurological problems later in childhood.
This period of development normally occurs while the baby is in the womb, and the baby experiences rapid growth during this time. But when infants are born extremely premature, they miss much of that critical developmental window when adequate growth is particularly important for brain and organ development.
“As neonatologists, we work hard to optimize nutrition in the NICU for these infants, providing them with human milk and fortifying that with additional calories and protein to support their growth and development,” said Younge, the Jean and George W. Brumley, Jr., MD, Associate Professor of Pediatrics. “But, despite that, many of these infants still experience growth faltering.”
Testing the microbiome's influence
In a previous study, Younge found that the microbiomes of extremely preterm infants who experienced growth faltering developed differently from those of infants who had appropriate growth. However, that earlier work could only identify associations, not a direct influence.
To test whether the gut microbiome directly influences growth, in this recent study, Younge and her team transferred bacteria collected from the stool of 10 extremely preterm infants into newborn mice. They then compared growth in mice that received bacteria from infants with growth faltering with growth in mice that received bacteria from infants who grew well.
Mice that received bacteria from infants with growth faltering experienced slower weight gain and poorer postnatal growth than mice that received bacteria from infants who had grown appropriately.
Another notable finding was that growth impairment could be prevented. When the mice that had received bacteria from growth-faltering infants at birth were later treated with bacteria from infants who grew well, the animals did not go on to develop growth faltering.
“This suggests that modifying the microbiome of these infants could be a new approach to prevent growth faltering,” Younge said.
Although her previous study had identified microbiome differences between infants with and without growth faltering, Younge said she was struck by the clarity of the findings in this current study.
“We were surprised to see that there was such a clear impact on growth in this model,” she said. “We knew that the microbiomes had differences in infants with growth faltering, but we thought that might be because these infants were sicker or treated differently in terms of the antibiotics they received. We saw clear differences in this model, where the only thing that we modified between our experimental groups was the microbiome.”
Toward new therapies
The findings also point to potential new approaches for supporting growth in extremely preterm infants. Future approaches could include microbiome-targeted therapies, probiotics, bacterial components, or nutrition strategies designed to support healthy microbiome development.
While probiotics have been used in NICUs to reduce other complications such as necrotizing enterocolitis, a serious gastrointestinal problem, growth-focused microbiome therapies remain an area for future investigation.
Younge recently received NIH funding to continue this line of research. Her team plans to investigate how the microbiome influences growth and metabolism during infancy and to test potential interventions designed to modify the microbiome using the same experimental model.
As a neonatologist, Younge said her research is directly inspired by caring for premature infants and their families and witnessing their struggles firsthand. She is hopeful for what this research may one day mean for them.
“This could eventually lead to the discovery of strategies that could be translated clinically to help these babies thrive in the NICU,” she said. “There's potential to have an impact on not only their short-term outcomes in the NICU, but their long-term developmental outcomes as well.”
Funding: National Institutes of Health, The Zeist Foundation