Cystic Fibrosis Disrupts Early Gut Development in Infants

Findings from a new Dartmouth-led study, published in the journal mBio, highlight key differences in the gut microbiome (communities of bacteria) of infants with cystic fibrosis (CF) compared to that of healthy infants, and how these alterations may adversely affect their health. CF is a multi-organ genetic disease that causes sticky mucus to build up in the lungs and digestive system, as well as heightened inflammation in the gut and at other body sites.

“It’s been known that in healthy infants, the intestinal microbiome is very dynamic and changes over time as a consequence of how they’re delivered at birth, whether they’re breastfed or not, and when they transition to solid food, among other factors. Then at three to five years of age, these changes stabilize into an adult-like microbiome. This process is key to healthy development,” explains lead author Benjamin Ross, PhD, an assistant professor of microbiology and immunology at Dartmouth’s Geisel School of Medicine.

“We didn’t really know how that process played out in infants with CF, so we set out to study how the gut microbiome of infants with the disease matured and if that maturation process was different compared to healthy kids,” says Ross, whose collaborators at Geisel and Dartmouth Health included George O’Toole, PhD, Juliette Madan, MD, MS, and Julie Sanville, DO.

For their study, the investigators recruited a cohort of 40 infants with CF from the Northern New England area who were cared for and followed at Dartmouth Hitchcock Medical Center between 2009 and 2019. The team used DNA sequencing techniques to analyze the bacterial composition of stool samples of the infants from birth to three years.

They then compared the types of bacteria found in the microbiomes of the local CF infant cohort with those found in healthy infants—which were taken from large, publicly available data sets across the U.S. and in Northern Europe.

“Our major conclusion was that in CF the microbiome really doesn’t change very much, so it’s essentially stunted or delayed in its maturation compared to healthy kids, and this failure to mature may contribute to poor health,” says Ross. “For example, we found a depletion of health-associated bacteria in the CF kids, including Faecalibacterium Prausnitzii, which is a bacterium that specializes in using dietary fiber as an energy source and is known to stimulate anti-inflammatory responses.”

Ross and his colleagues are planning follow-up studies using mouse models to better understand why these alterations in the gut microbiome occur in CF and what the consequences are on health.

“We hope this work can include testing and developing interventions, such as probiotics or dietary changes, that may help mitigate the effect of the disease on the microbiome or supplement it with aspects that will help rescue microbiome deficiencies,” he says.

Reference: Verster AJ, Salerno P, Valls R, et al. Persistent delay in maturation of the developing gut microbiota in infants with cystic fibrosis. mBio. 2025;0(0):e03420-24. doi: 10.1128/mbio.03420-24

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