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Updated: Jun 17, 2025
Growing a Cystic Fibrosis-Relevant Polymicrobial Biofilm to Probe Community Phenotypes
Published on: April 19, 2024
Premodulator microbiome alterations associated with postmodulator growth outcomes in pediatric cystic fibrosis: Can
Julie Sanville1, George A O'Toole2, Juliette Madan3,4,5
1Department of Pediatrics, Division of Pediatric Gastroenterology, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire, USA.
Insights
Early gut microbiome patterns in children with cystic fibrosis (CF) predict weight status, even with modulator therapy. Specific microbial signatures are linked to an increased risk of being overweight, suggesting potential for early interventions.
Area of Science:
- Microbiome research
- Pediatric health
- Cystic Fibrosis (CF) research
Background:
- The gut microbiota is crucial for childhood growth.
- Children with cystic fibrosis (CF) often experience growth challenges.
- Highly effective modulator therapy is transforming CF care.
Purpose of the Study:
- To identify early gut microbial signatures in children with CF (CwCF) before modulator therapy.
- To associate these premodulator microbial patterns with later childhood weight status.
- To understand the role of the microbiome in growth among CwCF on modulator therapy.
Main Methods:
- Longitudinal stool sample collection from CwCF (13 days to 60 months).
- Metagenomic sequencing to analyze microbial taxa abundance.
- Multivariate regression to link microbiome data with growth metrics (normal weight vs. risk of overweight).
Main Results:
- Significant differences in early microbiome composition were found between normal weight CwCF and those at risk of overweight.
- Early microbiome patterns were stronger predictors of growth status than modulator therapy use.
- Specific taxa like *Eggerthella lentha*, *Ruminococcus*, and *Bacteroides* were less abundant in those at risk of overweight, while *Bacteroides stercoris* was more abundant.
Conclusions:
- The early-life gut microbiome is a strong predictor of growth in CwCF undergoing modulator therapy.
- Identified microbiome signatures can indicate an elevated risk of being overweight.
- Findings suggest potential for microbiome-targeted interventions or nutritional guidance to prevent complications in CwCF.
Objectives:
The gut microbiota plays an important role in childhood growth. Our longitudinal cohort includes children with cystic fibrosis (CwCF) treated with highly effective modulator therapy. We aimed to elucidate early premodulator microbial signatures associated with postmodulator weight for CwCF later in childhood.
Methods:
Stool samples were collected from CwCF at 13 days to 60 months. Metagenomic sequencing determined differentially abundant taxa. Children with body mass index or weight for length Z-scores within 1 standard deviation of the mean (SD) were considered normal weight, those >1 SD were classified as risk of overweight while children <1 SD were considered undernourished, although no CwCF met this latter criterion here. Multivariate regression models were applied to identify significant associations between metadata and microbial taxonomic relative abundances.
Results:
One hundred and eighty-nine stool samples were analyzed from 39 CwCF. We identified statistically significant differences in early microbiome patterns among those at risk of being overweight compared to those who were normal weight when adjusted for age, sex, CF mutation, and early feeding method. Early microbiome was a stronger driver of growth status than current modulator use. Among those at risk of overweight, several taxa that were consistently in lower abundance included Eggerthella lentha, Ruminococcus, Bacteroides, with increase in abundance of Bacteroides stercoris.
Conclusions:
The early microbiome strongly predicts growth in the setting of modulator use for CwCF and we identify microbiome signatures associated with risk of being overweight. We highlight the possibility for interventions or early alternations to nutritional guidance for prevention of comorbid complications.
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