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Associations between fentanyl exposure, gut microbiome and neurodevelopmental outcomes in preterm infants

Pyone David1, Kaitlyn Oliphant1, Christina Zhou2

  • 1Department of Pediatrics, The University of Chicago, Chicago, IL, USA.

Pediatric Research
|June 23, 2026
PubMed

Insights

Fentanyl exposure in preterm infants alters gut microbiome richness and virulence, leading to potential cognitive impairments later in childhood. This study highlights the gut-brain axis connection in neonatal intensive care unit (NICU) patients.

Area of Science:

  • Neonatal Medicine
  • Microbiome Research
  • Neurodevelopmental Pediatrics

Background:

  • Fentanyl is frequently administered to hospitalized preterm infants.
  • Opioid exposure may impact gut microbiome development and neurodevelopmental outcomes.

Purpose of the Study:

  • To investigate the association between postnatal fentanyl exposure, gut microbiome alterations during NICU stay, and neurodevelopmental outcomes up to age 8.
  • To examine how fentanyl affects fecal microbiome richness, composition, and virulence in preterm infants.

Main Methods:

  • Comparison of preterm infants with and without postnatal fentanyl exposure.
  • Analysis of hospitalization stool samples and neurodevelopmental assessments up to age 8.
  • Examination of associations between fentanyl exposure, microbiome differences, and cognitive scores.

Main Results:

  • Fentanyl exposure correlated with decreased fecal microbiome richness and altered microbial taxa (Actinobacteriota, Bacteroidia).
  • Increased fentanyl exposure was linked to constipation, inflammation-related metabolites, and altered microbial virulence.
  • Higher fentanyl exposure associated with worse cognitive scores at 2 years and intelligence quotient at 3-8 years.

Conclusions:

  • Prolonged postnatal fentanyl exposure in preterm infants is linked to gut microbiome changes (richness, virulence) and subsequent cognitive impairment.
  • Fentanyl-associated microbiome alterations during NICU hospitalization manifest early and predict worse cognitive outcomes in preterm infants.
Abstract

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