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Background <p>Fentanyl, an opioid medication commonly given to hospitalized preterm infants, may alter gut microbiome development and subsequent neurodevelopmental outcomes.</p> Methods <p>We compare a cohort of preterm infants with and without postnatal fentanyl exposure, using their hospitalization stool samples and neurodevelopmental outcomes. The study examines the association between fentanyl exposure, fecal microbiome differences during NICU stay, and neurodevelopmental outcomes up to age 8.</p> Results <p>Fentanyl exposure during NICU hospitalization is associated with a decrease in fecal microbiome richness, negative association with the microbial taxa <i>Actinobacteriota</i> and <i>Bacteroidia</i>, increase in constipation, an increase of microbiome derived metabolites involved in inflammation and gastrointestinal (GI) homeostasis, and altered microbial virulence (i.e. factors that contribute to pathogenicity). Increased fentanyl exposure is associated with worse cognitive scores on the Bayley Scales of Infant and Toddler Development at 2 years of age and the intelligence quotient composite score on the Wechsler Preschool and Primary Scale of Intelligence at 3–8 years of age. Virulence factors present in the microbiome mediated the association between fentanyl and cognitive outcomes at 2 years old.</p> Conclusion <p>Increased duration of postnatal fentanyl exposure in preterm infants is associated with gut microbiome differences (i.e. richness and virulence) and later cognitive impairment.</p> Impact <p><UnorderedList Mark="Bullet"> <ItemContent> <p>Postnatal fentanyl exposure of premature infants in the neonatal intensive care unit is associated with microbiome differences that manifest during their hospital stay.</p> </ItemContent> <ItemContent> <p>Fentanyl-associated microbiome differences during hospitalization include differences in fecal richness, microbial taxa composition, gastrointestinal transit time, microbiome-derived metabolites, and microbial virulence.</p> </ItemContent> <ItemContent> <p>Early gut fentanyl-associated microbiota differences are associated with worse cognitive outcomes in preterm infants at 2–8 years old.</p> </ItemContent> </UnorderedList></p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月23日

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  • Pyone David,
  • Kaitlyn Oliphant,
  • Christina Zhou,
  • Allen Wang,
  • Bree Andrews,
  • Patricia Byrne-Bowens,
  • Anson Zhu,
  • Devon Lewis,
  • Wilfredo Cruz Ayala,
  • Sarah Mohammad,
  • Yueyue Yu,
  • Dinanath Sulakhe,
  • Mark D’Souza,
  • Erika C. Claud

摘要

Background

Fentanyl, an opioid medication commonly given to hospitalized preterm infants, may alter gut microbiome development and subsequent neurodevelopmental outcomes.

Methods

We compare a cohort of preterm infants with and without postnatal fentanyl exposure, using their hospitalization stool samples and neurodevelopmental outcomes. The study examines the association between fentanyl exposure, fecal microbiome differences during NICU stay, and neurodevelopmental outcomes up to age 8.

Results

Fentanyl exposure during NICU hospitalization is associated with a decrease in fecal microbiome richness, negative association with the microbial taxa Actinobacteriota and Bacteroidia, increase in constipation, an increase of microbiome derived metabolites involved in inflammation and gastrointestinal (GI) homeostasis, and altered microbial virulence (i.e. factors that contribute to pathogenicity). Increased fentanyl exposure is associated with worse cognitive scores on the Bayley Scales of Infant and Toddler Development at 2 years of age and the intelligence quotient composite score on the Wechsler Preschool and Primary Scale of Intelligence at 3–8 years of age. Virulence factors present in the microbiome mediated the association between fentanyl and cognitive outcomes at 2 years old.

Conclusion

Increased duration of postnatal fentanyl exposure in preterm infants is associated with gut microbiome differences (i.e. richness and virulence) and later cognitive impairment.

Impact

Postnatal fentanyl exposure of premature infants in the neonatal intensive care unit is associated with microbiome differences that manifest during their hospital stay.

Fentanyl-associated microbiome differences during hospitalization include differences in fecal richness, microbial taxa composition, gastrointestinal transit time, microbiome-derived metabolites, and microbial virulence.

Early gut fentanyl-associated microbiota differences are associated with worse cognitive outcomes in preterm infants at 2–8 years old.