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Effect of Hyaluronic Acid 35 kDa on an In Vitro Model of Preterm Small Intestinal Injury and Healing Using Enteroid-Derived Monolayers
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Supplementation with long-chain polyunsaturated fatty acids to extremely preterm infants associates with development

Hanna Danielsson1,2,3, Theo Portlock1,4, Ann Hellström5

  • 1Centre for Translational Microbiome Research, Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet, Stockholm, Sweden.

Pediatric Research
|July 15, 2026
PubMed

Insights

Arachidonic acid (AA) and docosahexaenoic acid (DHA) supplementation impacts the gut microbiome in extremely preterm infants. While this supplementation may influence retinopathy of prematurity (ROP) risk, causality remains undetermined.

Area of Science:

  • Neonatal Medicine
  • Microbiome Research
  • Nutritional Science

Background:

  • Supplementation with arachidonic acid (AA) and docosahexaenoic acid (DHA) is known to reduce severe retinopathy of prematurity (ROP) risk in extremely preterm infants.
  • The role of AA:DHA supplementation in the developing gut microbiome and its potential contribution to ROP protection requires further investigation.
  • Evaluating additional factors influencing microbiome maturation is crucial for understanding infant gut development.

Purpose of the Study:

  • To investigate the impact of AA:DHA supplementation on the gut microbiome composition and function in extremely preterm infants.
  • To explore the potential link between AA:DHA supplementation, gut microbiome changes, and the protective effect against severe ROP.
  • To identify other covariates that influence the maturation of the infant gut microbiome.

Main Methods:

  • Utilized shotgun metagenomics to analyze longitudinal gut microbiome profiles and bacterial gene pathways in 75 extremely preterm infants.
  • Integrated serum protein expression data, quantified via proximity extension assays, with microbiome data.
  • Conducted a randomized clinical trial to assess the effects of AA:DHA supplementation.

Main Results:

  • AA:DHA supplementation was associated with an increased relative abundance of Citrobacter koseri and alterations in protein and metabolic pathways.
  • Severe ROP occurrence correlated with microbiome alpha diversity (Shannon, Evenness) and beta diversity (Bray-Curtis).
  • Study center and gestational age at birth were identified as significant factors influencing microbiome composition.

Conclusions:

  • AA:DHA supplementation demonstrably impacts the gut microbiome in extremely preterm infants.
  • The current study could not establish a definitive causal relationship between AA:DHA supplementation, microbiome alterations, and ROP reduction.
  • These findings underscore the intricate interaction between nutritional interventions, the gut microbiome, and infant development.
Abstract

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