Mechanisms affecting the gut of preterm infants in enteral feeding trials: a nested cohort within a randomised controlled trial of lactoferrin

Greg Young, Janet E. Berrington*, Stephen Cummings, Jon Dorling, Andrew K. Ewer, Alessandra Frau, Lauren Lett, Chris Probert, Ed Juszczak, John Kirby, Lauren C. Beck, Victoria L. Renwick, Christopher Lamb, Clare V. Lanyon, William McGuire, Christopher Stewart, Nicholas D. Embleton

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Objective To determine the impact of supplemental bovine lactoferrin on the gut microbiome and metabolome of preterm infants.

Design Cohort study nested within a randomised controlled trial (RCT). Infants across different trial arms were matched on several clinical variables. Bacteria and metabolite compositions of longitudinal stool and urine samples were analysed to investigate the impact of lactoferrin supplementation.

Setting Thirteen UK hospitals participating in a RCT of lactoferrin.

Patients 479 infants born <32 weeks’ gestation between June 2016 and September 2017.

Results 10 990 stool and 22 341 urine samples were collected. Analyses of gut microbiome (1304 stools, 201 infants), metabolites (171 stools, 83 infants; 225 urines, 90 infants) and volatile organic compounds (314 stools, 117 infants) were performed. Gut microbiome Shannon diversity at 34 weeks corrected age was not significantly different between infants in the lactoferrin (mean=1.24) or placebo (mean=1.06) groups (p=0.11). Lactoferrin receipt explained less than 1% variance in microbiome compositions between groups. Metabolomic analysis identified six discriminative features between trial groups. Hospital site (16%) and postnatal age (6%) explained the greatest variation in microbiome composition.

Conclusions This multiomic study identified minimal impacts of lactoferrin but much larger impacts of hospital site and postnatal age. This may be due to the specific lactoferrin product used, but more likely supports the findings of the RCT in which this study was nested, which showed no impact of lactoferrin on reducing rates of sepsis. Multisite mechanistic studies nested within RCTs are feasible and help inform trial interpretation and future trial design.
Original languageEnglish
Number of pages8
JournalArchives of Disease in Childhood: Fetal and Neonatal Edition
Early online date17 Nov 2022
DOIs
Publication statusE-pub ahead of print - 17 Nov 2022

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