Non-invasive faecal cytokine and microbiome profiles predict commencement of necrotizing enterocolitis in a proof-of-concept study

Christian Zenner, Lisa Chalklen, Helena Adjei, Matthew J. Dalby, Suparna Mitra, Emma Cornwell, Alexander G. Shaw, Kathleen Sim, J. Simon Kroll, Lindsay J. Hall

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Abstract

Background & Aims: Necrotizing enterocolitis (NEC) is a life-threatening disease, and the most common gastrointestinal emergency in premature infants. Accurate early diagnosis is challenging. Modified Bell’s staging is routinely used to guide diagnosis, but early diagnostic signs are non-specific, potentially leading to unobserved disease progression, which is problematic given the often rapid deterioration observed. We investigated faecal cytokine levels, coupled with gut microbiota profiles, as a non-invasive method to discover specific NEC-associated signatures that can be applied as potential diagnostic markers.  

Methods: Premature babies born below 32 weeks of gestation were admitted to the 2-site neonatal intensive care unit (NICU) of Imperial College hospitals (St. Mary’s or Queen Charlotte’s & Chelsea) between January 2011 and December 2012. During the NICU stay, expert neonatologist grouped individuals by modified Bell’s staging (healthy, NEC1, NEC2/3) and faecal samples from diapers were collected consecutively. Microbiota profiles were assessed by 16S rRNA gene amplicon sequencing and cytokine concentrations were measured by V-Plex multiplex assays.  

Results: Early evaluation of microbiota profiles revealed only minor differences. However, at later time points, significant changes in microbiota structure were observed for Bacillota (adj. p=0.0396), with Enterococcus being the least abundant in Bell stage 2/3 NEC. Evaluation of faecal cytokine levels revealed significantly higher concentrations of IL-1α (p=0.045), IL-5 (p=0.0074), and IL-10 (p=0.032) in Bell stage 1 NEC compared to healthy individuals.  

Conclusions: Differences in certain faecal cytokine profiles in patients with NEC indicate their potential use as diagnostic biomarkers to facilitate earlier diagnosis. Additionally, associations between microbial and cytokine profiles contribute to improving knowledge about NEC pathogenesis.
Original languageEnglish
Pages (from-to)666-675
Number of pages10
JournalGastro Hep Advances
Volume2
Issue number5
Early online date7 Mar 2023
DOIs
Publication statusPublished - 2023

Keywords

  • Cytokines
  • Gut Microbiota
  • Necrotizing Enterocolitis
  • Noninvasive Biomarkers
  • Preterm Infants

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